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[null,null,null,null,null,null,null,"V9 update:"]
[null,null,null,null,null,null,null,"*Add a new button in Summary tab to synchronize results between Results and Summary tabs"]
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[null,null,null,null,null,null,null,"V8 update:"]
[null,null,null,null,null,null,null,"*Added judgement-level comment in the summary table"]
[null,null,null,null,null,null,null,"*Removed \"Double click on this column…\" label in the comments after enter"]
[null,null,null,null,null,null,null,"*Corrected spelling mistakes"]

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["Basic information",null,null,null,null,null,null,null,null,null,null,null,null,"Domain 1. Randomization process",null,null,null,null,null,null,null,null,null,"Domain 2. Deviations from intended interventions",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Domain 3. Mising outcome data",null,null,null,null,null,null,null,null,null,null,null,null,"Domain 4. Measurement of the outcome",null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Domain 5. Selection of the reported result",null,null,null,null,null,null,null,null,null,null,"Domain 6. Overall Bias"]
["Time","Unique ID","Assessor","Study ID","Reference","Experimental","Comparator","Outcome","Results","Aim","Effect of adhering to intervention?","Weight","Sources","1.1","1.2","Note for 1.1&1.2","1.3","Note for 1.3","1.0 Algorithm result","1.0 Assessor's Judgement","1.0 General note","1.0 Optional Question","1.0 Note for optional question","2.1","2.2","Note for 2.1&2.2","2.3","Note for 2.3","2.4","Note for 2.4","2.5","Note for 2.5","2.6","Note for 2.6","2.7","Note for 2.7","2.0 Algorithm result","2.0 Assessor's Judgement","2.0 General Notes","2.0 Optional Question","2.0 Note for optional question","3.1","Note for 3.1","3.2","Note for 3.2","3.3","Note for 3.3&3.4","3.4","Note for 3.4 (not use)","3.0 Algorithm result","3.0 Assessor's judgement","3.0 Gerenal notes","3.0 Optional Question","3.0 Note for optional question","4.1","Note for 4.1","4.2","Note for 4.2","4.3","Note for 4.3","4.4","Note for 4.4&4.5","4.5","Note for 4.5 (not use)","4.0 Algorithm result","4.0 Assessor's Judgement","4.0 General note","4.0 Optional Question","4.0 Note for optional question","5.1","Note for 5.1","5.2","Note for 5.2","5.3","Note for 5.3","5.0 Algorithm result","5.0 Assessor's Judgement","5.0 General note","5.0 Optional Question","5.0 Note for optional question","Algorithm's overall Judgement","Assessor's overall Judgement","6.0 General Note","6.0 Optional Question","6.0 Note for optional question"]
["2021/10/26 12.04",1,"JE","ACCORD","ACCORD 2010","Low targets","Standard targets","total mortality","RR=1.23","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","PY","Y","An internet-based, web browser randomization procedure was employed","N","Described in Table 1 of the main article","Low","Low","An internet-based, web browser randomization procedure was employed.",null,null,"Y","Y","This is an unmasked open trial","NI",null,"NA",null,"NA",null,"Y","Analyses of primary and secondary outcomes were performed with the use of time-to-event methods according to the intention-to-treat principle (Methods section, N Engl J Med 2010;362:1575-85).","NA",null,"Some concerns","Some concerns","This is an unmasked open trial.",null,null,"Y","patients lost to follow-up in study groups were 29/2362 vs  29/2371 (NEJM 2010;362:1575-85).","NA",null,"NA",null,"NA",null,"Low","Low","No signifficant imbalance between groups.",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods. ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death) (NEJM 2010;362:1575-85 Supplementary Appendix 1).","PN","Additional visits can be scheduled as needed to monitor and assure appropriate implementation of the study interventions. For the purpose of event ascertainment, all participants in all treatment groups will be queried regarding the occurrence of a possible event on the same schedule, specifically every 4 months.","PN","Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently.","NA",null,"NA",null,"Low","Low","ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death). Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently.",null,null,"PY","the final version of the protocol was approved on January 05, 2009, previous to the journal publication (NEJM 2010;362:1575-85, Supplementary Appendix 2).","PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)","PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)","Low","Low","Individual-patient data available.",null,null,"Some concerns","Some concerns","There is some concerns in one domain."]
["2021/09/17 11.54",2,"JE","ACCORD","ACCORD 2010","Low targets","Standard targets","total serious adverse events","RR=0.98","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","PY","Y","An internet-based, web browser randomization procedure was employed","N","Described in Table 1 of the main article","Low","Low","An internet-based, web browser randomization procedure was employed.",null,null,"Y","Y","This is an unmasked open trial","NI",null,"NA",null,"NA",null,"Y","Analyses of primary and secondary outcomes were performed with the use of time-to-event methods according to the intention-to-treat principle (Methods section, N Engl J Med 2010;362:1575-85).","NA",null,"Some concerns","Some concerns","This is an unmasked open trial",null,null,"Y","patients lost to follow-up in study groups were 29/2362 vs  29/2371 (NEJM 2010;362:1575-85).","NA",null,"NA",null,"NA","Some concerns","Low","Low","No signifficant imbalance between groups",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods. ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death) (NEJM 2010;362:1575-85 Supplementary Appendix 1).","PN","Additional visits can be scheduled as needed to monitor and assure appropriate implementation of the study interventions. For the purpose of event ascertainment, all participants in all treatment groups will be queried regarding the occurrence of a possible event on the same schedule, specifically every 4 months.","PN","Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently.","NA",null,"NA","Some concerns","Low","Low","ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death). Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently.",null,null,"PY","the final version of the protocol was approved on January 05, 2009, previous to the journal publication (NEJM 2010;362:1575-85, Supplementary Appendix 2).","PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)","PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","there is some concerns in one domain"]
["2021/09/17 11.54",3,"JE","ACCORD","ACCORD 2010","Low targets","Standard targets","total cardiovascular events","RR=0.92","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","PY","Y","An internet-based, web browser randomization procedure was employed","N","Described in Table 1 of the main article","Low","Low","An internet-based, web browser randomization procedure was employed.",null,null,"Y","Y","This is an unmasked open trial","NI",null,"NA",null,"NA",null,"Y","Analyses of primary and secondary outcomes were performed with the use of time-to-event methods according to the intention-to-treat principle (Methods section, N Engl J Med 2010;362:1575-85).","NA",null,"Some concerns","Some concerns","This is an unmasked open trial",null,null,"Y","patients lost to follow-up in study groups were 29/2362 vs  29/2371 (NEJM 2010;362:1575-85).","NA",null,"NA",null,"NA","Consort diagram. Section 2","Low","Low","No signifficant imbalance between groups",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods. ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death) (NEJM 2010;362:1575-85 Supplementary Appendix 1).","PN","Additional visits can be scheduled as needed to monitor and assure appropriate implementation of the study interventions. For the purpose of event ascertainment, all participants in all treatment groups will be queried regarding the occurrence of a possible event on the same schedule, specifically every 4 months.","PN","Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently.","NA",null,"NA","Additional visits can be scheduled as needed to monitor and assure appropriate implementation of the study interventions. For the purpose of event ascertainment, all participants in all treatment groups will be queried regarding the occurrence of a possible event on the same schedule, specifically every 4 months.","Low","Low","ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death). Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently.",null,null,"PY","the final version of the protocol was approved on January 05, 2009, previous to the journal publication (NEJM 2010;362:1575-85, Supplementary Appendix 2).","PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)","PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","there is some concerns in one domain"]
["2021/09/17 11.54",4,"JE","ACCORD","ACCORD 2010","Low targets","Standard targets","cardiovascular mortality","RR=1.16","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","PY","Y","An internet-based, web browser randomization procedure was employed","N","Described in Table 1 of the main article","Low","Low","An internet-based, web browser randomization procedure was employed.",null,null,"Y","Y","This is an unmasked open trial","NI",null,"NA",null,"NA",null,"Y","Analyses of primary and secondary outcomes were performed with the use of time-to-event methods according to the intention-to-treat principle (Methods section, N Engl J Med 2010;362:1575-85).","NA",null,"Some concerns","Some concerns","This is an unmasked open trial",null,null,"Y","patients lost to follow-up in study groups were 29/2362 vs  29/2371 (NEJM 2010;362:1575-85).","NA",null,"NA",null,"NA",null,"Low","Low","No signifficant imbalance between groups",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods. ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death) (NEJM 2010;362:1575-85 Supplementary Appendix 1).","PN","Additional visits can be scheduled as needed to monitor and assure appropriate implementation of the study interventions. For the purpose of event ascertainment, all participants in all treatment groups will be queried regarding the occurrence of a possible event on the same schedule, specifically every 4 months.","PN","Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently.","NA",null,"NA","ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death). Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently.","Low","Low","ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death). Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently.",null,null,"PY","the final version of the protocol was approved on January 05, 2009, previous to the journal publication (NEJM 2010;362:1575-85, Supplementary Appendix 2).","PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)","PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","there is some concerns in one domain"]
["2021/09/17 11.54",5,"JE","ACCORD","ACCORD 2010","Low targets","Standard targets","kidney failure","RR=0.51","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","PY","Y","An internet-based, web browser randomization procedure was employed","N","Described in Table 1 of the main article","Low","Low","An internet-based, web browser randomization procedure was employed.",null,null,"Y","Y","This is an unmasked open trial","NI",null,"NA",null,"NA",null,"Y","Analyses of primary and secondary outcomes were performed with the use of time-to-event methods according to the intention-to-treat principle (Methods section, N Engl J Med 2010;362:1575-85).","NA",null,"Some concerns","Some concerns","This is an unmasked open trial",null,null,"Y","patients lost to follow-up in study groups were 29/2362 vs  29/2371 (NEJM 2010;362:1575-85).","NA",null,"NA",null,"NA",null,"Low","Low","No signifficant imbalance between groups",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods. ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death) (NEJM 2010;362:1575-85 Supplementary Appendix 1).","PN","Additional visits can be scheduled as needed to monitor and assure appropriate implementation of the study interventions. For the purpose of event ascertainment, all participants in all treatment groups will be queried regarding the occurrence of a possible event on the same schedule, specifically every 4 months.","PN","Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently.","NA",null,"NA",null,"Low","Low","ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death). Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently.",null,null,"PY","the final version of the protocol was approved on January 05, 2009, previous to the journal publication (NEJM 2010;362:1575-85, Supplementary Appendix 2).","PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)","PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","there is some concerns in one domain"]
["2021/09/17 11.54",6,"JE","ACCORD","ACCORD 2010","Low targets","Standard targets","Participant withdrawals due to adverse effects"]
["2021/09/17 11.55",7,"JE","ACCORD","ACCORD 2010","Low targets","Standard targets","Systolic blood pressure difference from baseline at one year","MD=12.90","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","PY","Y","An internet-based, web browser randomization procedure was employed","N","Described in Table 1 of the main article","Low","Low","An internet-based, web browser randomization procedure was employed.",null,null,"Y","Y","This is an unmasked open trial","NI",null,"NA",null,"NA",null,"Y","Analyses of primary and secondary outcomes were performed with the use of time-to-event methods according to the intention-to-treat principle (Methods section, N Engl J Med 2010;362:1575-85).","NA",null,"Some concerns","Some concerns","This is an unmasked open trial",null,null,"Y","patients lost to follow-up in study groups were 29/2362 vs  29/2371 (NEJM 2010;362:1575-85).","NA",null,"NA",null,"NA",null,"Low","Low","No signifficant imbalance between groups",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods. ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death) (NEJM 2010;362:1575-85 Supplementary Appendix 1).","PN","Additional visits can be scheduled as needed to monitor and assure appropriate implementation of the study interventions. For the purpose of event ascertainment, all participants in all treatment groups will be queried regarding the occurrence of a possible event on the same schedule, specifically every 4 months.","PN","Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently.","NA",null,"NA",null,"Low","Low","ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death). Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently.",null,null,"PY","the final version of the protocol was approved on January 05, 2009, previous to the journal publication (NEJM 2010;362:1575-85, Supplementary Appendix 2).","PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)","PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","there is some concerns in one domain"]
["2021/09/17 11.56",8,"JE","ACCORD","ACCORD 2010","Low targets","Standard targets","Diastolic blood pressure difference from baseline at one year","MD=5.50","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","PY","Y","An internet-based, web browser randomization procedure was employed","N","Described in Table 1 of the main article","Low","Low","An internet-based, web browser randomization procedure was employed.",null,null,"Y","Y","This is an unmasked open trial","NI",null,"NA",null,"NA",null,"Y","Analyses of primary and secondary outcomes were performed with the use of time-to-event methods according to the intention-to-treat principle (Methods section, N Engl J Med 2010;362:1575-85).","NA",null,"Some concerns","Some concerns","This is an unmasked open trial",null,null,"Y","patients lost to follow-up in study groups were 29/2362 vs  29/2371 (NEJM 2010;362:1575-85).","NA",null,"NA",null,"NA",null,"Low","Low","No signifficant imbalance between groups",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods. ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death) (NEJM 2010;362:1575-85 Supplementary Appendix 1).","PN","Additional visits can be scheduled as needed to monitor and assure appropriate implementation of the study interventions. For the purpose of event ascertainment, all participants in all treatment groups will be queried regarding the occurrence of a possible event on the same schedule, specifically every 4 months.","PN","Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently.","NA",null,"NA",null,"Low","Low","ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death). Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently.",null,null,"PY","the final version of the protocol was approved on January 05, 2009, previous to the journal publication (NEJM 2010;362:1575-85, Supplementary Appendix 2).","PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)","PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","there is some concerns in one domain"]
["2021/09/17 11.57",9,"JE","ACCORD","ACCORD 2010","Low targets","Standard targets","Doubling of serum creatinine level or 50% reduction in GFR at the end of study","RR=1.69","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","PY","Y","An internet-based, web browser randomization procedure was employed","N","Described in Table 1 of the main article","Low","Low","An internet-based, web browser randomization procedure was employed.",null,null,"Y","Y","This is an unmasked open trial","NI",null,"NA",null,"NA",null,"Y","Analyses of primary and secondary outcomes were performed with the use of time-to-event methods according to the intention-to-treat principle (Methods section, N Engl J Med 2010;362:1575-85).","NA",null,"Some concerns","Some concerns","This is an unmasked open trial",null,null,"Y","patients lost to follow-up in study groups were 29/2362 vs  29/2371 (NEJM 2010;362:1575-85).","NA",null,"NA",null,"NA",null,"Low","Low","No signifficant imbalance between groups",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods. ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death) (NEJM 2010;362:1575-85 Supplementary Appendix 1).","PN","Additional visits can be scheduled as needed to monitor and assure appropriate implementation of the study interventions. For the purpose of event ascertainment, all participants in all treatment groups will be queried regarding the occurrence of a possible event on the same schedule, specifically every 4 months.","PN","Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently.","NA",null,"NA",null,"Low","Low","ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death). Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently.",null,null,"PY","the final version of the protocol was approved on January 05, 2009, previous to the journal publication (NEJM 2010;362:1575-85, Supplementary Appendix 2).","PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)","PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","there is some concerns in one domain"]
["2021/09/17 11.58",10,"JE","ACCORD","ACCORD 2010","Low targets","Standard targets","Proportion of participants reaching target levels of blood pressure at the end of study","RR=0.74","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","PY","Y","An internet-based, web browser randomization procedure was employed","N","Described in Table 1 of the main article","Low","Low","An internet-based, web browser randomization procedure was employed.",null,null,"Y","Y","This is an unmasked open trial","NI",null,"NA",null,"NA",null,"Y","Analyses of primary and secondary outcomes were performed with the use of time-to-event methods according to the intention-to-treat principle (Methods section, N Engl J Med 2010;362:1575-85).","NA",null,"Some concerns","Some concerns","This is an unmasked open trial",null,null,"Y","patients lost to follow-up in study groups were 29/2362 vs  29/2371 (NEJM 2010;362:1575-85).","NA",null,"NA",null,"NA",null,"Low","Low","No signifficant imbalance between groups",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods. ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death) (NEJM 2010;362:1575-85 Supplementary Appendix 1).","PN","Additional visits can be scheduled as needed to monitor and assure appropriate implementation of the study interventions. For the purpose of event ascertainment, all participants in all treatment groups will be queried regarding the occurrence of a possible event on the same schedule, specifically every 4 months.","PN","Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently.","NA",null,"NA",null,"Low","Low","ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death). Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently.",null,null,"PY","the final version of the protocol was approved on January 05, 2009, previous to the journal publication (NEJM 2010;362:1575-85, Supplementary Appendix 2).","PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)","PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","there is some concerns in one domain"]
["2021/09/17 11.59",11,"JE","ACCORD","ACCORD 2010","Low targets","Standard targets","Number of antihypertensive drugs that each participant needed at the end of study","MD=1.30","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","PY","Y","An internet-based, web browser randomization procedure was employed","N","Described in Table 1 of the main article","Low","Low","An internet-based, web browser randomization procedure was employed.",null,null,"Y","Y","This is an unmasked open trial","NI",null,"NA",null,"NA",null,"Y","Analyses of primary and secondary outcomes were performed with the use of time-to-event methods according to the intention-to-treat principle (Methods section, N Engl J Med 2010;362:1575-85).","NA",null,"Some concerns","Some concerns","This is an unmasked open trial",null,null,"Y","patients lost to follow-up in study groups were 29/2362 vs  29/2371 (NEJM 2010;362:1575-85).","NA",null,"NA",null,"NA",null,"Low","Low","No signifficant imbalance between groups",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods. ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death) (NEJM 2010;362:1575-85 Supplementary Appendix 1).","PN","Additional visits can be scheduled as needed to monitor and assure appropriate implementation of the study interventions. For the purpose of event ascertainment, all participants in all treatment groups will be queried regarding the occurrence of a possible event on the same schedule, specifically every 4 months.","PN","Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently.","NA",null,"NA",null,"Low","Low","ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death). Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently.",null,null,"PY","the final version of the protocol was approved on January 05, 2009, previous to the journal publication (NEJM 2010;362:1575-85, Supplementary Appendix 2).","PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)","PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","there is some concerns in one domain"]
["2021/09/17 12.05",12,"JE","HOT","HOT 1998","Low targets","Standard targets","total mortality","RR=1.10","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Regulatory document (e.g. Clinical Study Report, Drug Approval Package)","PY","Y","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975).","N","There doesn't seem to be a significant imbalance in follow-up diagram","Low","Low","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975).",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","The study was analysed according to the intention to treat principle (CSR, HOT trial).","NA",null,"Some concerns","Some concerns","open trial",null,null,"Y","patients lost to follow-up in study groups were 169/6264 (<90 mmHg) vs 157/6264 (<85 mmHg) vs 165/6262 (80 mmHg) (Lancet 1998; 351: 1755–62).","NI",null,"NI",null,"PN",null,"Low","Low","No significant differences among targets have been detected. ",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (CSR, section Efficacy and Safety Measurements and Variables, page 22). Seated systolic and diastolic blood pressure and heart rate were measured after 5 minutes’ rest. Three measurements were to be made, separated by at least a 15-second interval. All study decisions were based on the mean of the three diastolic blood pressures.\nBlood pressure was to be measured in the same arm at each visit using an automatic blood pressure measuring device (Visomat OZ, D2, International, Hestia, Germany) and a cuff of appropriate size relative to the patients’ arm. The cuff had to be at heart level and the arm supported at the time of the measurement.\nThe Visomat OZ (D2 International) blood pressure measuring device was compared to standard blood pressure measuring equipment in a separate study (see Appendix\n16.1.10 for publication). Heart rate was also measured by the automatic blood pressure device.\nIdeally, visits were to take place at the same time of the day and measurements performed at the end of the dosing interval and by the same person.\nThe diastolic blood pressure achieved during active antihypertensive therapy in the study was calculated as the mean of the diastolic blood pressures recorded at the\n6-month Follow-up Visit and at all subsequent follow-up visits. In patients who had suffered non-fatal myocardial infarction, only measurements made prior to the\nevent were used to calculate the achieved diastolic blood pressure.\nThe evaluation of clinical events was performed by an Independent Clinical Event Committee who was blinded regarding the target blood pressure to which the\npatients were randomised as well as their randomisation to either ASA or placebo. Clinical events were evaluated using all available information, such as hospital\nrecords, physician’s records, police reports, death certificates and post-mortem reports. This information had to be sent to the Coordinating Centre where it was\nblinded and forwarded to the Independent Clinical Event Committee. If no other information was available, the Independent Clinical Event Committee based the\nclassification on a report from the responsible investigator.\n","PN","The first follow·up visit is scheduled 3 months after the Randomisation Visit. The next follow-up visit will take place 6 months after the Randomisation Visit and thereafter visits will take place every 6 months. Current antihypertensive medication as well as seated blood pressure and heart rate are recorded. Clinical events and side effects occurring since previous visit are recorded . It is up to the investigator to judge if visits are needed more frequently. However, no data will be collected at such extra visits.","PN","The study is a prospective, randomised, open trial with blinded clinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality.","NA",null,"NA",null,"Low","Low","The study is a prospective, randomised, open trial with blinded clinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality.",null,null,"PY","the final version of the protocol was approved in 1994, previous to the journal publication (1998) (L. Hansson & A. Zanchetti. The Hypertension Optimal Treatment (HOT) Study—Patient Characteristics: Randomization, Risk Profiles, and Early Blood Pressure Results. Blood Pressure Volume 3, 1994 - Issue 5).","N","The database shows all required results","N","The database shows all required results","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","there were some concerns in two domains"]
["2021/09/17 12.06",13,"JE","HOT","HOT 1998","Low targets","Standard targets","total serious adverse events","RR=1.13","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Regulatory document (e.g. Clinical Study Report, Drug Approval Package)","PY","Y","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975).","N","There doesn't seem to be a significant imbalance in follow-up diagram","Low","Low","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975).",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","The study was analysed according to the intention to treat principle (CSR, HOT trial).","NA",null,"Some concerns","Some concerns","open trial",null,null,"Y","patients lost to follow-up in study groups were 169/6264 (<90 mmHg) vs 157/6264 (<85 mmHg) vs 165/6262 (80 mmHg) (Lancet 1998; 351: 1755–62).","NI",null,"NI",null,"PN",null,"Low","Low","No significant differences among targets have been detected. ",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (CSR, section Efficacy and Safety Measurements and Variables, page 22). Seated systolic and diastolic blood pressure and heart rate were measured after 5 minutes’ rest. Three measurements were to be made, separated by at least a 15-second interval. All study decisions were based on the mean of the three diastolic blood pressures.\nBlood pressure was to be measured in the same arm at each visit using an automatic blood pressure measuring device (Visomat OZ, D2, International, Hestia, Germany) and a cuff of appropriate size relative to the patients’ arm. The cuff had to be at heart level and the arm supported at the time of the measurement.\nThe Visomat OZ (D2 International) blood pressure measuring device was compared to standard blood pressure measuring equipment in a separate study (see Appendix\n16.1.10 for publication). Heart rate was also measured by the automatic blood pressure device.\nIdeally, visits were to take place at the same time of the day and measurements performed at the end of the dosing interval and by the same person.\nThe diastolic blood pressure achieved during active antihypertensive therapy in the study was calculated as the mean of the diastolic blood pressures recorded at the\n6-month Follow-up Visit and at all subsequent follow-up visits. In patients who had suffered non-fatal myocardial infarction, only measurements made prior to the\nevent were used to calculate the achieved diastolic blood pressure.\nThe evaluation of clinical events was performed by an Independent Clinical Event Committee who was blinded regarding the target blood pressure to which the\npatients were randomised as well as their randomisation to either ASA or placebo. Clinical events were evaluated using all available information, such as hospital\nrecords, physician’s records, police reports, death certificates and post-mortem reports. This information had to be sent to the Coordinating Centre where it was\nblinded and forwarded to the Independent Clinical Event Committee. If no other information was available, the Independent Clinical Event Committee based the\nclassification on a report from the responsible investigator.\n","PN","The first follow·up visit is scheduled 3 months after the Randomi·\nsation Visit. The next follow-up visit will take place 6 months after the Randomisation Visit and thereafter visits will take place every 6 months. Current antihypertensive medication as well as seated blood pressure and heart rate are recorded. Clinical events and side effects occurring since previous visit are recorded . It is up to the investigator to judge if visits are needed more frequently. However, no data will be collected at such extra visits.","PN","The study is a prospective, randomised, open trial with blinded\nclinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality.","NA",null,"NA",null,"Low","Low","The study is a prospective, randomised, open trial with blinded clinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality.",null,null,"PY","the final version of the protocol was approved in 1994, previous to the journal publication (1998) (L. Hansson & A. Zanchetti. The Hypertension Optimal Treatment (HOT) Study—Patient Characteristics: Randomization, Risk Profiles, and Early Blood Pressure Results. Blood Pressure Volume 3, 1994 - Issue 5).","N","The database shows all required results","N","The database shows all required results","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","there were some concerns in two domains"]
["2021/09/17 12.07",14,"JE","HOT","HOT 1998","Low targets","Standard targets","total cardiovascular events","RR=1.15","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Regulatory document (e.g. Clinical Study Report, Drug Approval Package)","PY","Y","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975).","N","There doesn't seem to be a significant imbalance in follow-up diagram","Low","Low","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975).",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","The study was analysed according to the intention to treat principle (CSR, HOT trial).","NA",null,"Some concerns","Some concerns","open trial",null,null,"Y","patients lost to follow-up in study groups were 169/6264 (<90 mmHg) vs 157/6264 (<85 mmHg) vs 165/6262 (80 mmHg) (Lancet 1998; 351: 1755–62).","NI",null,"NI",null,"PN",null,"Low","Low","No significant differences among targets have been detected. ",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (CSR, section Efficacy and Safety Measurements and Variables, page 22). Seated systolic and diastolic blood pressure and heart rate were measured after 5 minutes’ rest. Three measurements were to be made, separated by at least a 15-second interval. All study decisions were based on the mean of the three diastolic blood pressures.\nBlood pressure was to be measured in the same arm at each visit using an automatic blood pressure measuring device (Visomat OZ, D2, International, Hestia, Germany) and a cuff of appropriate size relative to the patients’ arm. The cuff had to be at heart level and the arm supported at the time of the measurement.\nThe Visomat OZ (D2 International) blood pressure measuring device was compared to standard blood pressure measuring equipment in a separate study (see Appendix\n16.1.10 for publication). Heart rate was also measured by the automatic blood pressure device.\nIdeally, visits were to take place at the same time of the day and measurements performed at the end of the dosing interval and by the same person.\nThe diastolic blood pressure achieved during active antihypertensive therapy in the study was calculated as the mean of the diastolic blood pressures recorded at the\n6-month Follow-up Visit and at all subsequent follow-up visits. In patients who had suffered non-fatal myocardial infarction, only measurements made prior to the\nevent were used to calculate the achieved diastolic blood pressure.\nThe evaluation of clinical events was performed by an Independent Clinical Event Committee who was blinded regarding the target blood pressure to which the\npatients were randomised as well as their randomisation to either ASA or placebo. Clinical events were evaluated using all available information, such as hospital\nrecords, physician’s records, police reports, death certificates and post-mortem reports. This information had to be sent to the Coordinating Centre where it was\nblinded and forwarded to the Independent Clinical Event Committee. If no other information was available, the Independent Clinical Event Committee based the\nclassification on a report from the responsible investigator.\n","PN","The first follow·up visit is scheduled 3 months after the Randomi·\nsation Visit. The next follow-up visit will take place 6 months after the Randomisation Visit and thereafter visits will take place every 6 months. Current antihypertensive medication as well as seated blood pressure and heart rate are recorded. Clinical events and side effects occurring since previous visit are recorded . It is up to the investigator to judge if visits are needed more frequently. However, no data will be collected at such extra visits.","PN","The study is a prospective, randomised, open trial with blinded\nclinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality.","NA",null,"NA",null,"Low","Low","The study is a prospective, randomised, open trial with blinded clinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality.",null,null,"PY","the final version of the protocol was approved in 1994, previous to the journal publication (1998) (L. Hansson & A. Zanchetti. The Hypertension Optimal Treatment (HOT) Study—Patient Characteristics: Randomization, Risk Profiles, and Early Blood Pressure Results. Blood Pressure Volume 3, 1994 - Issue 5).","N","The database shows all required results","N","The database shows all required results","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","there were some concerns in two domains"]
["2021/09/17 12.08",15,"JE","HOT","HOT 1998","Low targets","Standard targets","cardiovascular mortality","RR=1.06","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Regulatory document (e.g. Clinical Study Report, Drug Approval Package)","PY","Y","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975).","N","There doesn't seem to be a significant imbalance in follow-up diagram","Low","Low","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975).",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","The study was analysed according to the intention to treat principle (CSR, HOT trial).","NA",null,"Some concerns","Some concerns","open trial",null,null,"Y","patients lost to follow-up in study groups were 169/6264 (<90 mmHg) vs 157/6264 (<85 mmHg) vs 165/6262 (80 mmHg) (Lancet 1998; 351: 1755–62).","NI",null,"NI",null,"PN",null,"Low","Low","No significant differences among targets have been detected. ",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (CSR, section Efficacy and Safety Measurements and Variables, page 22). Seated systolic and diastolic blood pressure and heart rate were measured after 5 minutes’ rest. Three measurements were to be made, separated by at least a 15-second interval. All study decisions were based on the mean of the three diastolic blood pressures.\nBlood pressure was to be measured in the same arm at each visit using an automatic blood pressure measuring device (Visomat OZ, D2, International, Hestia, Germany) and a cuff of appropriate size relative to the patients’ arm. The cuff had to be at heart level and the arm supported at the time of the measurement.\nThe Visomat OZ (D2 International) blood pressure measuring device was compared to standard blood pressure measuring equipment in a separate study (see Appendix\n16.1.10 for publication). Heart rate was also measured by the automatic blood pressure device.\nIdeally, visits were to take place at the same time of the day and measurements performed at the end of the dosing interval and by the same person.\nThe diastolic blood pressure achieved during active antihypertensive therapy in the study was calculated as the mean of the diastolic blood pressures recorded at the\n6-month Follow-up Visit and at all subsequent follow-up visits. In patients who had suffered non-fatal myocardial infarction, only measurements made prior to the\nevent were used to calculate the achieved diastolic blood pressure.\nThe evaluation of clinical events was performed by an Independent Clinical Event Committee who was blinded regarding the target blood pressure to which the\npatients were randomised as well as their randomisation to either ASA or placebo. Clinical events were evaluated using all available information, such as hospital\nrecords, physician’s records, police reports, death certificates and post-mortem reports. This information had to be sent to the Coordinating Centre where it was\nblinded and forwarded to the Independent Clinical Event Committee. If no other information was available, the Independent Clinical Event Committee based the\nclassification on a report from the responsible investigator.\n","PN","The first follow·up visit is scheduled 3 months after the Randomi·\nsation Visit. The next follow-up visit will take place 6 months after the Randomisation Visit and thereafter visits will take place every 6 months. Current antihypertensive medication as well as seated blood pressure and heart rate are recorded. Clinical events and side effects occurring since previous visit are recorded . It is up to the investigator to judge if visits are needed more frequently. However, no data will be collected at such extra visits.","PN","The study is a prospective, randomised, open trial with blinded\nclinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality.","NA",null,"NA",null,"Low","Low","The study is a prospective, randomised, open trial with blinded clinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality.",null,null,"PY","the final version of the protocol was approved in 1994, previous to the journal publication (1998) (L. Hansson & A. Zanchetti. The Hypertension Optimal Treatment (HOT) Study—Patient Characteristics: Randomization, Risk Profiles, and Early Blood Pressure Results. Blood Pressure Volume 3, 1994 - Issue 5).","N","The database shows all required results","N","The database shows all required results","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","there were some concerns in two domains"]
["2021/09/17 12.09",16,"JE","HOT","HOT 1998","Low targets","Standard targets","kidney failure",null,null,null,null,null,null,null,null,null,null,null,null,"The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975).",null,null,"-",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"individual-patient data available"]
["2021/09/17 12.10",17,"JE","HOT","HOT 1998","Low targets","Standard targets","Participant withdrawals due to adverse effects","RR=0.98","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Regulatory document (e.g. Clinical Study Report, Drug Approval Package)","PY","Y","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975).","N","There doesn't seem to be a significant imbalance in follow-up diagram","Low","Low","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975).",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","The study was analysed according to the intention to treat principle (CSR, HOT trial).","NA",null,"Some concerns","Some concerns","open trial",null,null,"Y","patients lost to follow-up in study groups were 169/6264 (<90 mmHg) vs 157/6264 (<85 mmHg) vs 165/6262 (80 mmHg) (Lancet 1998; 351: 1755–62).","NI",null,"NI",null,"PN",null,"Low","Low","No significant differences among targets have been detected. ",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (CSR, section Efficacy and Safety Measurements and Variables, page 22). Seated systolic and diastolic blood pressure and heart rate were measured after 5 minutes’ rest. Three measurements were to be made, separated by at least a 15-second interval. All study decisions were based on the mean of the three diastolic blood pressures.\nBlood pressure was to be measured in the same arm at each visit using an automatic blood pressure measuring device (Visomat OZ, D2, International, Hestia, Germany) and a cuff of appropriate size relative to the patients’ arm. The cuff had to be at heart level and the arm supported at the time of the measurement.\nThe Visomat OZ (D2 International) blood pressure measuring device was compared to standard blood pressure measuring equipment in a separate study (see Appendix\n16.1.10 for publication). Heart rate was also measured by the automatic blood pressure device.\nIdeally, visits were to take place at the same time of the day and measurements performed at the end of the dosing interval and by the same person.\nThe diastolic blood pressure achieved during active antihypertensive therapy in the study was calculated as the mean of the diastolic blood pressures recorded at the\n6-month Follow-up Visit and at all subsequent follow-up visits. In patients who had suffered non-fatal myocardial infarction, only measurements made prior to the\nevent were used to calculate the achieved diastolic blood pressure.\nThe evaluation of clinical events was performed by an Independent Clinical Event Committee who was blinded regarding the target blood pressure to which the\npatients were randomised as well as their randomisation to either ASA or placebo. Clinical events were evaluated using all available information, such as hospital\nrecords, physician’s records, police reports, death certificates and post-mortem reports. This information had to be sent to the Coordinating Centre where it was\nblinded and forwarded to the Independent Clinical Event Committee. If no other information was available, the Independent Clinical Event Committee based the\nclassification on a report from the responsible investigator.\n","PN","The first follow·up visit is scheduled 3 months after the Randomi·\nsation Visit. The next follow-up visit will take place 6 months after the Randomisation Visit and thereafter visits will take place every 6 months. Current antihypertensive medication as well as seated blood pressure and heart rate are recorded. Clinical events and side effects occurring since previous visit are recorded . It is up to the investigator to judge if visits are needed more frequently. However, no data will be collected at such extra visits.","PN","The study is a prospective, randomised, open trial with blinded\nclinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality.","NA",null,"NA",null,"Low","Low","The study is a prospective, randomised, open trial with blinded clinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality.",null,null,"PY","the final version of the protocol was approved in 1994, previous to the journal publication (1998) (L. Hansson & A. Zanchetti. The Hypertension Optimal Treatment (HOT) Study—Patient Characteristics: Randomization, Risk Profiles, and Early Blood Pressure Results. Blood Pressure Volume 3, 1994 - Issue 5).","N","The database shows all required results","N","The database shows all required results","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","there were some concerns in two domains"]
["2021/09/17 12.11",18,"JE","HOT","HOT 1998","Low targets","Standard targets","Systolic blood pressure difference from baseline at one year","MD=3.40","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Regulatory document (e.g. Clinical Study Report, Drug Approval Package)","PY","Y","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975).","N","There doesn't seem to be a significant imbalance in follow-up diagram","Low","Low","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975).",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","The study was analysed according to the intention to treat principle (CSR, HOT trial).","NA",null,"Some concerns","Some concerns","open trial",null,null,"Y","patients lost to follow-up in study groups were 169/6264 (<90 mmHg) vs 157/6264 (<85 mmHg) vs 165/6262 (80 mmHg) (Lancet 1998; 351: 1755–62).","NI",null,"NI",null,"PN",null,"Low","Low","No significant differences among targets have been detected. ",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (CSR, section Efficacy and Safety Measurements and Variables, page 22). Seated systolic and diastolic blood pressure and heart rate were measured after 5 minutes’ rest. Three measurements were to be made, separated by at least a 15-second interval. All study decisions were based on the mean of the three diastolic blood pressures.\nBlood pressure was to be measured in the same arm at each visit using an automatic blood pressure measuring device (Visomat OZ, D2, International, Hestia, Germany) and a cuff of appropriate size relative to the patients’ arm. The cuff had to be at heart level and the arm supported at the time of the measurement.\nThe Visomat OZ (D2 International) blood pressure measuring device was compared to standard blood pressure measuring equipment in a separate study (see Appendix\n16.1.10 for publication). Heart rate was also measured by the automatic blood pressure device.\nIdeally, visits were to take place at the same time of the day and measurements performed at the end of the dosing interval and by the same person.\nThe diastolic blood pressure achieved during active antihypertensive therapy in the study was calculated as the mean of the diastolic blood pressures recorded at the\n6-month Follow-up Visit and at all subsequent follow-up visits. In patients who had suffered non-fatal myocardial infarction, only measurements made prior to the\nevent were used to calculate the achieved diastolic blood pressure.\nThe evaluation of clinical events was performed by an Independent Clinical Event Committee who was blinded regarding the target blood pressure to which the\npatients were randomised as well as their randomisation to either ASA or placebo. Clinical events were evaluated using all available information, such as hospital\nrecords, physician’s records, police reports, death certificates and post-mortem reports. This information had to be sent to the Coordinating Centre where it was\nblinded and forwarded to the Independent Clinical Event Committee. If no other information was available, the Independent Clinical Event Committee based the\nclassification on a report from the responsible investigator.\n","PN","The first follow·up visit is scheduled 3 months after the Randomi·\nsation Visit. The next follow-up visit will take place 6 months after the Randomisation Visit and thereafter visits will take place every 6 months. Current antihypertensive medication as well as seated blood pressure and heart rate are recorded. Clinical events and side effects occurring since previous visit are recorded . It is up to the investigator to judge if visits are needed more frequently. However, no data will be collected at such extra visits.","PN","The study is a prospective, randomised, open trial with blinded\nclinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality.","NA",null,"NA",null,"Low","Low","The study is a prospective, randomised, open trial with blinded clinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality.",null,null,"PY","the final version of the protocol was approved in 1994, previous to the journal publication (1998) (L. Hansson & A. Zanchetti. The Hypertension Optimal Treatment (HOT) Study—Patient Characteristics: Randomization, Risk Profiles, and Early Blood Pressure Results. Blood Pressure Volume 3, 1994 - Issue 5).","N","The database shows all required results","N","The database shows all required results","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","there were some concerns in two domains"]
["2021/09/17 12.12",19,"JE","HOT","HOT 1998","Low targets","Standard targets","Diastolic blood pressure difference from baseline at one year","MD=3.40","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Regulatory document (e.g. Clinical Study Report, Drug Approval Package)","PY","Y","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975).","N","There doesn't seem to be a significant imbalance in follow-up diagram","Low","Low","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975).",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","The study was analysed according to the intention to treat principle (CSR, HOT trial).","NA",null,"Some concerns","Some concerns","open trial",null,null,"Y","patients lost to follow-up in study groups were 169/6264 (<90 mmHg) vs 157/6264 (<85 mmHg) vs 165/6262 (80 mmHg) (Lancet 1998; 351: 1755–62).","NI",null,"NI",null,"PN",null,"Low","Low","No significant differences among targets have been detected. ",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (CSR, section Efficacy and Safety Measurements and Variables, page 22). Seated systolic and diastolic blood pressure and heart rate were measured after 5 minutes’ rest. Three measurements were to be made, separated by at least a 15-second interval. All study decisions were based on the mean of the three diastolic blood pressures.\nBlood pressure was to be measured in the same arm at each visit using an automatic blood pressure measuring device (Visomat OZ, D2, International, Hestia, Germany) and a cuff of appropriate size relative to the patients’ arm. The cuff had to be at heart level and the arm supported at the time of the measurement.\nThe Visomat OZ (D2 International) blood pressure measuring device was compared to standard blood pressure measuring equipment in a separate study (see Appendix\n16.1.10 for publication). Heart rate was also measured by the automatic blood pressure device.\nIdeally, visits were to take place at the same time of the day and measurements performed at the end of the dosing interval and by the same person.\nThe diastolic blood pressure achieved during active antihypertensive therapy in the study was calculated as the mean of the diastolic blood pressures recorded at the\n6-month Follow-up Visit and at all subsequent follow-up visits. In patients who had suffered non-fatal myocardial infarction, only measurements made prior to the\nevent were used to calculate the achieved diastolic blood pressure.\nThe evaluation of clinical events was performed by an Independent Clinical Event Committee who was blinded regarding the target blood pressure to which the\npatients were randomised as well as their randomisation to either ASA or placebo. Clinical events were evaluated using all available information, such as hospital\nrecords, physician’s records, police reports, death certificates and post-mortem reports. This information had to be sent to the Coordinating Centre where it was\nblinded and forwarded to the Independent Clinical Event Committee. If no other information was available, the Independent Clinical Event Committee based the\nclassification on a report from the responsible investigator.\n","PN","The first follow·up visit is scheduled 3 months after the Randomi·\nsation Visit. The next follow-up visit will take place 6 months after the Randomisation Visit and thereafter visits will take place every 6 months. Current antihypertensive medication as well as seated blood pressure and heart rate are recorded. Clinical events and side effects occurring since previous visit are recorded . It is up to the investigator to judge if visits are needed more frequently. However, no data will be collected at such extra visits.","PN","The study is a prospective, randomised, open trial with blinded\nclinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality.","NA",null,"NA",null,"Low","Low","The study is a prospective, randomised, open trial with blinded clinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality.",null,null,"PY","the final version of the protocol was approved in 1994, previous to the journal publication (1998) (L. Hansson & A. Zanchetti. The Hypertension Optimal Treatment (HOT) Study—Patient Characteristics: Randomization, Risk Profiles, and Early Blood Pressure Results. Blood Pressure Volume 3, 1994 - Issue 5).","N","The database shows all required results","N","The database shows all required results","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","there were some concerns in two domains"]
["2021/09/17 12.13",20,"JE","HOT","HOT 1998","Low targets","Standard targets","Doubling of serum creatinine level or 50% reduction in GFR at the end of study","RR=0.80","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Regulatory document (e.g. Clinical Study Report, Drug Approval Package)","PY","Y","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975).","N","There doesn't seem to be a significant imbalance in follow-up diagram","Low","Low","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975).",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","The study was analysed according to the intention to treat principle (CSR, HOT trial).","NA",null,"Some concerns","Some concerns","open trial",null,null,"Y","patients lost to follow-up in study groups were 169/6264 (<90 mmHg) vs 157/6264 (<85 mmHg) vs 165/6262 (80 mmHg) (Lancet 1998; 351: 1755–62).","NI",null,"NI",null,"PN",null,"Low","Low","No significant differences among targets have been detected. ",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (CSR, section Efficacy and Safety Measurements and Variables, page 22). Seated systolic and diastolic blood pressure and heart rate were measured after 5 minutes’ rest. Three measurements were to be made, separated by at least a 15-second interval. All study decisions were based on the mean of the three diastolic blood pressures.\nBlood pressure was to be measured in the same arm at each visit using an automatic blood pressure measuring device (Visomat OZ, D2, International, Hestia, Germany) and a cuff of appropriate size relative to the patients’ arm. The cuff had to be at heart level and the arm supported at the time of the measurement.\nThe Visomat OZ (D2 International) blood pressure measuring device was compared to standard blood pressure measuring equipment in a separate study (see Appendix\n16.1.10 for publication). Heart rate was also measured by the automatic blood pressure device.\nIdeally, visits were to take place at the same time of the day and measurements performed at the end of the dosing interval and by the same person.\nThe diastolic blood pressure achieved during active antihypertensive therapy in the study was calculated as the mean of the diastolic blood pressures recorded at the\n6-month Follow-up Visit and at all subsequent follow-up visits. In patients who had suffered non-fatal myocardial infarction, only measurements made prior to the\nevent were used to calculate the achieved diastolic blood pressure.\nThe evaluation of clinical events was performed by an Independent Clinical Event Committee who was blinded regarding the target blood pressure to which the\npatients were randomised as well as their randomisation to either ASA or placebo. Clinical events were evaluated using all available information, such as hospital\nrecords, physician’s records, police reports, death certificates and post-mortem reports. This information had to be sent to the Coordinating Centre where it was\nblinded and forwarded to the Independent Clinical Event Committee. If no other information was available, the Independent Clinical Event Committee based the\nclassification on a report from the responsible investigator.\n","PN","The first follow·up visit is scheduled 3 months after the Randomi·\nsation Visit. The next follow-up visit will take place 6 months after the Randomisation Visit and thereafter visits will take place every 6 months. Current antihypertensive medication as well as seated blood pressure and heart rate are recorded. Clinical events and side effects occurring since previous visit are recorded . It is up to the investigator to judge if visits are needed more frequently. However, no data will be collected at such extra visits.","PN","The study is a prospective, randomised, open trial with blinded\nclinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality.","NA",null,"NA",null,"Low","Low","The study is a prospective, randomised, open trial with blinded clinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality.",null,null,"PY","the final version of the protocol was approved in 1994, previous to the journal publication (1998) (L. Hansson & A. Zanchetti. The Hypertension Optimal Treatment (HOT) Study—Patient Characteristics: Randomization, Risk Profiles, and Early Blood Pressure Results. Blood Pressure Volume 3, 1994 - Issue 5).","N","The database shows all required results","N","The database shows all required results","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","there were some concerns in two domains"]
["2021/09/17 12.14",21,"JE","HOT","HOT 1998","Low targets","Standard targets","Proportion of participants reaching target levels of blood pressure at the end of study","RR=0.60","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Regulatory document (e.g. Clinical Study Report, Drug Approval Package)","PY","Y","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975).","N","There doesn't seem to be a significant imbalance in follow-up diagram","Low","Low","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975).",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","The study was analysed according to the intention to treat principle (CSR, HOT trial).","NA",null,"Some concerns","Some concerns","open trial",null,null,"Y","patients lost to follow-up in study groups were 169/6264 (<90 mmHg) vs 157/6264 (<85 mmHg) vs 165/6262 (80 mmHg) (Lancet 1998; 351: 1755–62).","NI",null,"NI",null,"PN",null,"Low","Low","No significant differences among targets have been detected. ",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (CSR, section Efficacy and Safety Measurements and Variables, page 22). Seated systolic and diastolic blood pressure and heart rate were measured after 5 minutes’ rest. Three measurements were to be made, separated by at least a 15-second interval. All study decisions were based on the mean of the three diastolic blood pressures.\nBlood pressure was to be measured in the same arm at each visit using an automatic blood pressure measuring device (Visomat OZ, D2, International, Hestia, Germany) and a cuff of appropriate size relative to the patients’ arm. The cuff had to be at heart level and the arm supported at the time of the measurement.\nThe Visomat OZ (D2 International) blood pressure measuring device was compared to standard blood pressure measuring equipment in a separate study (see Appendix\n16.1.10 for publication). Heart rate was also measured by the automatic blood pressure device.\nIdeally, visits were to take place at the same time of the day and measurements performed at the end of the dosing interval and by the same person.\nThe diastolic blood pressure achieved during active antihypertensive therapy in the study was calculated as the mean of the diastolic blood pressures recorded at the\n6-month Follow-up Visit and at all subsequent follow-up visits. In patients who had suffered non-fatal myocardial infarction, only measurements made prior to the\nevent were used to calculate the achieved diastolic blood pressure.\nThe evaluation of clinical events was performed by an Independent Clinical Event Committee who was blinded regarding the target blood pressure to which the\npatients were randomised as well as their randomisation to either ASA or placebo. Clinical events were evaluated using all available information, such as hospital\nrecords, physician’s records, police reports, death certificates and post-mortem reports. This information had to be sent to the Coordinating Centre where it was\nblinded and forwarded to the Independent Clinical Event Committee. If no other information was available, the Independent Clinical Event Committee based the\nclassification on a report from the responsible investigator.\n","PN","The first follow·up visit is scheduled 3 months after the Randomi·\nsation Visit. The next follow-up visit will take place 6 months after the Randomisation Visit and thereafter visits will take place every 6 months. Current antihypertensive medication as well as seated blood pressure and heart rate are recorded. Clinical events and side effects occurring since previous visit are recorded . It is up to the investigator to judge if visits are needed more frequently. However, no data will be collected at such extra visits.","PN","The study is a prospective, randomised, open trial with blinded clinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality.","NA",null,"NA",null,"Low","Low","The study is a prospective, randomised, open trial with blinded clinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality.",null,null,"PY","the final version of the protocol was approved in 1994, previous to the journal publication (1998) (L. Hansson & A. Zanchetti. The Hypertension Optimal Treatment (HOT) Study—Patient Characteristics: Randomization, Risk Profiles, and Early Blood Pressure Results. Blood Pressure Volume 3, 1994 - Issue 5).","N","The database shows all required results","N","The database shows all required results","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","there were some concerns in two domains"]
["2021/09/17 12.15",22,"JE","HOT","HOT 1998","Low targets","Standard targets","Number of antihypertensive drugs that each participant needed at the end of study","MD=0.20","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol; Regulatory document (e.g. Clinical Study Report, Drug Approval Package)","PY","Y","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975).","N","There doesn't seem to be a significant imbalance in follow-up diagram","Low","Low","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975).",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","The study was analysed according to the intention to treat principle (CSR, HOT trial).","NA",null,"Some concerns","Some concerns","open trial",null,null,"Y","patients lost to follow-up in study groups were 169/6264 (<90 mmHg) vs 157/6264 (<85 mmHg) vs 165/6262 (80 mmHg) (Lancet 1998; 351: 1755–62).","NI",null,"NI",null,"PN",null,"Low","Low","No significant differences among targets have been detected. ",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (CSR, section Efficacy and Safety Measurements and Variables, page 22). Seated systolic and diastolic blood pressure and heart rate were measured after 5 minutes’ rest. Three measurements were to be made, separated by at least a 15-second interval. All study decisions were based on the mean of the three diastolic blood pressures.\nBlood pressure was to be measured in the same arm at each visit using an automatic blood pressure measuring device (Visomat OZ, D2, International, Hestia, Germany) and a cuff of appropriate size relative to the patients’ arm. The cuff had to be at heart level and the arm supported at the time of the measurement.\nThe Visomat OZ (D2 International) blood pressure measuring device was compared to standard blood pressure measuring equipment in a separate study (see Appendix\n16.1.10 for publication). Heart rate was also measured by the automatic blood pressure device.\nIdeally, visits were to take place at the same time of the day and measurements performed at the end of the dosing interval and by the same person.\nThe diastolic blood pressure achieved during active antihypertensive therapy in the study was calculated as the mean of the diastolic blood pressures recorded at the\n6-month Follow-up Visit and at all subsequent follow-up visits. In patients who had suffered non-fatal myocardial infarction, only measurements made prior to the\nevent were used to calculate the achieved diastolic blood pressure.\nThe evaluation of clinical events was performed by an Independent Clinical Event Committee who was blinded regarding the target blood pressure to which the\npatients were randomised as well as their randomisation to either ASA or placebo. Clinical events were evaluated using all available information, such as hospital\nrecords, physician’s records, police reports, death certificates and post-mortem reports. This information had to be sent to the Coordinating Centre where it was\nblinded and forwarded to the Independent Clinical Event Committee. If no other information was available, the Independent Clinical Event Committee based the\nclassification on a report from the responsible investigator.\n","PN","The first follow·up visit is scheduled 3 months after the Randomi·\nsation Visit. The next follow-up visit will take place 6 months after the Randomisation Visit and thereafter visits will take place every 6 months. Current antihypertensive medication as well as seated blood pressure and heart rate are recorded. Clinical events and side effects occurring since previous visit are recorded . It is up to the investigator to judge if visits are needed more frequently. However, no data will be collected at such extra visits.","PN","The study is a prospective, randomised, open trial with blinded\nclinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality.","NA",null,"NA",null,"Low","Low","The study is a prospective, randomised, open trial with blinded clinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality.",null,null,"PY","the final version of the protocol was approved in 1994, previous to the journal publication (1998) (L. Hansson & A. Zanchetti. The Hypertension Optimal Treatment (HOT) Study—Patient Characteristics: Randomization, Risk Profiles, and Early Blood Pressure Results. Blood Pressure Volume 3, 1994 - Issue 5).","N","The database shows all required results","N","The database shows all required results","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","there were some concerns in two domains"]
["2021/09/21 11.35",23,"JE","AASK","AASK 2002","Low targets","Standard targets","total mortality","RR=0.71","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","PY","Computer-based randomization","N","No significant imbalance in the flow chart","Low","Low","Computer-based randomization",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","In the publication authors do not explicitly state they perform an ITT analysis but they do it in practice and all outcomes are calculated with respect to the total number of randomized patients (JAMA. 2002;288:2421-2431).","NA",null,"Some concerns","Some concerns","open trial",null,null,"PY","patients lost to follow-up in study groups were 42/540 vs 47/554 (JAMA 2002;288:2421-2431).","NA",null,"NA",null,"NA",null,"Low","Low","No significant differences between groups",null,null,"PN","blood pressure measurement is correct and outcomes are determined according to standard methods (“The Rationale and Design of the AASK Cohort Study”, (J Am Soc Nephrol 14: S166–S172, 2003, section “Data Collection”). Data collection for exposures and outcomes are collected at baseline and every 12 mo thereafter. Management of anti-hypertensive therapy occurs at these visits and at an additional 2 to 4 visits per yr. Although participants are encouraged to receive their anti-hypertensive care through the AASK Cohort Study, some persons may decide not to accept such care. In this case, they are asked to attend just the semiannual data collection visits. Clinical outcomes are ascertained at each contact.\nThe pattern of data collection items and visits during all subsequent years is similar to that of year 2, except that ambulatory BP monitoring and echocardiography occur every other year. For those persons who reach ESRD during the Cohort Study, data collection visits still occur. BP is measured in a standardized fashion by trained, certified observers using the Tycos Classic Handheld Aneroid device. Two BP measurements are obtained in the seated position and one measurement in the upright position. All CVD procedures are done locally and read centrally by the Cardiovascular Procedures Core Laboratory at Lenox Hill Hospital. Each year, an ECG is obtained.\nSpecific codes of interest are the presence of LVH and myocardial infarction. At baseline and every other year, a two-dimensional, M-mode, pulsed Doppler and pulsed tissue Doppler echocardiogram is obtained to evaluate left ventricular (LV) structure, LV mass, cardiac output, and aortic valve structure; as well as to obtain measures of systolic and diastolic function.\nAt baseline and every other year, 24-h ambulatory BP recordings are obtained. The study uses the SpaceLabs 90217 Ultralite or SpaceLabs 90207 devices. During each 24-h recording, measurements are obtained every 30 min throughout the day and night, from which awake and asleep averages are calculated, along with other variables\nincluding dipping status.\n\n","NA","Interim visits will occur as frequently as necessary in between scheduled protocol follow-up visits. They may be for measurements for evaluation of protocol safety issues (e.g. Action Items, laboratory tests) or held electively. These visits will help ensure that participant's assigned MAP goals are achieved or maintained by adjustment of antihypertensive agents.","PN","All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalized cardiovascular events are reviewed and classified by a blinded endpoints committee according to a prespecified protocol.","NA",null,"NA",null,"Some concerns","Some concerns","Interim visits will occur as frequently as necessary in between scheduled protocol follow-up visits. They may be for measurements for evaluation of protocol safety issues (e.g. Action Items, laboratory tests) or held electively. These visits will help ensure that participant's assigned MAP goals are achieved or maintained by adjustment of antihypertensive agents. This is a matter of concern for being an open trial.",null,null,"PY","All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalized cardiovascular events were reviewed and classified by a blinded end\npoints committee according to a prespecified protocol. (“JAMA, November 20, 2002—Vol 288, No. 19, 2423”).\n","PN","The database shows all required results","PN","The database shows all required results","Low","Low","The database shows all required results",null,null,"Some concerns","Some concerns","there were some concerns in two domains"]
["2021/09/21 11.41",24,"JE","AASK","AASK 2002","Low targets","Standard targets","total serious adverse events","RR=0.94","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","PY","Computer-based randomization","N","No significant imbalance in the flow chart","Low","Low","Computer-based randomization",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","In the publication authors do not explicitly state they perform an ITT analysis but they do it in practice and all outcomes are calculated with respect to the total number of randomized patients (JAMA. 2002;288:2421-2431).","NA",null,"Some concerns","Some concerns","open trial",null,null,"PY","patients lost to follow-up in study groups were 42/540 vs 47/554 (JAMA 2002;288:2421-2431).","NA",null,"NA",null,"NA",null,"Low","Low","No significant differences between groups",null,null,"PN","blood pressure measurement is correct and outcomes are determined according to standard methods (“The Rationale and Design of the AASK Cohort Study”, (J Am Soc Nephrol 14: S166–S172, 2003, section “Data Collection”). Data collection for exposures and outcomes are collected at baseline and every 12 mo thereafter. Management of anti-hypertensive therapy occurs at these visits and at an additional 2 to 4 visits per yr. Although participants are encouraged to receive their anti-hypertensive care through the AASK Cohort Study, some persons may decide not to accept such care. In this case, they are asked to attend just the semiannual data collection visits. Clinical outcomes are ascertained at each contact.\nThe pattern of data collection items and visits during all subsequent years is similar to that of year 2, except that ambulatory BP monitoring and echocardiography occur every other year. For those persons who reach ESRD during the Cohort Study, data collection visits still occur. BP is measured in a standardized fashion by trained, certified observers using the Tycos Classic Handheld Aneroid device. Two BP measurements are obtained in the seated position and one measurement in the upright position. All CVD procedures are done locally and read centrally by the Cardiovascular Procedures Core Laboratory at Lenox Hill Hospital. Each year, an ECG is obtained.\nSpecific codes of interest are the presence of LVH and myocardial infarction. At baseline and every other year, a two-dimensional, M-mode, pulsed Doppler and pulsed tissue Doppler echocardiogram is obtained to evaluate left ventricular (LV) structure, LV mass, cardiac output, and aortic valve structure; as well as to obtain measures of systolic and diastolic function.\nAt baseline and every other year, 24-h ambulatory BP recordings are obtained. The study uses the SpaceLabs 90217 Ultralite or SpaceLabs 90207 devices. During each 24-h recording, measurements are obtained every 30 min throughout the day and night, from which awake and asleep averages are calculated, along with other variables\nincluding dipping status.\n\n","NA","Interim visits will occur as frequently as necessary in between scheduled protocol follow-up visits. They may be for measurements for evaluation of protocol safety issues (e.g. Action Items, laboratory tests) or held electively. These visits will help ensure that participant's assigned MAP goals are achieved or maintained by adjustment of antihypertensive agents.","PN","All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalized cardiovascular events are reviewed and classified by a blinded endpoints committee according to a prespecified protocol.","NA",null,"NA",null,"Some concerns","Some concerns","Interim visits will occur as frequently as necessary in between scheduled protocol follow-up visits. They may be for measurements for evaluation of protocol safety issues (e.g. Action Items, laboratory tests) or held electively. These visits will help ensure that participant's assigned MAP goals are achieved or maintained by adjustment of antihypertensive agents. This is a matter of concern for being an open trial.",null,null,"PY","All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalized cardiovascular events were reviewed and classified by a blinded end\npoints committee according to a prespecified protocol. (“JAMA, November 20, 2002—Vol 288, No. 19, 2423”).\n","PN","The database shows all required results","PN","The database shows all required results","Low","Low","The database shows all required results",null,null,"Some concerns","Some concerns","there were some concerns in two domains"]
["2021/09/21 11.45",25,"JE","AASK","AASK 2002","Low targets","Standard targets","total cardiovascular events","RR=1.02","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","PY","Computer-based randomization","N","No significant imbalance in the flow chart","Low","Low","Computer-based randomization",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","In the publication authors do not explicitly state they perform an ITT analysis but they do it in practice and all outcomes are calculated with respect to the total number of randomized patients (JAMA. 2002;288:2421-2431).","NA",null,"Some concerns","Some concerns","open trial",null,null,"PY","patients lost to follow-up in study groups were 42/540 vs 47/554 (JAMA 2002;288:2421-2431).","NA",null,"NA",null,"NA",null,"Low","Low","No significant differences between groups",null,null,"PN","blood pressure measurement is correct and outcomes are determined according to standard methods (“The Rationale and Design of the AASK Cohort Study”, (J Am Soc Nephrol 14: S166–S172, 2003, section “Data Collection”). Data collection for exposures and outcomes are collected at baseline and every 12 mo thereafter. Management of anti-hypertensive therapy occurs at these visits and at an additional 2 to 4 visits per yr. Although participants are encouraged to receive their anti-hypertensive care through the AASK Cohort Study, some persons may decide not to accept such care. In this case, they are asked to attend just the semiannual data collection visits. Clinical outcomes are ascertained at each contact.\nThe pattern of data collection items and visits during all subsequent years is similar to that of year 2, except that ambulatory BP monitoring and echocardiography occur every other year. For those persons who reach ESRD during the Cohort Study, data collection visits still occur. BP is measured in a standardized fashion by trained, certified observers using the Tycos Classic Handheld Aneroid device. Two BP measurements are obtained in the seated position and one measurement in the upright position. All CVD procedures are done locally and read centrally by the Cardiovascular Procedures Core Laboratory at Lenox Hill Hospital. Each year, an ECG is obtained.\nSpecific codes of interest are the presence of LVH and myocardial infarction. At baseline and every other year, a two-dimensional, M-mode, pulsed Doppler and pulsed tissue Doppler echocardiogram is obtained to evaluate left ventricular (LV) structure, LV mass, cardiac output, and aortic valve structure; as well as to obtain measures of systolic and diastolic function.\nAt baseline and every other year, 24-h ambulatory BP recordings are obtained. The study uses the SpaceLabs 90217 Ultralite or SpaceLabs 90207 devices. During each 24-h recording, measurements are obtained every 30 min throughout the day and night, from which awake and asleep averages are calculated, along with other variables\nincluding dipping status.\n\n","NA","Interim visits will occur as frequently as necessary in between scheduled protocol follow-up visits. They may be for measurements for evaluation of protocol safety issues (e.g. Action Items, laboratory tests) or held electively. These visits will help ensure that participant's assigned MAP goals are achieved or maintained by adjustment of antihypertensive agents.","PN","All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalized cardiovascular events are reviewed and classified by a blinded endpoints committee according to a prespecified protocol.","NA",null,"NA",null,"Some concerns","Some concerns","Interim visits will occur as frequently as necessary in between scheduled protocol follow-up visits. They may be for measurements for evaluation of protocol safety issues (e.g. Action Items, laboratory tests) or held electively. These visits will help ensure that participant's assigned MAP goals are achieved or maintained by adjustment of antihypertensive agents. This is a matter of concern for being an open trial.",null,null,"PY","All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalized cardiovascular events were reviewed and classified by a blinded end\npoints committee according to a prespecified protocol. (“JAMA, November 20, 2002—Vol 288, No. 19, 2423”).\n","PN","The database shows all required results","PN","The database shows all required results","Low","Low","The database shows all required results",null,null,"Some concerns","Some concerns","there were some concerns in two domains"]
["2021/09/21 11.49",26,"JE","AASK","AASK 2002","Low targets","Standard targets","cardiovascular mortality","RR=0.83","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","PY","Computer-based randomization","N","No significant imbalance in the flow chart","Low","Low","Computer-based randomization",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","In the publication authors do not explicitly state they perform an ITT analysis but they do it in practice and all outcomes are calculated with respect to the total number of randomized patients (JAMA. 2002;288:2421-2431).","NA",null,"Some concerns","Some concerns","open trial",null,null,"PY","patients lost to follow-up in study groups were 42/540 vs 47/554 (JAMA 2002;288:2421-2431).","NA",null,"NA",null,"NA",null,"Low","Low","No significant differences between groups",null,null,"PN","blood pressure measurement is correct and outcomes are determined according to standard methods (“The Rationale and Design of the AASK Cohort Study”, (J Am Soc Nephrol 14: S166–S172, 2003, section “Data Collection”). Data collection for exposures and outcomes are collected at baseline and every 12 mo thereafter. Management of anti-hypertensive therapy occurs at these visits and at an additional 2 to 4 visits per yr. Although participants are encouraged to receive their anti-hypertensive care through the AASK Cohort Study, some persons may decide not to accept such care. In this case, they are asked to attend just the semiannual data collection visits. Clinical outcomes are ascertained at each contact.\nThe pattern of data collection items and visits during all subsequent years is similar to that of year 2, except that ambulatory BP monitoring and echocardiography occur every other year. For those persons who reach ESRD during the Cohort Study, data collection visits still occur. BP is measured in a standardized fashion by trained, certified observers using the Tycos Classic Handheld Aneroid device. Two BP measurements are obtained in the seated position and one measurement in the upright position. All CVD procedures are done locally and read centrally by the Cardiovascular Procedures Core Laboratory at Lenox Hill Hospital. Each year, an ECG is obtained.\nSpecific codes of interest are the presence of LVH and myocardial infarction. At baseline and every other year, a two-dimensional, M-mode, pulsed Doppler and pulsed tissue Doppler echocardiogram is obtained to evaluate left ventricular (LV) structure, LV mass, cardiac output, and aortic valve structure; as well as to obtain measures of systolic and diastolic function.\nAt baseline and every other year, 24-h ambulatory BP recordings are obtained. The study uses the SpaceLabs 90217 Ultralite or SpaceLabs 90207 devices. During each 24-h recording, measurements are obtained every 30 min throughout the day and night, from which awake and asleep averages are calculated, along with other variables\nincluding dipping status.\n\n","NA","Interim visits will occur as frequently as necessary in between scheduled protocol follow-up visits. They may be for measurements for evaluation of protocol safety issues (e.g. Action Items, laboratory tests) or held electively. These visits will help ensure that participant's assigned MAP goals are achieved or maintained by adjustment of antihypertensive agents.","PN","All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalized cardiovascular events are reviewed and classified by a blinded endpoints committee according to a prespecified protocol.","NA",null,"NA",null,"Some concerns","Some concerns","Interim visits will occur as frequently as necessary in between scheduled protocol follow-up visits. They may be for measurements for evaluation of protocol safety issues (e.g. Action Items, laboratory tests) or held electively. These visits will help ensure that participant's assigned MAP goals are achieved or maintained by adjustment of antihypertensive agents. This is a matter of concern for being an open trial.",null,null,"PY","All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalized cardiovascular events were reviewed and classified by a blinded end\npoints committee according to a prespecified protocol. (“JAMA, November 20, 2002—Vol 288, No. 19, 2423”).\n","PN","The database shows all required results","PN","The database shows all required results","Low","Low","The database shows all required results",null,null,"Some concerns","Some concerns","there were some concerns in two domains"]
["2021/09/21 11.54",27,"JE","AASK","AASK 2002","Low targets","Standard targets","kidney failure","RR=0.98","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","PY","Computer-based randomization","N","No significant imbalance in the flow chart","Low","Low","Computer-based randomization",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","In the publication authors do not explicitly state they perform an ITT analysis but they do it in practice and all outcomes are calculated with respect to the total number of randomized patients (JAMA. 2002;288:2421-2431).","NA",null,"Some concerns","Some concerns","open trial",null,null,"PY","patients lost to follow-up in study groups were 42/540 vs 47/554 (JAMA 2002;288:2421-2431).","NA",null,"NA",null,"NA",null,"Low","Low","No significant differences between groups",null,null,"PN","blood pressure measurement is correct and outcomes are determined according to standard methods (“The Rationale and Design of the AASK Cohort Study”, (J Am Soc Nephrol 14: S166–S172, 2003, section “Data Collection”). Data collection for exposures and outcomes are collected at baseline and every 12 mo thereafter. Management of anti-hypertensive therapy occurs at these visits and at an additional 2 to 4 visits per yr. Although participants are encouraged to receive their anti-hypertensive care through the AASK Cohort Study, some persons may decide not to accept such care. In this case, they are asked to attend just the semiannual data collection visits. Clinical outcomes are ascertained at each contact.\nThe pattern of data collection items and visits during all subsequent years is similar to that of year 2, except that ambulatory BP monitoring and echocardiography occur every other year. For those persons who reach ESRD during the Cohort Study, data collection visits still occur. BP is measured in a standardized fashion by trained, certified observers using the Tycos Classic Handheld Aneroid device. Two BP measurements are obtained in the seated position and one measurement in the upright position. All CVD procedures are done locally and read centrally by the Cardiovascular Procedures Core Laboratory at Lenox Hill Hospital. Each year, an ECG is obtained.\nSpecific codes of interest are the presence of LVH and myocardial infarction. At baseline and every other year, a two-dimensional, M-mode, pulsed Doppler and pulsed tissue Doppler echocardiogram is obtained to evaluate left ventricular (LV) structure, LV mass, cardiac output, and aortic valve structure; as well as to obtain measures of systolic and diastolic function.\nAt baseline and every other year, 24-h ambulatory BP recordings are obtained. The study uses the SpaceLabs 90217 Ultralite or SpaceLabs 90207 devices. During each 24-h recording, measurements are obtained every 30 min throughout the day and night, from which awake and asleep averages are calculated, along with other variables\nincluding dipping status.\n\n","NA","Interim visits will occur as frequently as necessary in between scheduled protocol follow-up visits. They may be for measurements for evaluation of protocol safety issues (e.g. Action Items, laboratory tests) or held electively. These visits will help ensure that participant's assigned MAP goals are achieved or maintained by adjustment of antihypertensive agents.","PN","All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalized cardiovascular events are reviewed and classified by a blinded endpoints committee according to a prespecified protocol.","NA",null,"NA",null,"Some concerns","Some concerns","Interim visits will occur as frequently as necessary in between scheduled protocol follow-up visits. They may be for measurements for evaluation of protocol safety issues (e.g. Action Items, laboratory tests) or held electively. These visits will help ensure that participant's assigned MAP goals are achieved or maintained by adjustment of antihypertensive agents. This is a matter of concern for being an open trial.",null,null,"PY","All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalized cardiovascular events were reviewed and classified by a blinded end\npoints committee according to a prespecified protocol. (“JAMA, November 20, 2002—Vol 288, No. 19, 2423”).\n","PN","The database shows all required results","PN","The database shows all required results","Low","Low","The database shows all required results",null,null,"Some concerns","Some concerns","there were some concerns in two domains"]
["2021/09/21 12.00",28,"JE","AASK","AASK 2002","Low targets","Standard targets","Participant withdrawals due to adverse effects",null,null,null,null,null,null,null,null,null,null,null,null,"Computer-based randomization"]
["2021/09/21 12.11",29,"JE","AASK","AASK 2002","Low targets","Standard targets","Systolic blood pressure difference from baseline at one year","MD=13.80","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","PY","Computer-based randomization","N","No significant imbalance in the flow chart","Low","Low","Computer-based randomization",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","In the publication authors do not explicitly state they perform an ITT analysis but they do it in practice and all outcomes are calculated with respect to the total number of randomized patients (JAMA. 2002;288:2421-2431).","NA",null,"Some concerns","Some concerns","open trial",null,null,"PY","patients lost to follow-up in study groups were 42/540 vs 47/554 (JAMA 2002;288:2421-2431).","NA",null,"NA",null,"NA",null,"Low","Low","No significant differences between groups",null,null,"PN","blood pressure measurement is correct and outcomes are determined according to standard methods (“The Rationale and Design of the AASK Cohort Study”, (J Am Soc Nephrol 14: S166–S172, 2003, section “Data Collection”). Data collection for exposures and outcomes are collected at baseline and every 12 mo thereafter. Management of anti-hypertensive therapy occurs at these visits and at an additional 2 to 4 visits per yr. Although participants are encouraged to receive their anti-hypertensive care through the AASK Cohort Study, some persons may decide not to accept such care. In this case, they are asked to attend just the semiannual data collection visits. Clinical outcomes are ascertained at each contact.\nThe pattern of data collection items and visits during all subsequent years is similar to that of year 2, except that ambulatory BP monitoring and echocardiography occur every other year. For those persons who reach ESRD during the Cohort Study, data collection visits still occur. BP is measured in a standardized fashion by trained, certified observers using the Tycos Classic Handheld Aneroid device. Two BP measurements are obtained in the seated position and one measurement in the upright position. All CVD procedures are done locally and read centrally by the Cardiovascular Procedures Core Laboratory at Lenox Hill Hospital. Each year, an ECG is obtained.\nSpecific codes of interest are the presence of LVH and myocardial infarction. At baseline and every other year, a two-dimensional, M-mode, pulsed Doppler and pulsed tissue Doppler echocardiogram is obtained to evaluate left ventricular (LV) structure, LV mass, cardiac output, and aortic valve structure; as well as to obtain measures of systolic and diastolic function.\nAt baseline and every other year, 24-h ambulatory BP recordings are obtained. The study uses the SpaceLabs 90217 Ultralite or SpaceLabs 90207 devices. During each 24-h recording, measurements are obtained every 30 min throughout the day and night, from which awake and asleep averages are calculated, along with other variables\nincluding dipping status.\n\n","NA","Interim visits will occur as frequently as necessary in between scheduled protocol follow-up visits. They may be for measurements for evaluation of protocol safety issues (e.g. Action Items, laboratory tests) or held electively. These visits will help ensure that participant's assigned MAP goals are achieved or maintained by adjustment of antihypertensive agents.","PN","All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalized cardiovascular events are reviewed and classified by a blinded endpoints committee according to a prespecified protocol.","NA",null,"NA",null,"Some concerns","Some concerns","Interim visits will occur as frequently as necessary in between scheduled protocol follow-up visits. They may be for measurements for evaluation of protocol safety issues (e.g. Action Items, laboratory tests) or held electively. These visits will help ensure that participant's assigned MAP goals are achieved or maintained by adjustment of antihypertensive agents. This is a matter of concern for being an open trial.",null,null,"PY","All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalized cardiovascular events were reviewed and classified by a blinded end\npoints committee according to a prespecified protocol. (“JAMA, November 20, 2002—Vol 288, No. 19, 2423”).\n","PN","The database shows all required results","PN","The database shows all required results","Low","Low","The database shows all required results",null,null,"Some concerns","Some concerns","there were some concerns in two domains"]
["2021/09/21 12.16",30,"JE","AASK","AASK 2002","Low targets","Standard targets","Diastolic blood pressure difference from baseline at one year","MD=9.30","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","PY","Computer-based randomization","N","No significant imbalance in the flow chart","Low","Low","Computer-based randomization",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","In the publication authors do not explicitly state they perform an ITT analysis but they do it in practice and all outcomes are calculated with respect to the total number of randomized patients (JAMA. 2002;288:2421-2431).","NA",null,"Some concerns","Some concerns","open trial",null,null,"PY","patients lost to follow-up in study groups were 42/540 vs 47/554 (JAMA 2002;288:2421-2431).","NA",null,"NA",null,"NA",null,"Low","Low","No significant differences between groups",null,null,"PN","blood pressure measurement is correct and outcomes are determined according to standard methods (“The Rationale and Design of the AASK Cohort Study”, (J Am Soc Nephrol 14: S166–S172, 2003, section “Data Collection”). Data collection for exposures and outcomes are collected at baseline and every 12 mo thereafter. Management of anti-hypertensive therapy occurs at these visits and at an additional 2 to 4 visits per yr. Although participants are encouraged to receive their anti-hypertensive care through the AASK Cohort Study, some persons may decide not to accept such care. In this case, they are asked to attend just the semiannual data collection visits. Clinical outcomes are ascertained at each contact.\nThe pattern of data collection items and visits during all subsequent years is similar to that of year 2, except that ambulatory BP monitoring and echocardiography occur every other year. For those persons who reach ESRD during the Cohort Study, data collection visits still occur. BP is measured in a standardized fashion by trained, certified observers using the Tycos Classic Handheld Aneroid device. Two BP measurements are obtained in the seated position and one measurement in the upright position. All CVD procedures are done locally and read centrally by the Cardiovascular Procedures Core Laboratory at Lenox Hill Hospital. Each year, an ECG is obtained.\nSpecific codes of interest are the presence of LVH and myocardial infarction. At baseline and every other year, a two-dimensional, M-mode, pulsed Doppler and pulsed tissue Doppler echocardiogram is obtained to evaluate left ventricular (LV) structure, LV mass, cardiac output, and aortic valve structure; as well as to obtain measures of systolic and diastolic function.\nAt baseline and every other year, 24-h ambulatory BP recordings are obtained. The study uses the SpaceLabs 90217 Ultralite or SpaceLabs 90207 devices. During each 24-h recording, measurements are obtained every 30 min throughout the day and night, from which awake and asleep averages are calculated, along with other variables\nincluding dipping status.\n\n","NA","Interim visits will occur as frequently as necessary in between scheduled protocol follow-up visits. They may be for measurements for evaluation of protocol safety issues (e.g. Action Items, laboratory tests) or held electively. These visits will help ensure that participant's assigned MAP goals are achieved or maintained by adjustment of antihypertensive agents.","PN","All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalized cardiovascular events are reviewed and classified by a blinded endpoints committee according to a prespecified protocol.","NA",null,"NA",null,"Some concerns","Some concerns","Interim visits will occur as frequently as necessary in between scheduled protocol follow-up visits. They may be for measurements for evaluation of protocol safety issues (e.g. Action Items, laboratory tests) or held electively. These visits will help ensure that participant's assigned MAP goals are achieved or maintained by adjustment of antihypertensive agents. This is a matter of concern for being an open trial.",null,null,"PY","All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalized cardiovascular events were reviewed and classified by a blinded end\npoints committee according to a prespecified protocol. (“JAMA, November 20, 2002—Vol 288, No. 19, 2423”).\n","PN","The database shows all required results","PN","The database shows all required results","Low","Low","The database shows all required results",null,null,"Some concerns","Some concerns","there were some concerns in two domains"]
["2021/09/21 12.21",31,"JE","AASK","AASK 2002","Low targets","Standard targets","Doubling of serum creatinine level or 50% reduction in GFR at the end of study","RR=1.53","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","PY","Computer-based randomization","N","No significant imbalance in the flow chart","Low","Low","Computer-based randomization",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","In the publication authors do not explicitly state they perform an ITT analysis but they do it in practice and all outcomes are calculated with respect to the total number of randomized patients (JAMA. 2002;288:2421-2431).","NA",null,"Some concerns","Some concerns","open trial",null,null,"PY","patients lost to follow-up in study groups were 42/540 vs 47/554 (JAMA 2002;288:2421-2431).","NA",null,"NA",null,"NA",null,"Low","Low","No significant differences between groups",null,null,"PN","blood pressure measurement is correct and outcomes are determined according to standard methods (“The Rationale and Design of the AASK Cohort Study”, (J Am Soc Nephrol 14: S166–S172, 2003, section “Data Collection”). Data collection for exposures and outcomes are collected at baseline and every 12 mo thereafter. Management of anti-hypertensive therapy occurs at these visits and at an additional 2 to 4 visits per yr. Although participants are encouraged to receive their anti-hypertensive care through the AASK Cohort Study, some persons may decide not to accept such care. In this case, they are asked to attend just the semiannual data collection visits. Clinical outcomes are ascertained at each contact.\nThe pattern of data collection items and visits during all subsequent years is similar to that of year 2, except that ambulatory BP monitoring and echocardiography occur every other year. For those persons who reach ESRD during the Cohort Study, data collection visits still occur. BP is measured in a standardized fashion by trained, certified observers using the Tycos Classic Handheld Aneroid device. Two BP measurements are obtained in the seated position and one measurement in the upright position. All CVD procedures are done locally and read centrally by the Cardiovascular Procedures Core Laboratory at Lenox Hill Hospital. Each year, an ECG is obtained.\nSpecific codes of interest are the presence of LVH and myocardial infarction. At baseline and every other year, a two-dimensional, M-mode, pulsed Doppler and pulsed tissue Doppler echocardiogram is obtained to evaluate left ventricular (LV) structure, LV mass, cardiac output, and aortic valve structure; as well as to obtain measures of systolic and diastolic function.\nAt baseline and every other year, 24-h ambulatory BP recordings are obtained. The study uses the SpaceLabs 90217 Ultralite or SpaceLabs 90207 devices. During each 24-h recording, measurements are obtained every 30 min throughout the day and night, from which awake and asleep averages are calculated, along with other variables\nincluding dipping status.\n\n","NA","Interim visits will occur as frequently as necessary in between scheduled protocol follow-up visits. They may be for measurements for evaluation of protocol safety issues (e.g. Action Items, laboratory tests) or held electively. These visits will help ensure that participant's assigned MAP goals are achieved or maintained by adjustment of antihypertensive agents.","PN","All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalized cardiovascular events are reviewed and classified by a blinded endpoints committee according to a prespecified protocol.","NA",null,"NA",null,"Some concerns","Some concerns","Interim visits will occur as frequently as necessary in between scheduled protocol follow-up visits. They may be for measurements for evaluation of protocol safety issues (e.g. Action Items, laboratory tests) or held electively. These visits will help ensure that participant's assigned MAP goals are achieved or maintained by adjustment of antihypertensive agents. This is a matter of concern for being an open trial.",null,null,"PY","All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalized cardiovascular events were reviewed and classified by a blinded end\npoints committee according to a prespecified protocol. (“JAMA, November 20, 2002—Vol 288, No. 19, 2423”).\n","PN","The database shows all required results","PN","The database shows all required results","Low","Low","The database shows all required results",null,null,"Some concerns","Some concerns","there were some concerns in two domains"]
["2021/09/21 12.27",32,"JE","AASK","AASK 2002","Low targets","Standard targets","Proportion of participants reaching target levels of blood pressure at the end of study","RR=1.68","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","PY","Computer-based randomization","N","No significant imbalance in the flow chart","Low","Low","Computer-based randomization",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","In the publication authors do not explicitly state they perform an ITT analysis but they do it in practice and all outcomes are calculated with respect to the total number of randomized patients (JAMA. 2002;288:2421-2431).","NA",null,"Some concerns","Some concerns","open trial",null,null,"PY","patients lost to follow-up in study groups were 42/540 vs 47/554 (JAMA 2002;288:2421-2431).","NA",null,"NA",null,"NA",null,"Low","Low","No significant differences between groups.",null,null,"PN","blood pressure measurement is correct and outcomes are determined according to standard methods (“The Rationale and Design of the AASK Cohort Study”, (J Am Soc Nephrol 14: S166–S172, 2003, section “Data Collection”). Data collection for exposures and outcomes are collected at baseline and every 12 mo thereafter. Management of anti-hypertensive therapy occurs at these visits and at an additional 2 to 4 visits per yr. Although participants are encouraged to receive their anti-hypertensive care through the AASK Cohort Study, some persons may decide not to accept such care. In this case, they are asked to attend just the semiannual data collection visits. Clinical outcomes are ascertained at each contact.\nThe pattern of data collection items and visits during all subsequent years is similar to that of year 2, except that ambulatory BP monitoring and echocardiography occur every other year. For those persons who reach ESRD during the Cohort Study, data collection visits still occur. BP is measured in a standardized fashion by trained, certified observers using the Tycos Classic Handheld Aneroid device. Two BP measurements are obtained in the seated position and one measurement in the upright position. All CVD procedures are done locally and read centrally by the Cardiovascular Procedures Core Laboratory at Lenox Hill Hospital. Each year, an ECG is obtained.\nSpecific codes of interest are the presence of LVH and myocardial infarction. At baseline and every other year, a two-dimensional, M-mode, pulsed Doppler and pulsed tissue Doppler echocardiogram is obtained to evaluate left ventricular (LV) structure, LV mass, cardiac output, and aortic valve structure; as well as to obtain measures of systolic and diastolic function.\nAt baseline and every other year, 24-h ambulatory BP recordings are obtained. The study uses the SpaceLabs 90217 Ultralite or SpaceLabs 90207 devices. During each 24-h recording, measurements are obtained every 30 min throughout the day and night, from which awake and asleep averages are calculated, along with other variables\nincluding dipping status.\n\n","NA","Interim visits will occur as frequently as necessary in between scheduled protocol follow-up visits. They may be for measurements for evaluation of protocol safety issues (e.g. Action Items, laboratory tests) or held electively. These visits will help ensure that participant's assigned MAP goals are achieved or maintained by adjustment of antihypertensive agents.","PN","All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalized cardiovascular events are reviewed and classified by a blinded endpoints committee according to a prespecified protocol.","NA",null,"NA",null,"Some concerns","Some concerns","Interim visits will occur as frequently as necessary in between scheduled protocol follow-up visits. They may be for measurements for evaluation of protocol safety issues (e.g. Action Items, laboratory tests) or held electively. These visits will help ensure that participant's assigned MAP goals are achieved or maintained by adjustment of antihypertensive agents. This is a matter of concern for being an open trial.",null,null,"PY","All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalized cardiovascular events were reviewed and classified by a blinded end\npoints committee according to a prespecified protocol. (“JAMA, November 20, 2002—Vol 288, No. 19, 2423”).\n","PN","The database shows all required results","PN","The database shows all required results","Low","Low","The database shows all required results",null,null,"Some concerns","Some concerns","there were some concerns in two domains"]
["2021/09/21 12.33",33,"JE","AASK","AASK 2002","Low targets","Standard targets","Number of antihypertensive drugs that each participant needed at the end of study",null,null,null,null,null,null,null,null,null,null,null,null,"Computer-based randomization"]
["2021/09/21 12.39",34,"JE","SPRINT","SPRINT 2015","Low targets","Standard targets","total mortality","RR=0.74","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","PY","SPRINT will use an internet-based, web browser randomization procedure. ","N","No significant imbalance in the flow chart","Low","Low","SPRINT will use an internet-based, web browser randomization procedure. ",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","Our primary analysis compared the time to the first occurrence of a primary outcome event between the two study groups with the use of the intention-to-treat approach for all randomly assigned participants (NEJM, DOI: 10.1056/NEJMoa1511939).","NA",null,"Some concerns","Some concerns","open trial",null,null,"Y","patients lost to follow-up in study groups were 111/4678 vs 134/4683   (NEJM, DOI: 10.1056/NEJMoa1511939).","NA",null,"NA",null,"NA",null,"Low","Low","No significant differences between groups.",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (NEJM, DOI: 10.1056/NEJMoa1511939, Protocol and Supplementary Appendix). Standing BP will be measured at screening, baseline, 1 month, 6 months, 12 months, and annually thereafter using the same BP device that is used to measure seated BP. After seated determinations, participants will be asked to stand. Beginning when their feet touch the floor, BP will be taken one minute later in the same arm used for the seated measurements, using the BP device. Participants will be asked after the standing determination if they had any symptoms of orthostatic hypotension during the standing BP measurement. The Coordinating Center will calculate BP change using the standing measurements minus the mean of the seated measurements.\n5.3.1 Seated Blood Pressure and Pulse\nSeated blood pressure and pulse are measured at each clinic visit after a rest period using an automated device or manual devises if necessary. The preferred method is the automated device as it offers reduced potential for observer biases and decreased demand on staff in terms of training and effort in data collection.\n5.4.7 Study-related outcomes\nBoth randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3\nmonths for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use\navailable resources and contact information to assess vital status annually on participants not attending study visits.\n","PN","At each quarterly visit, SPRINT staff will specifically query participants for serious adverse events. In addition, information on serious adverse events may also be reported to study staff spontaneously by participants through telephone calls or emails between study visits. In addition to local reporting requirements, all serious adverse events will be recorded by clinic staff and forwarded to the CC Medical Safety Officer within 72 hours of knowledge of the event. SAEs will be collected and reported from screening to the end of the study follow-up period for an individual participant.","NA","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not.","NA",null,"PN",null,"low","low","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not.",null,null,"PY","the design and protocol were published in advance: Systolic Blood Pressure Intervention Trial (SPRINT) protocol. November 1, 2012 (https://www.sprinttrial.org/ public/Protocol_Current.pdf), and also Ambrosius WT, et al. The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: the Systolic Blood Pressure Intervention Trial (SPRINT). Clin Trials 2014; 11: 532-46. ","PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits.","PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits.","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","There were some concerns in one domain."]
["2021/09/21 12.45",35,"JE","SPRINT","SPRINT 2015","Low targets","Standard targets","total serious adverse events","RR=0.97","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","PY","SPRINT will use an internet-based, web browser randomization procedure. ","N","No significant imbalance in the flow chart","Low","Low","SPRINT will use an internet-based, web browser randomization procedure. ",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","Our primary analysis compared the time to the first occurrence of a primary outcome event between the two study groups with the use of the intention-to-treat approach for all randomly assigned participants (NEJM, DOI: 10.1056/NEJMoa1511939).","NA",null,"Some concerns","Some concerns","open trial",null,null,"Y","patients lost to follow-up in study groups were 111/4678 vs 134/4683   (NEJM, DOI: 10.1056/NEJMoa1511939).","NA",null,"NA",null,"NA",null,"Low","Low","No significant differences between groups.",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (NEJM, DOI: 10.1056/NEJMoa1511939, Protocol and Supplementary Appendix). Standing BP will be measured at screening, baseline, 1 month, 6 months, 12 months, and annually thereafter using the same BP device that is used to measure seated BP. After seated determinations, participants will be asked to stand. Beginning when their feet touch the floor, BP will be taken one minute later in the same arm used for the seated measurements, using the BP device. Participants will be asked after the standing determination if they had any symptoms of orthostatic hypotension during the standing BP measurement. The Coordinating Center will calculate BP change using the standing measurements minus the mean of the seated measurements.\n5.3.1 Seated Blood Pressure and Pulse\nSeated blood pressure and pulse are measured at each clinic visit after a rest period using an automated device or manual devises if necessary. The preferred method is the automated device as it offers reduced potential for observer biases and decreased demand on staff in terms of training and effort in data collection.\n5.4.7 Study-related outcomes\nBoth randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3\nmonths for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use\navailable resources and contact information to assess vital status annually on participants not attending study visits.\n","PN","At each quarterly visit, SPRINT staff will specifically query participants for serious adverse events. In addition, information on serious adverse events may also be reported to study staff spontaneously by participants through telephone calls or emails between study visits. In addition to local reporting requirements, all serious adverse events will be recorded by clinic staff and forwarded to the CC Medical Safety Officer within 72 hours of knowledge of the event. SAEs will be collected and reported from screening to the end of the study follow-up period for an individual participant.","NA","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not.","NA",null,"PN",null,"low","low","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not.",null,null,"PY","the design and protocol were published in advance: Systolic Blood Pressure Intervention Trial (SPRINT) protocol. November 1, 2012 (https://www.sprinttrial.org/ public/Protocol_Current.pdf), and also Ambrosius WT, et al. The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: the Systolic Blood Pressure Intervention Trial (SPRINT). Clin Trials 2014; 11: 532-46. ","PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits.","PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits.","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","There were some concerns in one domain."]
["2021/09/21 12.56",36,"JE","SPRINT","SPRINT 2015","Low targets","Standard targets","total cardiovascular events","RR=0.83","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","PY","SPRINT will use an internet-based, web browser randomization procedure. ","N","No significant imbalance in the flow chart","Low","Low","SPRINT will use an internet-based, web browser randomization procedure. ",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","Our primary analysis compared the time to the first occurrence of a primary outcome event between the two study groups with the use of the intention-to-treat approach for all randomly assigned participants (NEJM, DOI: 10.1056/NEJMoa1511939).","NA",null,"Some concerns","Some concerns","open trial",null,null,"Y","patients lost to follow-up in study groups were 111/4678 vs 134/4683   (NEJM, DOI: 10.1056/NEJMoa1511939).","NA",null,"NA",null,"NA",null,"Low","Low","No significant differences between groups.",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (NEJM, DOI: 10.1056/NEJMoa1511939, Protocol and Supplementary Appendix). Standing BP will be measured at screening, baseline, 1 month, 6 months, 12 months, and annually thereafter using the same BP device that is used to measure seated BP. After seated determinations, participants will be asked to stand. Beginning when their feet touch the floor, BP will be taken one minute later in the same arm used for the seated measurements, using the BP device. Participants will be asked after the standing determination if they had any symptoms of orthostatic hypotension during the standing BP measurement. The Coordinating Center will calculate BP change using the standing measurements minus the mean of the seated measurements.\n5.3.1 Seated Blood Pressure and Pulse\nSeated blood pressure and pulse are measured at each clinic visit after a rest period using an automated device or manual devises if necessary. The preferred method is the automated device as it offers reduced potential for observer biases and decreased demand on staff in terms of training and effort in data collection.\n5.4.7 Study-related outcomes\nBoth randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3\nmonths for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use\navailable resources and contact information to assess vital status annually on participants not attending study visits.\n","PN","At each quarterly visit, SPRINT staff will specifically query participants for serious adverse events. In addition, information on serious adverse events may also be reported to study staff spontaneously by participants through telephone calls or emails between study visits. In addition to local reporting requirements, all serious adverse events will be recorded by clinic staff and forwarded to the CC Medical Safety Officer within 72 hours of knowledge of the event. SAEs will be collected and reported from screening to the end of the study follow-up period for an individual participant.","NA","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not.","NA",null,"PN",null,"low","low","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not.",null,null,"PY","the design and protocol were published in advance: Systolic Blood Pressure Intervention Trial (SPRINT) protocol. November 1, 2012 (https://www.sprinttrial.org/ public/Protocol_Current.pdf), and also Ambrosius WT, et al. The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: the Systolic Blood Pressure Intervention Trial (SPRINT). Clin Trials 2014; 11: 532-46. ","PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits.","PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits.","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","There were some concerns in one domain."]
["2021/09/21 13.08",37,"JE","SPRINT","SPRINT 2015","Low targets","Standard targets","cardiovascular mortality","RR=0.61","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","PY","SPRINT will use an internet-based, web browser randomization procedure. ","N","No significant imbalance in the flow chart","Low","Low","SPRINT will use an internet-based, web browser randomization procedure. ",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","Our primary analysis compared the time to the first occurrence of a primary outcome event between the two study groups with the use of the intention-to-treat approach for all randomly assigned participants (NEJM, DOI: 10.1056/NEJMoa1511939).","NA",null,"Some concerns","Some concerns","open trial",null,null,"Y","patients lost to follow-up in study groups were 111/4678 vs 134/4683   (NEJM, DOI: 10.1056/NEJMoa1511939).","NA",null,"NA",null,"NA",null,"Low","Low","No significant differences between groups.",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (NEJM, DOI: 10.1056/NEJMoa1511939, Protocol and Supplementary Appendix). Standing BP will be measured at screening, baseline, 1 month, 6 months, 12 months, and annually thereafter using the same BP device that is used to measure seated BP. After seated determinations, participants will be asked to stand. Beginning when their feet touch the floor, BP will be taken one minute later in the same arm used for the seated measurements, using the BP device. Participants will be asked after the standing determination if they had any symptoms of orthostatic hypotension during the standing BP measurement. The Coordinating Center will calculate BP change using the standing measurements minus the mean of the seated measurements.\n5.3.1 Seated Blood Pressure and Pulse\nSeated blood pressure and pulse are measured at each clinic visit after a rest period using an automated device or manual devises if necessary. The preferred method is the automated device as it offers reduced potential for observer biases and decreased demand on staff in terms of training and effort in data collection.\n5.4.7 Study-related outcomes\nBoth randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3\nmonths for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use\navailable resources and contact information to assess vital status annually on participants not attending study visits.\n","PN","At each quarterly visit, SPRINT staff will specifically query participants for serious adverse events. In addition, information on serious adverse events may also be reported to study staff spontaneously by participants through telephone calls or emails between study visits. In addition to local reporting requirements, all serious adverse events will be recorded by clinic staff and forwarded to the CC Medical Safety Officer within 72 hours of knowledge of the event. SAEs will be collected and reported from screening to the end of the study follow-up period for an individual participant.","NA","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not.","NA",null,"PN",null,"low","low","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not.",null,null,"PY","the design and protocol were published in advance: Systolic Blood Pressure Intervention Trial (SPRINT) protocol. November 1, 2012 (https://www.sprinttrial.org/ public/Protocol_Current.pdf), and also Ambrosius WT, et al. The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: the Systolic Blood Pressure Intervention Trial (SPRINT). Clin Trials 2014; 11: 532-46. ","PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits.","PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits.","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","There were some concerns in one domain."]
["2021/09/21 13.16",38,"JE","SPRINT","SPRINT 2015","Low targets","Standard targets","kidney failure","RR=0.59","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","PY","SPRINT will use an internet-based, web browser randomization procedure. ","N","No significant imbalance in the flow chart","Low","Low","SPRINT will use an internet-based, web browser randomization procedure. ",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","Our primary analysis compared the time to the first occurrence of a primary outcome event between the two study groups with the use of the intention-to-treat approach for all randomly assigned participants (NEJM, DOI: 10.1056/NEJMoa1511939).","NA",null,"Some concerns","Some concerns","open trial",null,null,"Y","patients lost to follow-up in study groups were 111/4678 vs 134/4683   (NEJM, DOI: 10.1056/NEJMoa1511939).","NA",null,"NA",null,"NA",null,"Low","Low","No significant differences between groups.",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (NEJM, DOI: 10.1056/NEJMoa1511939, Protocol and Supplementary Appendix). Standing BP will be measured at screening, baseline, 1 month, 6 months, 12 months, and annually thereafter using the same BP device that is used to measure seated BP. After seated determinations, participants will be asked to stand. Beginning when their feet touch the floor, BP will be taken one minute later in the same arm used for the seated measurements, using the BP device. Participants will be asked after the standing determination if they had any symptoms of orthostatic hypotension during the standing BP measurement. The Coordinating Center will calculate BP change using the standing measurements minus the mean of the seated measurements.\n5.3.1 Seated Blood Pressure and Pulse\nSeated blood pressure and pulse are measured at each clinic visit after a rest period using an automated device or manual devises if necessary. The preferred method is the automated device as it offers reduced potential for observer biases and decreased demand on staff in terms of training and effort in data collection.\n5.4.7 Study-related outcomes\nBoth randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3\nmonths for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use\navailable resources and contact information to assess vital status annually on participants not attending study visits.\n","PN","At each quarterly visit, SPRINT staff will specifically query participants for serious adverse events. In addition, information on serious adverse events may also be reported to study staff spontaneously by participants through telephone calls or emails between study visits. In addition to local reporting requirements, all serious adverse events will be recorded by clinic staff and forwarded to the CC Medical Safety Officer within 72 hours of knowledge of the event. SAEs will be collected and reported from screening to the end of the study follow-up period for an individual participant.","NA","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not.","NA",null,"PN",null,"low","low","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not.",null,null,"PY","the design and protocol were published in advance: Systolic Blood Pressure Intervention Trial (SPRINT) protocol. November 1, 2012 (https://www.sprinttrial.org/ public/Protocol_Current.pdf), and also Ambrosius WT, et al. The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: the Systolic Blood Pressure Intervention Trial (SPRINT). Clin Trials 2014; 11: 532-46. ","PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits.","PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits.","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","There were some concerns in one domain."]
["2021/09/21 13.27",39,"JE","SPRINT","SPRINT 2015","Low targets","Standard targets","Participant withdrawals due to adverse effects",null,null,null,null,null,null,null,null,null,null,null,null,"SPRINT will use an internet-based, web browser randomization procedure. ",null,null,"-"]
["2021/09/21 13.35",40,"JE","SPRINT","SPRINT 2015","Low targets","Standard targets","Systolic blood pressure difference from baseline at one year","MD=13.18","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","PY","SPRINT will use an internet-based, web browser randomization procedure. ","N","No significant imbalance in the flow chart","Low","Low","SPRINT will use an internet-based, web browser randomization procedure. ",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","Our primary analysis compared the time to the first occurrence of a primary outcome event between the two study groups with the use of the intention-to-treat approach for all randomly assigned participants (NEJM, DOI: 10.1056/NEJMoa1511939).","NA",null,"Some concerns","Some concerns","open trial",null,null,"Y","patients lost to follow-up in study groups were 111/4678 vs 134/4683   (NEJM, DOI: 10.1056/NEJMoa1511939).","NA",null,"NA",null,"NA",null,"Low","Low","No significant differences between groups.",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (NEJM, DOI: 10.1056/NEJMoa1511939, Protocol and Supplementary Appendix). Standing BP will be measured at screening, baseline, 1 month, 6 months, 12 months, and annually thereafter using the same BP device that is used to measure seated BP. After seated determinations, participants will be asked to stand. Beginning when their feet touch the floor, BP will be taken one minute later in the same arm used for the seated measurements, using the BP device. Participants will be asked after the standing determination if they had any symptoms of orthostatic hypotension during the standing BP measurement. The Coordinating Center will calculate BP change using the standing measurements minus the mean of the seated measurements.\n5.3.1 Seated Blood Pressure and Pulse\nSeated blood pressure and pulse are measured at each clinic visit after a rest period using an automated device or manual devises if necessary. The preferred method is the automated device as it offers reduced potential for observer biases and decreased demand on staff in terms of training and effort in data collection.\n5.4.7 Study-related outcomes\nBoth randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3\nmonths for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use\navailable resources and contact information to assess vital status annually on participants not attending study visits.\n","PN","At each quarterly visit, SPRINT staff will specifically query participants for serious adverse events. In addition, information on serious adverse events may also be reported to study staff spontaneously by participants through telephone calls or emails between study visits. In addition to local reporting requirements, all serious adverse events will be recorded by clinic staff and forwarded to the CC Medical Safety Officer within 72 hours of knowledge of the event. SAEs will be collected and reported from screening to the end of the study follow-up period for an individual participant.","NA","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not.","NA",null,"PN",null,"low","low","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not.",null,null,"PY","the design and protocol were published in advance: Systolic Blood Pressure Intervention Trial (SPRINT) protocol. November 1, 2012 (https://www.sprinttrial.org/ public/Protocol_Current.pdf), and also Ambrosius WT, et al. The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: the Systolic Blood Pressure Intervention Trial (SPRINT). Clin Trials 2014; 11: 532-46. ","PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits.","PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits.","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","There were some concerns in one domain."]
["2021/09/21 13.41",41,"JE","SPRINT","SPRINT 2015","Low targets","Standard targets","Diastolic blood pressure difference from baseline at one year","MD=7.42","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","PY","SPRINT will use an internet-based, web browser randomization procedure. ","N","No significant imbalance in the flow chart","Low","Low","SPRINT will use an internet-based, web browser randomization procedure. ",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","Our primary analysis compared the time to the first occurrence of a primary outcome event between the two study groups with the use of the intention-to-treat approach for all randomly assigned participants (NEJM, DOI: 10.1056/NEJMoa1511939).","NA",null,"Some concerns","Some concerns","open trial",null,null,"Y","patients lost to follow-up in study groups were 111/4678 vs 134/4683   (NEJM, DOI: 10.1056/NEJMoa1511939).","NA",null,"NA",null,"NA",null,"Low","Low","No significant differences between groups.",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (NEJM, DOI: 10.1056/NEJMoa1511939, Protocol and Supplementary Appendix). Standing BP will be measured at screening, baseline, 1 month, 6 months, 12 months, and annually thereafter using the same BP device that is used to measure seated BP. After seated determinations, participants will be asked to stand. Beginning when their feet touch the floor, BP will be taken one minute later in the same arm used for the seated measurements, using the BP device. Participants will be asked after the standing determination if they had any symptoms of orthostatic hypotension during the standing BP measurement. The Coordinating Center will calculate BP change using the standing measurements minus the mean of the seated measurements.\n5.3.1 Seated Blood Pressure and Pulse\nSeated blood pressure and pulse are measured at each clinic visit after a rest period using an automated device or manual devises if necessary. The preferred method is the automated device as it offers reduced potential for observer biases and decreased demand on staff in terms of training and effort in data collection.\n5.4.7 Study-related outcomes\nBoth randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3\nmonths for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use\navailable resources and contact information to assess vital status annually on participants not attending study visits.\n","PN","At each quarterly visit, SPRINT staff will specifically query participants for serious adverse events. In addition, information on serious adverse events may also be reported to study staff spontaneously by participants through telephone calls or emails between study visits. In addition to local reporting requirements, all serious adverse events will be recorded by clinic staff and forwarded to the CC Medical Safety Officer within 72 hours of knowledge of the event. SAEs will be collected and reported from screening to the end of the study follow-up period for an individual participant.","NA","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not.","NA",null,"PN",null,"low","low","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not.",null,null,"PY","the design and protocol were published in advance: Systolic Blood Pressure Intervention Trial (SPRINT) protocol. November 1, 2012 (https://www.sprinttrial.org/ public/Protocol_Current.pdf), and also Ambrosius WT, et al. The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: the Systolic Blood Pressure Intervention Trial (SPRINT). Clin Trials 2014; 11: 532-46. ","PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits.","PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits.","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","There were some concerns in one domain."]
["2021/09/21 13.48",42,"JE","SPRINT","SPRINT 2015","Low targets","Standard targets","Doubling of serum creatinine level or 50% reduction in GFR at the end of study","RR=0.90","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","PY","SPRINT will use an internet-based, web browser randomization procedure. ","N","No significant imbalance in the flow chart","Low","Low","SPRINT will use an internet-based, web browser randomization procedure. ",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","Our primary analysis compared the time to the first occurrence of a primary outcome event between the two study groups with the use of the intention-to-treat approach for all randomly assigned participants (NEJM, DOI: 10.1056/NEJMoa1511939).","NA",null,"Some concerns","Some concerns","open trial",null,null,"Y","patients lost to follow-up in study groups were 111/4678 vs 134/4683   (NEJM, DOI: 10.1056/NEJMoa1511939).","NA",null,"NA",null,"NA",null,"Low","Low","No significant differences between groups.",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (NEJM, DOI: 10.1056/NEJMoa1511939, Protocol and Supplementary Appendix). Standing BP will be measured at screening, baseline, 1 month, 6 months, 12 months, and annually thereafter using the same BP device that is used to measure seated BP. After seated determinations, participants will be asked to stand. Beginning when their feet touch the floor, BP will be taken one minute later in the same arm used for the seated measurements, using the BP device. Participants will be asked after the standing determination if they had any symptoms of orthostatic hypotension during the standing BP measurement. The Coordinating Center will calculate BP change using the standing measurements minus the mean of the seated measurements.\n5.3.1 Seated Blood Pressure and Pulse\nSeated blood pressure and pulse are measured at each clinic visit after a rest period using an automated device or manual devises if necessary. The preferred method is the automated device as it offers reduced potential for observer biases and decreased demand on staff in terms of training and effort in data collection.\n5.4.7 Study-related outcomes\nBoth randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3\nmonths for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use\navailable resources and contact information to assess vital status annually on participants not attending study visits.\n","PN","At each quarterly visit, SPRINT staff will specifically query participants for serious adverse events. In addition, information on serious adverse events may also be reported to study staff spontaneously by participants through telephone calls or emails between study visits. In addition to local reporting requirements, all serious adverse events will be recorded by clinic staff and forwarded to the CC Medical Safety Officer within 72 hours of knowledge of the event. SAEs will be collected and reported from screening to the end of the study follow-up period for an individual participant.","NA","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not.","NA",null,"PN",null,"low","low","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not.",null,null,"PY","the design and protocol were published in advance: Systolic Blood Pressure Intervention Trial (SPRINT) protocol. November 1, 2012 (https://www.sprinttrial.org/ public/Protocol_Current.pdf), and also Ambrosius WT, et al. The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: the Systolic Blood Pressure Intervention Trial (SPRINT). Clin Trials 2014; 11: 532-46. ","PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits.","PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits.","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","There were some concerns in one domain."]
["2021/09/21 13.56",43,"JE","SPRINT","SPRINT 2015","Low targets","Standard targets","Proportion of participants reaching target levels of blood pressure at the end of study","RR=0.88","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","PY","SPRINT will use an internet-based, web browser randomization procedure. ","N","No significant imbalance in the flow chart","Low","Low","SPRINT will use an internet-based, web browser randomization procedure. ",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","Our primary analysis compared the time to the first occurrence of a primary outcome event between the two study groups with the use of the intention-to-treat approach for all randomly assigned participants (NEJM, DOI: 10.1056/NEJMoa1511939).","NA",null,"Some concerns","Some concerns","open trial",null,null,"Y","patients lost to follow-up in study groups were 111/4678 vs 134/4683   (NEJM, DOI: 10.1056/NEJMoa1511939).","NA",null,"NA",null,"NA",null,"Low","Low","No significant differences between groups.",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (NEJM, DOI: 10.1056/NEJMoa1511939, Protocol and Supplementary Appendix). Standing BP will be measured at screening, baseline, 1 month, 6 months, 12 months, and annually thereafter using the same BP device that is used to measure seated BP. After seated determinations, participants will be asked to stand. Beginning when their feet touch the floor, BP will be taken one minute later in the same arm used for the seated measurements, using the BP device. Participants will be asked after the standing determination if they had any symptoms of orthostatic hypotension during the standing BP measurement. The Coordinating Center will calculate BP change using the standing measurements minus the mean of the seated measurements.\n5.3.1 Seated Blood Pressure and Pulse\nSeated blood pressure and pulse are measured at each clinic visit after a rest period using an automated device or manual devises if necessary. The preferred method is the automated device as it offers reduced potential for observer biases and decreased demand on staff in terms of training and effort in data collection.\n5.4.7 Study-related outcomes\nBoth randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3\nmonths for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use\navailable resources and contact information to assess vital status annually on participants not attending study visits.\n","PN","At each quarterly visit, SPRINT staff will specifically query participants for serious adverse events. In addition, information on serious adverse events may also be reported to study staff spontaneously by participants through telephone calls or emails between study visits. In addition to local reporting requirements, all serious adverse events will be recorded by clinic staff and forwarded to the CC Medical Safety Officer within 72 hours of knowledge of the event. SAEs will be collected and reported from screening to the end of the study follow-up period for an individual participant.","NA","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not.","NA",null,"PN",null,"low","low","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not.",null,null,"PY","the design and protocol were published in advance: Systolic Blood Pressure Intervention Trial (SPRINT) protocol. November 1, 2012 (https://www.sprinttrial.org/ public/Protocol_Current.pdf), and also Ambrosius WT, et al. The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: the Systolic Blood Pressure Intervention Trial (SPRINT). Clin Trials 2014; 11: 532-46. ","PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits.","PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits.","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","There were some concerns in one domain."]
["2021/09/21 14.06",44,"JE","SPRINT","SPRINT 2015","Low targets","Standard targets","Number of antihypertensive drugs that each participant needed at the end of study","MD=0.91","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","PY","SPRINT will use an internet-based, web browser randomization procedure. ","N","No significant imbalance in the flow chart","Low","Low","SPRINT will use an internet-based, web browser randomization procedure. ",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","Our primary analysis compared the time to the first occurrence of a primary outcome event between the two study groups with the use of the intention-to-treat approach for all randomly assigned participants (NEJM, DOI: 10.1056/NEJMoa1511939).","NA",null,"Some concerns","Some concerns","open trial",null,null,"Y","patients lost to follow-up in study groups were 111/4678 vs 134/4683   (NEJM, DOI: 10.1056/NEJMoa1511939).","NA",null,"NA",null,"NA",null,"Low","Low","No significant differences between groups.",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (NEJM, DOI: 10.1056/NEJMoa1511939, Protocol and Supplementary Appendix). Standing BP will be measured at screening, baseline, 1 month, 6 months, 12 months, and annually thereafter using the same BP device that is used to measure seated BP. After seated determinations, participants will be asked to stand. Beginning when their feet touch the floor, BP will be taken one minute later in the same arm used for the seated measurements, using the BP device. Participants will be asked after the standing determination if they had any symptoms of orthostatic hypotension during the standing BP measurement. The Coordinating Center will calculate BP change using the standing measurements minus the mean of the seated measurements.\n5.3.1 Seated Blood Pressure and Pulse\nSeated blood pressure and pulse are measured at each clinic visit after a rest period using an automated device or manual devises if necessary. The preferred method is the automated device as it offers reduced potential for observer biases and decreased demand on staff in terms of training and effort in data collection.\n5.4.7 Study-related outcomes\nBoth randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3\nmonths for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use\navailable resources and contact information to assess vital status annually on participants not attending study visits.\n","PN","At each quarterly visit, SPRINT staff will specifically query participants for serious adverse events. In addition, information on serious adverse events may also be reported to study staff spontaneously by participants through telephone calls or emails between study visits. In addition to local reporting requirements, all serious adverse events will be recorded by clinic staff and forwarded to the CC Medical Safety Officer within 72 hours of knowledge of the event. SAEs will be collected and reported from screening to the end of the study follow-up period for an individual participant.","NA","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not.","NA",null,"PN",null,"low","low","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not.",null,null,"PY","the design and protocol were published in advance: Systolic Blood Pressure Intervention Trial (SPRINT) protocol. November 1, 2012 (https://www.sprinttrial.org/ public/Protocol_Current.pdf), and also Ambrosius WT, et al. The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: the Systolic Blood Pressure Intervention Trial (SPRINT). Clin Trials 2014; 11: 532-46. ","PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits.","PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits.","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","There were some concerns in one domain."]
["2021/09/22 10.07",45,"JE","SPS3","SPS3 2013","Low targets","Standard targets","total mortality","RR=0.96","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","PY","Following establishment of eligibility and obtaining informed consent, the SPS3 physician and research coordinator will complete baseline data forms at time of randomization. All patients will receive a kit of antiplatelet medications (aspirin plus either clopidogrel or placebo) bearing the randomization number, and all patients, regardless of hypertension status and blood pressure measurements will be randomized to one of the two target levels of BP control. Patients will not be randomized until two weeks after the qualifying stroke, thus BP lowering medications will not be adjusted by the SPS3 physician until at least two weeks following the stroke. Randomization will be stratified by hypertension status.","N","The schedule was computer generated with a permuted-block design (variable block size). Treatment assignments were stored electronically on the study servers at the SPS3 statistical centre, University of Alabama at Birmingham, AL, USA, as well as locally for each study site on an SPS3-designated computer. Upon patients’ eligibility being established, study coordinators ransomised patients via their data entry systems.","Low","Low","The schedule was computer generated with a permuted-block design (variable block size). Treatment assignments were stored electronically on the study servers at the SPS3 statistical centre, University of Alabama at Birmingham, AL, USA, as well as locally for each study site on an SPS3-designated computer. Upon patients’ eligibility being established, study coordinators ransomised patients via their data entry systems.",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","All analyses were based on the intention-to-treat principle and were done with SAS (version 9.2) (Lancet 2013; 382: 507–15).","NA",null,"Some concerns","Some concerns","open trial",null,null,"PY","Blood-pressure therapy was permanently discontinued in similar numbers of patients in the higher-target and lower-target groups (258 [17%] vs 240 [16%]). 90 (3%) participants were lost to follow-up and an additional 465 (15%) ended follow-up early for the following reasons: withdrawn consent (n=242), site closure (n=151), physician request (n=12), and other reasons (n=60). (Lancet 2013; 382: 507–15).","NA",null,"NA",null,"NA",null,"Low","Low","No significant differences between groups.",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (Lancet 2013; 382: 507–15, pp 508-9). Baseline hypertensive status was determined by measurement of blood pressure taken at two consecutive visits before randomisation. Patients taking medications to control blood pressure were allowed to continue doing so.\nBlood pressure was measured three times at every visit and the average measurement was used to decide hypertensive status. Patients were classified as being hypertensive if either or both of the following features were noted: average systolic blood pressure 140 mm Hg or higher or diastolic blood pressure 90 mm Hg or higher on two consecutive visits, and confirmed history of hypertension before the index stroke and taking antihypertensive medication at the time of visit. After randomisation, if patients had blood pressures outside the assigned target range, they were initially seen at least monthly for measurement of blood pressure and adjustment of medications. Patients whose blood pressure was in the relevant range for two consecutive visits were seen every 3 months. If at any point during the study a patient’s systolic blood pressure was outside the assigned target range, he or she was asked to return within 1 month.\nAll study sites were provided with automated Colin Press-Mate BP-8800C sphygmomanometers (Colin Medical Instruments, San Antonio, TX, USA).11 Blood pressure management was overseen at each site by a physician with special expertise in blood-pressure control. If systolic blood pressure in patients assigned to the higher-target group (130–149 mm Hg) dropped to below the lower limit of the target range, the protocol required that patients taking antihypertensive medications stop taking them or have the doses reduced, unless prescribed for reasons other than blood pressure control; patients taking no antihypertensive medications continued to be followed up every 3 months. If systolic blood pressure increased to within the target range, patients were managed according to their originally assigned target. If patients or primary-care physicians refused to titrate blood pressure to the assigned target range per protocol, patients were classified as inactive. Patients whose blood pressure could not be kept within the assigned target range for medical reasons or because of intolerable side-effects of antihypertensive drugs after trying different agents were classified as failure to achieve assigned target. All participants were followed up to a\ncommon end-of-study date, irrespective of activity status. \nThe primary and most secondary outcomes are adjudicated centrally by those unaware of treatment assignment.\n","PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee.","PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee.","NA",null,"NA",null,"Low","Low","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee.",null,null,"PY","the protocol was published in advance at “Benavente O. et al. The Secondary Prevention of Small Subcortical Strokes (SPS3) study (Int J Stroke. 2011 April; 6(2): 164–175)”.  ","PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data.","PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data.","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","There were some concerns in one domain."]
["2021/09/22 10.12",46,"JE","SPS3","SPS3 2013","Low targets","Standard targets","total serious adverse events","RR=1.26","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","PY","Following establishment of eligibility and obtaining informed consent, the SPS3 physician and research coordinator will complete baseline data forms at time of randomization. All patients will receive a kit of antiplatelet medications (aspirin plus either clopidogrel or placebo) bearing the randomization number, and all patients, regardless of hypertension status and blood pressure measurements will be randomized to one of the two target levels of BP control. Patients will not be randomized until two weeks after the qualifying stroke, thus BP lowering medications will not be adjusted by the SPS3 physician until at least two weeks following the stroke. Randomization will be stratified by hypertension status.","N","The schedule was computer generated with a permuted-block design (variable block size). Treatment assignments were stored electronically on the study servers at the SPS3 statistical centre, University of Alabama at Birmingham, AL, USA, as well as locally for each study site on an SPS3-designated computer. Upon patients’ eligibility being established, study coordinators ransomised patients via their data entry systems.","Low","Low","The schedule was computer generated with a permuted-block design (variable block size). Treatment assignments were stored electronically on the study servers at the SPS3 statistical centre, University of Alabama at Birmingham, AL, USA, as well as locally for each study site on an SPS3-designated computer. Upon patients’ eligibility being established, study coordinators ransomised patients via their data entry systems.",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","All analyses were based on the intention-to-treat principle and were done with SAS (version 9.2) (Lancet 2013; 382: 507–15).","NA",null,"Some concerns","Some concerns","open trial",null,null,"PY","Blood-pressure therapy was permanently discontinued in similar numbers of patients in the higher-target and lower-target groups (258 [17%] vs 240 [16%]). 90 (3%) participants were lost to follow-up and an additional 465 (15%) ended follow-up early for the following reasons: withdrawn consent (n=242), site closure (n=151), physician request (n=12), and other reasons (n=60). (Lancet 2013; 382: 507–15).","NA",null,"NA",null,"NA",null,"Low","Low","No significant differences between groups.",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (Lancet 2013; 382: 507–15, pp 508-9). Baseline hypertensive status was determined by measurement of blood pressure taken at two consecutive visits before randomisation. Patients taking medications to control blood pressure were allowed to continue doing so.\nBlood pressure was measured three times at every visit and the average measurement was used to decide hypertensive status. Patients were classified as being hypertensive if either or both of the following features were noted: average systolic blood pressure 140 mm Hg or higher or diastolic blood pressure 90 mm Hg or higher on two consecutive visits, and confirmed history of hypertension before the index stroke and taking antihypertensive medication at the time of visit. After randomisation, if patients had blood pressures outside the assigned target range, they were initially seen at least monthly for measurement of blood pressure and adjustment of medications. Patients whose blood pressure was in the relevant range for two consecutive visits were seen every 3 months. If at any point during the study a patient’s systolic blood pressure was outside the assigned target range, he or she was asked to return within 1 month.\nAll study sites were provided with automated Colin Press-Mate BP-8800C sphygmomanometers (Colin Medical Instruments, San Antonio, TX, USA).11 Blood pressure management was overseen at each site by a physician with special expertise in blood-pressure control. If systolic blood pressure in patients assigned to the higher-target group (130–149 mm Hg) dropped to below the lower limit of the target range, the protocol required that patients taking antihypertensive medications stop taking them or have the doses reduced, unless prescribed for reasons other than blood pressure control; patients taking no antihypertensive medications continued to be followed up every 3 months. If systolic blood pressure increased to within the target range, patients were managed according to their originally assigned target. If patients or primary-care physicians refused to titrate blood pressure to the assigned target range per protocol, patients were classified as inactive. Patients whose blood pressure could not be kept within the assigned target range for medical reasons or because of intolerable side-effects of antihypertensive drugs after trying different agents were classified as failure to achieve assigned target. All participants were followed up to a\ncommon end-of-study date, irrespective of activity status. \nThe primary and most secondary outcomes are adjudicated centrally by those unaware of treatment assignment.\n","PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee.","PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee.","NA",null,"NA",null,"Low","Low","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee.",null,null,"PY","the protocol was published in advance at “Benavente O. et al. The Secondary Prevention of Small Subcortical Strokes (SPS3) study (Int J Stroke. 2011 April; 6(2): 164–175)”.  ","PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data.","PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data.","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","There were some concerns in one domain."]
["2021/09/22 10.18",47,"JE","SPS3","SPS3 2013","Low targets","Standard targets","total cardiovascular events","RR=1.34","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","PY","Following establishment of eligibility and obtaining informed consent, the SPS3 physician and research coordinator will complete baseline data forms at time of randomization. All patients will receive a kit of antiplatelet medications (aspirin plus either clopidogrel or placebo) bearing the randomization number, and all patients, regardless of hypertension status and blood pressure measurements will be randomized to one of the two target levels of BP control. Patients will not be randomized until two weeks after the qualifying stroke, thus BP lowering medications will not be adjusted by the SPS3 physician until at least two weeks following the stroke. Randomization will be stratified by hypertension status.","N","The schedule was computer generated with a permuted-block design (variable block size). Treatment assignments were stored electronically on the study servers at the SPS3 statistical centre, University of Alabama at Birmingham, AL, USA, as well as locally for each study site on an SPS3-designated computer. Upon patients’ eligibility being established, study coordinators ransomised patients via their data entry systems.","Low","Low","The schedule was computer generated with a permuted-block design (variable block size). Treatment assignments were stored electronically on the study servers at the SPS3 statistical centre, University of Alabama at Birmingham, AL, USA, as well as locally for each study site on an SPS3-designated computer. Upon patients’ eligibility being established, study coordinators ransomised patients via their data entry systems.",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","All analyses were based on the intention-to-treat principle and were done with SAS (version 9.2) (Lancet 2013; 382: 507–15).","NA",null,"Some concerns","Some concerns","open trial",null,null,"PY","Blood-pressure therapy was permanently discontinued in similar numbers of patients in the higher-target and lower-target groups (258 [17%] vs 240 [16%]). 90 (3%) participants were lost to follow-up and an additional 465 (15%) ended follow-up early for the following reasons: withdrawn consent (n=242), site closure (n=151), physician request (n=12), and other reasons (n=60). (Lancet 2013; 382: 507–15).","NA",null,"NA",null,"NA",null,"Low","Low","No significant differences between groups.",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (Lancet 2013; 382: 507–15, pp 508-9). Baseline hypertensive status was determined by measurement of blood pressure taken at two consecutive visits before randomisation. Patients taking medications to control blood pressure were allowed to continue doing so.\nBlood pressure was measured three times at every visit and the average measurement was used to decide hypertensive status. Patients were classified as being hypertensive if either or both of the following features were noted: average systolic blood pressure 140 mm Hg or higher or diastolic blood pressure 90 mm Hg or higher on two consecutive visits, and confirmed history of hypertension before the index stroke and taking antihypertensive medication at the time of visit. After randomisation, if patients had blood pressures outside the assigned target range, they were initially seen at least monthly for measurement of blood pressure and adjustment of medications. Patients whose blood pressure was in the relevant range for two consecutive visits were seen every 3 months. If at any point during the study a patient’s systolic blood pressure was outside the assigned target range, he or she was asked to return within 1 month.\nAll study sites were provided with automated Colin Press-Mate BP-8800C sphygmomanometers (Colin Medical Instruments, San Antonio, TX, USA).11 Blood pressure management was overseen at each site by a physician with special expertise in blood-pressure control. If systolic blood pressure in patients assigned to the higher-target group (130–149 mm Hg) dropped to below the lower limit of the target range, the protocol required that patients taking antihypertensive medications stop taking them or have the doses reduced, unless prescribed for reasons other than blood pressure control; patients taking no antihypertensive medications continued to be followed up every 3 months. If systolic blood pressure increased to within the target range, patients were managed according to their originally assigned target. If patients or primary-care physicians refused to titrate blood pressure to the assigned target range per protocol, patients were classified as inactive. Patients whose blood pressure could not be kept within the assigned target range for medical reasons or because of intolerable side-effects of antihypertensive drugs after trying different agents were classified as failure to achieve assigned target. All participants were followed up to a\ncommon end-of-study date, irrespective of activity status. \nThe primary and most secondary outcomes are adjudicated centrally by those unaware of treatment assignment.\n","PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee.","PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee.","NA",null,"NA",null,"Low","Low","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee.",null,null,"PY","the protocol was published in advance at “Benavente O. et al. The Secondary Prevention of Small Subcortical Strokes (SPS3) study (Int J Stroke. 2011 April; 6(2): 164–175)”.  ","PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data.","PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data.","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","There were some concerns in one domain."]
["2021/09/22 10.24",48,"JE","SPS3","SPS3 2013","Low targets","Standard targets","cardiovascular mortality","RR=0.87","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","PY","Following establishment of eligibility and obtaining informed consent, the SPS3 physician and research coordinator will complete baseline data forms at time of randomization. All patients will receive a kit of antiplatelet medications (aspirin plus either clopidogrel or placebo) bearing the randomization number, and all patients, regardless of hypertension status and blood pressure measurements will be randomized to one of the two target levels of BP control. Patients will not be randomized until two weeks after the qualifying stroke, thus BP lowering medications will not be adjusted by the SPS3 physician until at least two weeks following the stroke. Randomization will be stratified by hypertension status.","N","The schedule was computer generated with a permuted-block design (variable block size). Treatment assignments were stored electronically on the study servers at the SPS3 statistical centre, University of Alabama at Birmingham, AL, USA, as well as locally for each study site on an SPS3-designated computer. Upon patients’ eligibility being established, study coordinators ransomised patients via their data entry systems.","Low","Low","The schedule was computer generated with a permuted-block design (variable block size). Treatment assignments were stored electronically on the study servers at the SPS3 statistical centre, University of Alabama at Birmingham, AL, USA, as well as locally for each study site on an SPS3-designated computer. Upon patients’ eligibility being established, study coordinators ransomised patients via their data entry systems.",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","All analyses were based on the intention-to-treat principle and were done with SAS (version 9.2) (Lancet 2013; 382: 507–15).","NA",null,"Some concerns","Some concerns","open trial",null,null,"PY","Blood-pressure therapy was permanently discontinued in similar numbers of patients in the higher-target and lower-target groups (258 [17%] vs 240 [16%]). 90 (3%) participants were lost to follow-up and an additional 465 (15%) ended follow-up early for the following reasons: withdrawn consent (n=242), site closure (n=151), physician request (n=12), and other reasons (n=60). (Lancet 2013; 382: 507–15).","NA",null,"NA",null,"NA",null,"Low","Low","No significant differences between groups.",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (Lancet 2013; 382: 507–15, pp 508-9). Baseline hypertensive status was determined by measurement of blood pressure taken at two consecutive visits before randomisation. Patients taking medications to control blood pressure were allowed to continue doing so.\nBlood pressure was measured three times at every visit and the average measurement was used to decide hypertensive status. Patients were classified as being hypertensive if either or both of the following features were noted: average systolic blood pressure 140 mm Hg or higher or diastolic blood pressure 90 mm Hg or higher on two consecutive visits, and confirmed history of hypertension before the index stroke and taking antihypertensive medication at the time of visit. After randomisation, if patients had blood pressures outside the assigned target range, they were initially seen at least monthly for measurement of blood pressure and adjustment of medications. Patients whose blood pressure was in the relevant range for two consecutive visits were seen every 3 months. If at any point during the study a patient’s systolic blood pressure was outside the assigned target range, he or she was asked to return within 1 month.\nAll study sites were provided with automated Colin Press-Mate BP-8800C sphygmomanometers (Colin Medical Instruments, San Antonio, TX, USA).11 Blood pressure management was overseen at each site by a physician with special expertise in blood-pressure control. If systolic blood pressure in patients assigned to the higher-target group (130–149 mm Hg) dropped to below the lower limit of the target range, the protocol required that patients taking antihypertensive medications stop taking them or have the doses reduced, unless prescribed for reasons other than blood pressure control; patients taking no antihypertensive medications continued to be followed up every 3 months. If systolic blood pressure increased to within the target range, patients were managed according to their originally assigned target. If patients or primary-care physicians refused to titrate blood pressure to the assigned target range per protocol, patients were classified as inactive. Patients whose blood pressure could not be kept within the assigned target range for medical reasons or because of intolerable side-effects of antihypertensive drugs after trying different agents were classified as failure to achieve assigned target. All participants were followed up to a\ncommon end-of-study date, irrespective of activity status. \nThe primary and most secondary outcomes are adjudicated centrally by those unaware of treatment assignment.\n","PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee.","PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee.","NA",null,"NA",null,"Low","Low","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee.",null,null,"PY","the protocol was published in advance at “Benavente O. et al. The Secondary Prevention of Small Subcortical Strokes (SPS3) study (Int J Stroke. 2011 April; 6(2): 164–175)”.  ","PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data.","PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data.","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","There were some concerns in one domain."]
[]
[]
["2021/09/22 10.46",51,"JE","SPS3","SPS3 2013","Low targets","Standard targets","Systolic blood pressure difference from baseline at one year","MD=8.00","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","PY","Following establishment of eligibility and obtaining informed consent, the SPS3 physician and research coordinator will complete baseline data forms at time of randomization. All patients will receive a kit of antiplatelet medications (aspirin plus either clopidogrel or placebo) bearing the randomization number, and all patients, regardless of hypertension status and blood pressure measurements will be randomized to one of the two target levels of BP control. Patients will not be randomized until two weeks after the qualifying stroke, thus BP lowering medications will not be adjusted by the SPS3 physician until at least two weeks following the stroke. Randomization will be stratified by hypertension status.","N","The schedule was computer generated with a permuted-block design (variable block size). Treatment assignments were stored electronically on the study servers at the SPS3 statistical centre, University of Alabama at Birmingham, AL, USA, as well as locally for each study site on an SPS3-designated computer. Upon patients’ eligibility being established, study coordinators ransomised patients via their data entry systems.","Low","Low","The schedule was computer generated with a permuted-block design (variable block size). Treatment assignments were stored electronically on the study servers at the SPS3 statistical centre, University of Alabama at Birmingham, AL, USA, as well as locally for each study site on an SPS3-designated computer. Upon patients’ eligibility being established, study coordinators ransomised patients via their data entry systems.",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","All analyses were based on the intention-to-treat principle and were done with SAS (version 9.2) (Lancet 2013; 382: 507–15).","NA",null,"Some concerns","Some concerns","open trial",null,null,"PY","Blood-pressure therapy was permanently discontinued in similar numbers of patients in the higher-target and lower-target groups (258 [17%] vs 240 [16%]). 90 (3%) participants were lost to follow-up and an additional 465 (15%) ended follow-up early for the following reasons: withdrawn consent (n=242), site closure (n=151), physician request (n=12), and other reasons (n=60). (Lancet 2013; 382: 507–15).","NA",null,"NA",null,"NA",null,"Low","Low","No significant differences between groups.",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (Lancet 2013; 382: 507–15, pp 508-9). Baseline hypertensive status was determined by measurement of blood pressure taken at two consecutive visits before randomisation. Patients taking medications to control blood pressure were allowed to continue doing so.\nBlood pressure was measured three times at every visit and the average measurement was used to decide hypertensive status. Patients were classified as being hypertensive if either or both of the following features were noted: average systolic blood pressure 140 mm Hg or higher or diastolic blood pressure 90 mm Hg or higher on two consecutive visits, and confirmed history of hypertension before the index stroke and taking antihypertensive medication at the time of visit. After randomisation, if patients had blood pressures outside the assigned target range, they were initially seen at least monthly for measurement of blood pressure and adjustment of medications. Patients whose blood pressure was in the relevant range for two consecutive visits were seen every 3 months. If at any point during the study a patient’s systolic blood pressure was outside the assigned target range, he or she was asked to return within 1 month.\nAll study sites were provided with automated Colin Press-Mate BP-8800C sphygmomanometers (Colin Medical Instruments, San Antonio, TX, USA).11 Blood pressure management was overseen at each site by a physician with special expertise in blood-pressure control. If systolic blood pressure in patients assigned to the higher-target group (130–149 mm Hg) dropped to below the lower limit of the target range, the protocol required that patients taking antihypertensive medications stop taking them or have the doses reduced, unless prescribed for reasons other than blood pressure control; patients taking no antihypertensive medications continued to be followed up every 3 months. If systolic blood pressure increased to within the target range, patients were managed according to their originally assigned target. If patients or primary-care physicians refused to titrate blood pressure to the assigned target range per protocol, patients were classified as inactive. Patients whose blood pressure could not be kept within the assigned target range for medical reasons or because of intolerable side-effects of antihypertensive drugs after trying different agents were classified as failure to achieve assigned target. All participants were followed up to a\ncommon end-of-study date, irrespective of activity status. \nThe primary and most secondary outcomes are adjudicated centrally by those unaware of treatment assignment.\n","PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee.","PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee.","NA",null,"NA",null,"Low","Low","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee.",null,null,"PY","the protocol was published in advance at “Benavente O. et al. The Secondary Prevention of Small Subcortical Strokes (SPS3) study (Int J Stroke. 2011 April; 6(2): 164–175)”.  ","PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data.","PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data.","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","There were some concerns in one domain."]
["2021/09/22 10.52",52,"JE","SPS3","SPS3 2013","Low targets","Standard targets","Diastolic blood pressure difference from baseline at one year","MD=4.30","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","PY","Following establishment of eligibility and obtaining informed consent, the SPS3 physician and research coordinator will complete baseline data forms at time of randomization. All patients will receive a kit of antiplatelet medications (aspirin plus either clopidogrel or placebo) bearing the randomization number, and all patients, regardless of hypertension status and blood pressure measurements will be randomized to one of the two target levels of BP control. Patients will not be randomized until two weeks after the qualifying stroke, thus BP lowering medications will not be adjusted by the SPS3 physician until at least two weeks following the stroke. Randomization will be stratified by hypertension status.","N","The schedule was computer generated with a permuted-block design (variable block size). Treatment assignments were stored electronically on the study servers at the SPS3 statistical centre, University of Alabama at Birmingham, AL, USA, as well as locally for each study site on an SPS3-designated computer. Upon patients’ eligibility being established, study coordinators ransomised patients via their data entry systems.","Low","Low","The schedule was computer generated with a permuted-block design (variable block size). Treatment assignments were stored electronically on the study servers at the SPS3 statistical centre, University of Alabama at Birmingham, AL, USA, as well as locally for each study site on an SPS3-designated computer. Upon patients’ eligibility being established, study coordinators ransomised patients via their data entry systems.",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","All analyses were based on the intention-to-treat principle and were done with SAS (version 9.2) (Lancet 2013; 382: 507–15).","NA",null,"Some concerns","Some concerns","open trial",null,null,"PY","Blood-pressure therapy was permanently discontinued in similar numbers of patients in the higher-target and lower-target groups (258 [17%] vs 240 [16%]). 90 (3%) participants were lost to follow-up and an additional 465 (15%) ended follow-up early for the following reasons: withdrawn consent (n=242), site closure (n=151), physician request (n=12), and other reasons (n=60). (Lancet 2013; 382: 507–15).","NA",null,"NA",null,"NA",null,"Low","Low","No significant differences between groups.",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (Lancet 2013; 382: 507–15, pp 508-9). Baseline hypertensive status was determined by measurement of blood pressure taken at two consecutive visits before randomisation. Patients taking medications to control blood pressure were allowed to continue doing so.\nBlood pressure was measured three times at every visit and the average measurement was used to decide hypertensive status. Patients were classified as being hypertensive if either or both of the following features were noted: average systolic blood pressure 140 mm Hg or higher or diastolic blood pressure 90 mm Hg or higher on two consecutive visits, and confirmed history of hypertension before the index stroke and taking antihypertensive medication at the time of visit. After randomisation, if patients had blood pressures outside the assigned target range, they were initially seen at least monthly for measurement of blood pressure and adjustment of medications. Patients whose blood pressure was in the relevant range for two consecutive visits were seen every 3 months. If at any point during the study a patient’s systolic blood pressure was outside the assigned target range, he or she was asked to return within 1 month.\nAll study sites were provided with automated Colin Press-Mate BP-8800C sphygmomanometers (Colin Medical Instruments, San Antonio, TX, USA).11 Blood pressure management was overseen at each site by a physician with special expertise in blood-pressure control. If systolic blood pressure in patients assigned to the higher-target group (130–149 mm Hg) dropped to below the lower limit of the target range, the protocol required that patients taking antihypertensive medications stop taking them or have the doses reduced, unless prescribed for reasons other than blood pressure control; patients taking no antihypertensive medications continued to be followed up every 3 months. If systolic blood pressure increased to within the target range, patients were managed according to their originally assigned target. If patients or primary-care physicians refused to titrate blood pressure to the assigned target range per protocol, patients were classified as inactive. Patients whose blood pressure could not be kept within the assigned target range for medical reasons or because of intolerable side-effects of antihypertensive drugs after trying different agents were classified as failure to achieve assigned target. All participants were followed up to a\ncommon end-of-study date, irrespective of activity status. \nThe primary and most secondary outcomes are adjudicated centrally by those unaware of treatment assignment.\n","PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee.","PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee.","NA",null,"NA",null,"Low","Low","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee.",null,null,"PY","the protocol was published in advance at “Benavente O. et al. The Secondary Prevention of Small Subcortical Strokes (SPS3) study (Int J Stroke. 2011 April; 6(2): 164–175)”.  ","PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data.","PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data.","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","There were some concerns in one domain."]
[]
["2021/09/22 11.15",54,"JE","SPS3","SPS3 2013","Low targets","Standard targets","Proportion of participants reaching target levels of blood pressure at the end of study","RR=1.30","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","PY","Following establishment of eligibility and obtaining informed consent, the SPS3 physician and research coordinator will complete baseline data forms at time of randomization. All patients will receive a kit of antiplatelet medications (aspirin plus either clopidogrel or placebo) bearing the randomization number, and all patients, regardless of hypertension status and blood pressure measurements will be randomized to one of the two target levels of BP control. Patients will not be randomized until two weeks after the qualifying stroke, thus BP lowering medications will not be adjusted by the SPS3 physician until at least two weeks following the stroke. Randomization will be stratified by hypertension status.","N","The schedule was computer generated with a permuted-block design (variable block size). Treatment assignments were stored electronically on the study servers at the SPS3 statistical centre, University of Alabama at Birmingham, AL, USA, as well as locally for each study site on an SPS3-designated computer. Upon patients’ eligibility being established, study coordinators ransomised patients via their data entry systems.","Low","Low","The schedule was computer generated with a permuted-block design (variable block size). Treatment assignments were stored electronically on the study servers at the SPS3 statistical centre, University of Alabama at Birmingham, AL, USA, as well as locally for each study site on an SPS3-designated computer. Upon patients’ eligibility being established, study coordinators ransomised patients via their data entry systems.",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","All analyses were based on the intention-to-treat principle and were done with SAS (version 9.2) (Lancet 2013; 382: 507–15).","NA",null,"Some concerns","Some concerns","open trial",null,null,"PY","Blood-pressure therapy was permanently discontinued in similar numbers of patients in the higher-target and lower-target groups (258 [17%] vs 240 [16%]). 90 (3%) participants were lost to follow-up and an additional 465 (15%) ended follow-up early for the following reasons: withdrawn consent (n=242), site closure (n=151), physician request (n=12), and other reasons (n=60). (Lancet 2013; 382: 507–15).","NA",null,"NA",null,"NA",null,"Low","Low","No significant differences between groups.",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (Lancet 2013; 382: 507–15, pp 508-9). Baseline hypertensive status was determined by measurement of blood pressure taken at two consecutive visits before randomisation. Patients taking medications to control blood pressure were allowed to continue doing so.\nBlood pressure was measured three times at every visit and the average measurement was used to decide hypertensive status. Patients were classified as being hypertensive if either or both of the following features were noted: average systolic blood pressure 140 mm Hg or higher or diastolic blood pressure 90 mm Hg or higher on two consecutive visits, and confirmed history of hypertension before the index stroke and taking antihypertensive medication at the time of visit. After randomisation, if patients had blood pressures outside the assigned target range, they were initially seen at least monthly for measurement of blood pressure and adjustment of medications. Patients whose blood pressure was in the relevant range for two consecutive visits were seen every 3 months. If at any point during the study a patient’s systolic blood pressure was outside the assigned target range, he or she was asked to return within 1 month.\nAll study sites were provided with automated Colin Press-Mate BP-8800C sphygmomanometers (Colin Medical Instruments, San Antonio, TX, USA).11 Blood pressure management was overseen at each site by a physician with special expertise in blood-pressure control. If systolic blood pressure in patients assigned to the higher-target group (130–149 mm Hg) dropped to below the lower limit of the target range, the protocol required that patients taking antihypertensive medications stop taking them or have the doses reduced, unless prescribed for reasons other than blood pressure control; patients taking no antihypertensive medications continued to be followed up every 3 months. If systolic blood pressure increased to within the target range, patients were managed according to their originally assigned target. If patients or primary-care physicians refused to titrate blood pressure to the assigned target range per protocol, patients were classified as inactive. Patients whose blood pressure could not be kept within the assigned target range for medical reasons or because of intolerable side-effects of antihypertensive drugs after trying different agents were classified as failure to achieve assigned target. All participants were followed up to a\ncommon end-of-study date, irrespective of activity status. \nThe primary and most secondary outcomes are adjudicated centrally by those unaware of treatment assignment.\n","PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee.","PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee.","NA",null,"NA",null,"Low","Low","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee.",null,null,"PY","the protocol was published in advance at “Benavente O. et al. The Secondary Prevention of Small Subcortical Strokes (SPS3) study (Int J Stroke. 2011 April; 6(2): 164–175)”.  ","PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data.","PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data.","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","There were some concerns in one domain."]
["2021/09/22 11.26",55,"JE","SPS3","SPS3 2013","Low targets","Standard targets","Number of antihypertensive drugs that each participant needed at the end of study","MD=0.50","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","PY","Following establishment of eligibility and obtaining informed consent, the SPS3 physician and research coordinator will complete baseline data forms at time of randomization. All patients will receive a kit of antiplatelet medications (aspirin plus either clopidogrel or placebo) bearing the randomization number, and all patients, regardless of hypertension status and blood pressure measurements will be randomized to one of the two target levels of BP control. Patients will not be randomized until two weeks after the qualifying stroke, thus BP lowering medications will not be adjusted by the SPS3 physician until at least two weeks following the stroke. Randomization will be stratified by hypertension status.","N","The schedule was computer generated with a permuted-block design (variable block size). Treatment assignments were stored electronically on the study servers at the SPS3 statistical centre, University of Alabama at Birmingham, AL, USA, as well as locally for each study site on an SPS3-designated computer. Upon patients’ eligibility being established, study coordinators ransomised patients via their data entry systems.","Low","Low","The schedule was computer generated with a permuted-block design (variable block size). Treatment assignments were stored electronically on the study servers at the SPS3 statistical centre, University of Alabama at Birmingham, AL, USA, as well as locally for each study site on an SPS3-designated computer. Upon patients’ eligibility being established, study coordinators ransomised patients via their data entry systems.",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","All analyses were based on the intention-to-treat principle and were done with SAS (version 9.2) (Lancet 2013; 382: 507–15).","NA",null,"Some concerns","Some concerns","open trial",null,null,"PY","Blood-pressure therapy was permanently discontinued in similar numbers of patients in the higher-target and lower-target groups (258 [17%] vs 240 [16%]). 90 (3%) participants were lost to follow-up and an additional 465 (15%) ended follow-up early for the following reasons: withdrawn consent (n=242), site closure (n=151), physician request (n=12), and other reasons (n=60). (Lancet 2013; 382: 507–15).","NA",null,"NA",null,"NA",null,"Low","Low","No significant differences between groups.",null,null,"N","blood pressure measurement is correct and outcomes are determined according to standard methods (Lancet 2013; 382: 507–15, pp 508-9). Baseline hypertensive status was determined by measurement of blood pressure taken at two consecutive visits before randomisation. Patients taking medications to control blood pressure were allowed to continue doing so.\nBlood pressure was measured three times at every visit and the average measurement was used to decide hypertensive status. Patients were classified as being hypertensive if either or both of the following features were noted: average systolic blood pressure 140 mm Hg or higher or diastolic blood pressure 90 mm Hg or higher on two consecutive visits, and confirmed history of hypertension before the index stroke and taking antihypertensive medication at the time of visit. After randomisation, if patients had blood pressures outside the assigned target range, they were initially seen at least monthly for measurement of blood pressure and adjustment of medications. Patients whose blood pressure was in the relevant range for two consecutive visits were seen every 3 months. If at any point during the study a patient’s systolic blood pressure was outside the assigned target range, he or she was asked to return within 1 month.\nAll study sites were provided with automated Colin Press-Mate BP-8800C sphygmomanometers (Colin Medical Instruments, San Antonio, TX, USA).11 Blood pressure management was overseen at each site by a physician with special expertise in blood-pressure control. If systolic blood pressure in patients assigned to the higher-target group (130–149 mm Hg) dropped to below the lower limit of the target range, the protocol required that patients taking antihypertensive medications stop taking them or have the doses reduced, unless prescribed for reasons other than blood pressure control; patients taking no antihypertensive medications continued to be followed up every 3 months. If systolic blood pressure increased to within the target range, patients were managed according to their originally assigned target. If patients or primary-care physicians refused to titrate blood pressure to the assigned target range per protocol, patients were classified as inactive. Patients whose blood pressure could not be kept within the assigned target range for medical reasons or because of intolerable side-effects of antihypertensive drugs after trying different agents were classified as failure to achieve assigned target. All participants were followed up to a\ncommon end-of-study date, irrespective of activity status. \nThe primary and most secondary outcomes are adjudicated centrally by those unaware of treatment assignment.\n","PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee.","PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee.","NA",null,"NA",null,"Low","Low","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee.",null,null,"PY","the protocol was published in advance at “Benavente O. et al. The Secondary Prevention of Small Subcortical Strokes (SPS3) study (Int J Stroke. 2011 April; 6(2): 164–175)”.  ","PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data.","PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data.","Low","Low","individual-patient data available",null,null,"Some concerns","Some concerns","There were some concerns in one domain."]
["2021/10/25 14.51",56,"JE","MDRD","MDRD 1994","Low targets","Standard targets","total mortality","RR=1.35","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","Y","The randomization schedules will be prepared by the Data Coordinating Center prior to the start of patient recruitment. Allocation to treatment groups will be equal. The specific allocation procedure will be a stratified block randomization procedure. The size of each block will be determined in a random fashion. The randomization process will be centrally administered. All randomization schedules will remain confidential and known only by members of the Data Coordinating Center staff. ","N",null,"Low","Low","The randomization schedules will be prepared by the Data Coordinating Center prior to the start of patient recruitment. Allocation to treatment groups will be equal. The specific allocation procedure will be a stratified block randomization procedure. The size of each block will be determined in a random fashion. The randomization process will be centrally administered. All randomization schedules will remain confidential and known only by members of the Data Coordinating Center staff. ",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","Using an intention-to-treat analysis, we related follow-up measurements of the patients’ glomerular filtration rates to the prescribed interventions (NEJM 1994;330:877-84).","NA",null,"Some concerns","Some concerns","open trial",null,null,"PY","Eleven of the 585 patients in study 1 (1.9 percent) and 3 of the 255 in study 2 (1.2 percent) were lost to follow-up. (NEJM 1994;330:877-84).","N",null,"NA",null,"PN",null,"Low","Low","Eleven of the 585 patients in study 1 (1.9 percent) and 3 of the 255 in study 2 (1.2 percent) were lost to follow-up.",null,null,"PN","blood pressure measurement is correct and outcomes are determined according to standard methods (Design and Statistical Issues of the Modification of Diet in Renal Disease Trial. Controlled Clinical Trials 12:566-586 (1991)). Treatment strategies to achieve these goals follow the recommendations of the Joint National Commission on Detection, Evaluation, and Treatment of High Blood Pressure. Blood pressure is measured in the right arm after 5 minutes rest with a random-zero sphygmomanometer. Three consecutive readings are obtained with the patient sitting. The average of the last two measurements is taken as the visit blood pressure.\nA quality control program for each measurement and procedure was implemented and assessed in each clinical center and central facility. Quality control data were reviewed regularly by the Quality Control Committee and by the External Monitoring Committee and found to be acceptable.\n","PN","Follow-up Procedures and Measurements. Protein intake was assessed monthly on the basis of 24-hour urinary excretion of urea nitrogen. Nitrogen in the prescribed keto acid-amino acid supplement was subtracted from urinary urea nitrogen. The intake of protein, calories, and other nutrients was assessed every two months on the basis of three-day dietary records. Blood pressure was measured monthly, and when necessary, adjustments in therapy were made monthly or more often. The glomerular filtration rate was measured at two months, at four months, and every four months thereafter on the basis of the renal clearance of [125I) iothalamate (Isotex Diagnostics, Friendswood, Tex.). Anthropometric measurements were obtained every four months.","NI",null,"NI",null,"NI",null,"High","High","Blood pressure was measured monthly, and when necessary, adjustments in therapy were made monthly or more often. No information is provoded for Q4.2 and Q4.3",null,null,"PY","the protocol was published in advance at “Design and Statistical Issues of the Modification of Diet in Renal Disease Trial. Controlled Clinical Trials 12:566-586 (1991)” and “The Modification of Diet in Renal Disease Study: Design, Methods, and Results From the Feasibility Study. American Journal of Kidney Diseases, Vol XX, No 1 (July), 1992: pp 18-33”.","PN","The database shows all required results.","PN","Protocol and main article checked","Low","Low","The database shows all required results.",null,null,"High","High ","There is some concern in one domain and high concern in another one."]
["2021/10/25 14.53",57,"JE","MDRD","MDRD 1994","Low targets","Standard targets","total serious adverse events","RR=1.12","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","Y","The randomization schedules will be prepared by the Data Coordinating Center prior to the start of patient recruitment. Allocation to treatment groups will be equal. The specific allocation procedure will be a stratified block randomization procedure. The size of each block will be determined in a random fashion. The randomization process will be centrally administered. All randomization schedules will remain confidential and known only by members of the Data Coordinating Center staff. ","N",null,"Low","Low","The randomization schedules will be prepared by the Data Coordinating Center prior to the start of patient recruitment. Allocation to treatment groups will be equal. The specific allocation procedure will be a stratified block randomization procedure. The size of each block will be determined in a random fashion. The randomization process will be centrally administered. All randomization schedules will remain confidential and known only by members of the Data Coordinating Center staff. ",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","Using an intention-to-treat analysis, we related follow-up measurements of the patients’ glomerular filtration rates to the prescribed interventions (NEJM 1994;330:877-84).","NA",null,"Some concerns","Some concerns","open trial",null,null,"PY","Eleven of the 585 patients in study 1 (1.9 percent) and 3 of the 255 in study 2 (1.2 percent) were lost to follow-up. (NEJM 1994;330:877-84).","N",null,"NA",null,"PN",null,"Low","Low","Eleven of the 585 patients in study 1 (1.9 percent) and 3 of the 255 in study 2 (1.2 percent) were lost to follow-up.",null,null,"PN","blood pressure measurement is correct and outcomes are determined according to standard methods (Design and Statistical Issues of the Modification of Diet in Renal Disease Trial. Controlled Clinical Trials 12:566-586 (1991)). Treatment strategies to achieve these goals follow the recommendations of the Joint National Commission on Detection, Evaluation, and Treatment of High Blood Pressure. Blood pressure is measured in the right arm after 5 minutes rest with a random-zero sphygmomanometer. Three consecutive readings are obtained with the patient sitting. The average of the last two measurements is taken as the visit blood pressure.\nA quality control program for each measurement and procedure was implemented and assessed in each clinical center and central facility. Quality control data were reviewed regularly by the Quality Control Committee and by the External Monitoring Committee and found to be acceptable.\n","PN","Follow-up Procedures and Measurements. Protein intake was assessed monthly on the basis of 24-hour urinary excretion of urea nitrogen. Nitrogen in the prescribed keto acid-amino acid supplement was subtracted from urinary urea nitrogen. The intake of protein, calories, and other nutrients was assessed every two months on the basis of three-day dietary records. Blood pressure was measured monthly, and when necessary, adjustments in therapy were made monthly or more often. The glomerular filtration rate was measured at two months, at four months, and every four months thereafter on the basis of the renal clearance of [125I) iothalamate (Isotex Diagnostics, Friendswood, Tex.). Anthropometric measurements were obtained every four months.","NI",null,"NI",null,"NI",null,"High","High ","Blood pressure was measured monthly, and when necessary, adjustments in therapy were made monthly or more often. No information is provoded for Q4.2 and Q4.4",null,null,"PY","the protocol was published in advance at “Design and Statistical Issues of the Modification of Diet in Renal Disease Trial. Controlled Clinical Trials 12:566-586 (1991)” and “The Modification of Diet in Renal Disease Study: Design, Methods, and Results From the Feasibility Study. American Journal of Kidney Diseases, Vol XX, No 1 (July), 1992: pp 18-33”.","PN","The database shows all required results","PN","Protocol and main article checked","Low","Low","The database shows all required results.",null,null,"High","High ","There is some concern in one domain and high concern in another one."]
[]
["2021/10/26 11.47",59,"JE","MDRD","MDRD 1994","Low targets","Standard targets","cardiovascular mortality","RR=1.42","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","Y","The randomization schedules will be prepared by the Data Coordinating Center prior to the start of patient recruitment. Allocation to treatment groups will be equal. The specific allocation procedure will be a stratified block randomization procedure. The size of each block will be determined in a random fashion. The randomization process will be centrally administered. All randomization schedules will remain confidential and known only by members of the Data Coordinating Center staff. ","N",null,"Low","Low","The randomization schedules will be prepared by the Data Coordinating Center prior to the start of patient recruitment. Allocation to treatment groups will be equal. The specific allocation procedure will be a stratified block randomization procedure. The size of each block will be determined in a random fashion. The randomization process will be centrally administered. All randomization schedules will remain confidential and known only by members of the Data Coordinating Center staff. ",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","Using an intention-to-treat analysis, we related follow-up measurements of the patients’ glomerular filtration rates to the prescribed interventions (NEJM 1994;330:877-84).","NA",null,"Some concerns","Some concerns","open trial",null,null,"PY","Eleven of the 585 patients in study 1 (1.9 percent) and 3 of the 255 in study 2 (1.2 percent) were lost to follow-up. (NEJM 1994;330:877-84).","N",null,"NA",null,"PN",null,"Low","Low","Eleven of the 585 patients in study 1 (1.9 percent) and 3 of the 255 in study 2 (1.2 percent) were lost to follow-up.",null,null,"PN","blood pressure measurement is correct and outcomes are determined according to standard methods (Design and Statistical Issues of the Modification of Diet in Renal Disease Trial. Controlled Clinical Trials 12:566-586 (1991)). Treatment strategies to achieve these goals follow the recommendations of the Joint National Commission on Detection, Evaluation, and Treatment of High Blood Pressure. Blood pressure is measured in the right arm after 5 minutes rest with a random-zero sphygmomanometer. Three consecutive readings are obtained with the patient sitting. The average of the last two measurements is taken as the visit blood pressure.\nA quality control program for each measurement and procedure was implemented and assessed in each clinical center and central facility. Quality control data were reviewed regularly by the Quality Control Committee and by the External Monitoring Committee and found to be acceptable.\n","PN","Follow-up Procedures and Measurements. Protein intake was assessed monthly on the basis of 24-hour urinary excretion of urea nitrogen. Nitrogen in the prescribed keto acid-amino acid supplement was subtracted from urinary urea nitrogen. The intake of protein, calories, and other nutrients was assessed every two months on the basis of three-day dietary records. Blood pressure was measured monthly, and when necessary, adjustments in therapy were made monthly or more often. The glomerular filtration rate was measured at two months, at four months, and every four months thereafter on the basis of the renal clearance of [125I) iothalamate (Isotex Diagnostics, Friendswood, Tex.). Anthropometric measurements were obtained every four months.","NI",null,"NI",null,"NI",null,"High","High ","Blood pressure was measured monthly, and when necessary, adjustments in therapy were made monthly or more often. No information is provoded for Q4.2 and Q4.6",null,null,"PY","the protocol was published in advance at “Design and Statistical Issues of the Modification of Diet in Renal Disease Trial. Controlled Clinical Trials 12:566-586 (1991)” and “The Modification of Diet in Renal Disease Study: Design, Methods, and Results From the Feasibility Study. American Journal of Kidney Diseases, Vol XX, No 1 (July), 1992: pp 18-33”.","PN","The database shows all required results","PN","Protocol and main article checked","Low","Low","The database shows all required results.",null,null,"High ","High ","There is some concern in one domain and high concern in another one."]
["2021/10/25 10.20",60,"JE","MDRD","MDRD 1994","Low targets","Standard targets","kidney failure","RR=0.98","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","Y","The randomization schedules will be prepared by the Data Coordinating Center prior to the start of patient recruitment. Allocation to treatment groups will be equal. The specific allocation procedure will be a stratified block randomization procedure. The size of each block will be determined in a random fashion. The randomization process will be centrally administered. All randomization schedules will remain confidential and known only by members of the Data Coordinating Center staff. ","N",null,"Low","Low","The randomization schedules will be prepared by the Data Coordinating Center prior to the start of patient recruitment. Allocation to treatment groups will be equal. The specific allocation procedure will be a stratified block randomization procedure. The size of each block will be determined in a random fashion. The randomization process will be centrally administered. All randomization schedules will remain confidential and known only by members of the Data Coordinating Center staff. ",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","Using an intention-to-treat analysis, we related follow-up measurements of the patients’ glomerular filtration rates to the prescribed interventions (NEJM 1994;330:877-84).","NA",null,"Some concerns","Some concerns","open trial",null,null,"PY","Eleven of the 585 patients in study 1 (1.9 percent) and 3 of the 255 in study 2 (1.2 percent) were lost to follow-up. (NEJM 1994;330:877-84).","N",null,"NA",null,"PN",null,"Low","Low","Eleven of the 585 patients in study 1 (1.9 percent) and 3 of the 255 in study 2 (1.2 percent) were lost to follow-up.",null,null,"PN","blood pressure measurement is correct and outcomes are determined according to standard methods (Design and Statistical Issues of the Modification of Diet in Renal Disease Trial. Controlled Clinical Trials 12:566-586 (1991)). Treatment strategies to achieve these goals follow the recommendations of the Joint National Commission on Detection, Evaluation, and Treatment of High Blood Pressure. Blood pressure is measured in the right arm after 5 minutes rest with a random-zero sphygmomanometer. Three consecutive readings are obtained with the patient sitting. The average of the last two measurements is taken as the visit blood pressure.\nA quality control program for each measurement and procedure was implemented and assessed in each clinical center and central facility. Quality control data were reviewed regularly by the Quality Control Committee and by the External Monitoring Committee and found to be acceptable.\n","PN","Follow-up Procedures and Measurements. Protein intake was assessed monthly on the basis of 24-hour urinary excretion of urea nitrogen. Nitrogen in the prescribed keto acid-amino acid supplement was subtracted from urinary urea nitrogen. The intake of protein, calories, and other nutrients was assessed every two months on the basis of three-day dietary records. Blood pressure was measured monthly, and when necessary, adjustments in therapy were made monthly or more often. The glomerular filtration rate was measured at two months, at four months, and every four months thereafter on the basis of the renal clearance of [125I) iothalamate (Isotex Diagnostics, Friendswood, Tex.). Anthropometric measurements were obtained every four months.","NA",null,"NA",null,"NA",null,"High ","High ","Blood pressure was measured monthly, and when necessary, adjustments in therapy were made monthly or more often. No information is provoded for Q4.2 and Q4.7",null,null,"PY","the protocol was published in advance at “Design and Statistical Issues of the Modification of Diet in Renal Disease Trial. Controlled Clinical Trials 12:566-586 (1991)” and “The Modification of Diet in Renal Disease Study: Design, Methods, and Results From the Feasibility Study. American Journal of Kidney Diseases, Vol XX, No 1 (July), 1992: pp 18-33”.","PN","The database shows all required results","PN","Protocol and main article checked","Low","Low","The database shows all required results.",null,null,"High ","High ","There is some concern in one domain and high concern in another one."]
[]
["2021/10/26 10.15",62,"JE","MDRD","MDRD 1994","Low targets","Standard targets","Systolic blood pressure difference from baseline at one year","MD=5.30","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","Y","The randomization schedules will be prepared by the Data Coordinating Center prior to the start of patient recruitment. Allocation to treatment groups will be equal. The specific allocation procedure will be a stratified block randomization procedure. The size of each block will be determined in a random fashion. The randomization process will be centrally administered. All randomization schedules will remain confidential and known only by members of the Data Coordinating Center staff. ","N",null,"Low","Low","The randomization schedules will be prepared by the Data Coordinating Center prior to the start of patient recruitment. Allocation to treatment groups will be equal. The specific allocation procedure will be a stratified block randomization procedure. The size of each block will be determined in a random fashion. The randomization process will be centrally administered. All randomization schedules will remain confidential and known only by members of the Data Coordinating Center staff. ",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","Using an intention-to-treat analysis, we related follow-up measurements of the patients’ glomerular filtration rates to the prescribed interventions (NEJM 1994;330:877-84).","NA",null,"Some concerns","Some concerns","open trial",null,null,"PY","Eleven of the 585 patients in study 1 (1.9 percent) and 3 of the 255 in study 2 (1.2 percent) were lost to follow-up. (NEJM 1994;330:877-84).","N",null,"NA",null,"PN",null,"Low","Low","Eleven of the 585 patients in study 1 (1.9 percent) and 3 of the 255 in study 2 (1.2 percent) were lost to follow-up.",null,null,"PN","blood pressure measurement is correct and outcomes are determined according to standard methods (Design and Statistical Issues of the Modification of Diet in Renal Disease Trial. Controlled Clinical Trials 12:566-586 (1991)). Treatment strategies to achieve these goals follow the recommendations of the Joint National Commission on Detection, Evaluation, and Treatment of High Blood Pressure. Blood pressure is measured in the right arm after 5 minutes rest with a random-zero sphygmomanometer. Three consecutive readings are obtained with the patient sitting. The average of the last two measurements is taken as the visit blood pressure.\nA quality control program for each measurement and procedure was implemented and assessed in each clinical center and central facility. Quality control data were reviewed regularly by the Quality Control Committee and by the External Monitoring Committee and found to be acceptable.\n","PN","Follow-up Procedures and Measurements. Protein intake was assessed monthly on the basis of 24-hour urinary excretion of urea nitrogen. Nitrogen in the prescribed keto acid-amino acid supplement was subtracted from urinary urea nitrogen. The intake of protein, calories, and other nutrients was assessed every two months on the basis of three-day dietary records. Blood pressure was measured monthly, and when necessary, adjustments in therapy were made monthly or more often. The glomerular filtration rate was measured at two months, at four months, and every four months thereafter on the basis of the renal clearance of [125I) iothalamate (Isotex Diagnostics, Friendswood, Tex.). Anthropometric measurements were obtained every four months.","NI",null,"NI",null,"NI",null,"High","High ","Blood pressure was measured monthly, and when necessary, adjustments in therapy were made monthly or more often. No information is provoded for Q4.2 and Q4.9",null,null,"PY","the protocol was published in advance at “Design and Statistical Issues of the Modification of Diet in Renal Disease Trial. Controlled Clinical Trials 12:566-586 (1991)” and “The Modification of Diet in Renal Disease Study: Design, Methods, and Results From the Feasibility Study. American Journal of Kidney Diseases, Vol XX, No 1 (July), 1992: pp 18-33”.","PN","The database shows all required results","PN","Protocol and main article checked","Low","Low","The database shows all required results.",null,null,"High ","High","There is some concern in one domain and high concern in another one."]
["2021/10/25 11.08",63,"JE","MDRD","MDRD 1994","Low targets","Standard targets","Diastolic blood pressure difference from baseline at one year","MD=4.00","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","Y","The randomization schedules will be prepared by the Data Coordinating Center prior to the start of patient recruitment. Allocation to treatment groups will be equal. The specific allocation procedure will be a stratified block randomization procedure. The size of each block will be determined in a random fashion. The randomization process will be centrally administered. All randomization schedules will remain confidential and known only by members of the Data Coordinating Center staff. ","N",null,"Low","Low","The randomization schedules will be prepared by the Data Coordinating Center prior to the start of patient recruitment. Allocation to treatment groups will be equal. The specific allocation procedure will be a stratified block randomization procedure. The size of each block will be determined in a random fashion. The randomization process will be centrally administered. All randomization schedules will remain confidential and known only by members of the Data Coordinating Center staff. ",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","Using an intention-to-treat analysis, we related follow-up measurements of the patients’ glomerular filtration rates to the prescribed interventions (NEJM 1994;330:877-84).","NA",null,"Some concerns","Some concerns","open trial",null,null,"PY","Eleven of the 585 patients in study 1 (1.9 percent) and 3 of the 255 in study 2 (1.2 percent) were lost to follow-up. (NEJM 1994;330:877-84).","N",null,"NA",null,"PN",null,"Low","Low","Eleven of the 585 patients in study 1 (1.9 percent) and 3 of the 255 in study 2 (1.2 percent) were lost to follow-up.",null,null,"PN","blood pressure measurement is correct and outcomes are determined according to standard methods (Design and Statistical Issues of the Modification of Diet in Renal Disease Trial. Controlled Clinical Trials 12:566-586 (1991)). Treatment strategies to achieve these goals follow the recommendations of the Joint National Commission on Detection, Evaluation, and Treatment of High Blood Pressure. Blood pressure is measured in the right arm after 5 minutes rest with a random-zero sphygmomanometer. Three consecutive readings are obtained with the patient sitting. The average of the last two measurements is taken as the visit blood pressure.\nA quality control program for each measurement and procedure was implemented and assessed in each clinical center and central facility. Quality control data were reviewed regularly by the Quality Control Committee and by the External Monitoring Committee and found to be acceptable.\n","PN","Follow-up Procedures and Measurements. Protein intake was assessed monthly on the basis of 24-hour urinary excretion of urea nitrogen. Nitrogen in the prescribed keto acid-amino acid supplement was subtracted from urinary urea nitrogen. The intake of protein, calories, and other nutrients was assessed every two months on the basis of three-day dietary records. Blood pressure was measured monthly, and when necessary, adjustments in therapy were made monthly or more often. The glomerular filtration rate was measured at two months, at four months, and every four months thereafter on the basis of the renal clearance of [125I) iothalamate (Isotex Diagnostics, Friendswood, Tex.). Anthropometric measurements were obtained every four months.","NI",null,"NI",null,"NI",null,"High","High ","Blood pressure was measured monthly, and when necessary, adjustments in therapy were made monthly or more often. No information is provoded for Q4.2 and Q4.10",null,null,"PY","the protocol was published in advance at “Design and Statistical Issues of the Modification of Diet in Renal Disease Trial. Controlled Clinical Trials 12:566-586 (1991)” and “The Modification of Diet in Renal Disease Study: Design, Methods, and Results From the Feasibility Study. American Journal of Kidney Diseases, Vol XX, No 1 (July), 1992: pp 18-33”.","PN","The database shows all required results","PN","Protocol and main article checked","Low","Low","The database shows all required results.",null,null,"High ","High ","There is some concern in one domain and high concern in another one."]
["2021/10/25 11.09",64,"JE","MDRD","MDRD 1994","Low targets","Standard targets","Doubling of serum creatinine level or 50% reduction in GFR at the end of study","RR=0.67","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","Y","The randomization schedules will be prepared by the Data Coordinating Center prior to the start of patient recruitment. Allocation to treatment groups will be equal. The specific allocation procedure will be a stratified block randomization procedure. The size of each block will be determined in a random fashion. The randomization process will be centrally administered. All randomization schedules will remain confidential and known only by members of the Data Coordinating Center staff. ","N",null,"Low","Low","The randomization schedules will be prepared by the Data Coordinating Center prior to the start of patient recruitment. Allocation to treatment groups will be equal. The specific allocation procedure will be a stratified block randomization procedure. The size of each block will be determined in a random fashion. The randomization process will be centrally administered. All randomization schedules will remain confidential and known only by members of the Data Coordinating Center staff. ",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","Using an intention-to-treat analysis, we related follow-up measurements of the patients’ glomerular filtration rates to the prescribed interventions (NEJM 1994;330:877-84).","NA",null,"Some concerns","Some concerns","open trial",null,null,"PY","Eleven of the 585 patients in study 1 (1.9 percent) and 3 of the 255 in study 2 (1.2 percent) were lost to follow-up. (NEJM 1994;330:877-84).","N",null,"NA",null,"PN",null,"Low","Low","Eleven of the 585 patients in study 1 (1.9 percent) and 3 of the 255 in study 2 (1.2 percent) were lost to follow-up.",null,null,"PN","blood pressure measurement is correct and outcomes are determined according to standard methods (Design and Statistical Issues of the Modification of Diet in Renal Disease Trial. Controlled Clinical Trials 12:566-586 (1991)). Treatment strategies to achieve these goals follow the recommendations of the Joint National Commission on Detection, Evaluation, and Treatment of High Blood Pressure. Blood pressure is measured in the right arm after 5 minutes rest with a random-zero sphygmomanometer. Three consecutive readings are obtained with the patient sitting. The average of the last two measurements is taken as the visit blood pressure.\nA quality control program for each measurement and procedure was implemented and assessed in each clinical center and central facility. Quality control data were reviewed regularly by the Quality Control Committee and by the External Monitoring Committee and found to be acceptable.\n","PN","Follow-up Procedures and Measurements. Protein intake was assessed monthly on the basis of 24-hour urinary excretion of urea nitrogen. Nitrogen in the prescribed keto acid-amino acid supplement was subtracted from urinary urea nitrogen. The intake of protein, calories, and other nutrients was assessed every two months on the basis of three-day dietary records. Blood pressure was measured monthly, and when necessary, adjustments in therapy were made monthly or more often. The glomerular filtration rate was measured at two months, at four months, and every four months thereafter on the basis of the renal clearance of [125I) iothalamate (Isotex Diagnostics, Friendswood, Tex.). Anthropometric measurements were obtained every four months.","NI",null,"NI",null,"NI",null,"High","High ","Blood pressure was measured monthly, and when necessary, adjustments in therapy were made monthly or more often. No information is provoded for Q4.2 and Q4.11",null,null,"PY","the protocol was published in advance at “Design and Statistical Issues of the Modification of Diet in Renal Disease Trial. Controlled Clinical Trials 12:566-586 (1991)” and “The Modification of Diet in Renal Disease Study: Design, Methods, and Results From the Feasibility Study. American Journal of Kidney Diseases, Vol XX, No 1 (July), 1992: pp 18-33”.","PN","The database shows all required results","PN","Protocol and main article checked","Low","Low","The database shows all required results.",null,null,"High ","High ","There is some concern in one domain and high concern in another one."]
["2021/10/25 11.09",65,"JE","MDRD","MDRD 1994","Low targets","Standard targets","Proportion of participants reaching target levels of blood pressure at the end of study","RR=0.65","assignment to intervention (the 'intention-to-treat' effect)","NA",1," Journal article(s); Trial protocol","Y","Y","The randomization schedules will be prepared by the Data Coordinating Center prior to the start of patient recruitment. Allocation to treatment groups will be equal. The specific allocation procedure will be a stratified block randomization procedure. The size of each block will be determined in a random fashion. The randomization process will be centrally administered. All randomization schedules will remain confidential and known only by members of the Data Coordinating Center staff. ","N",null,"Low","Low","The randomization schedules will be prepared by the Data Coordinating Center prior to the start of patient recruitment. Allocation to treatment groups will be equal. The specific allocation procedure will be a stratified block randomization procedure. The size of each block will be determined in a random fashion. The randomization process will be centrally administered. All randomization schedules will remain confidential and known only by members of the Data Coordinating Center staff. ",null,null,"Y","Y","open trial","NI",null,"NA",null,"NA",null,"Y","Using an intention-to-treat analysis, we related follow-up measurements of the patients’ glomerular filtration rates to the prescribed interventions (NEJM 1994;330:877-84).","NA",null,"Some concerns","Some concerns","open trial",null,null,"PY","Eleven of the 585 patients in study 1 (1.9 percent) and 3 of the 255 in study 2 (1.2 percent) were lost to follow-up. (NEJM 1994;330:877-84).","N",null,"NA",null,"PN",null,"Low","Low","Eleven of the 585 patients in study 1 (1.9 percent) and 3 of the 255 in study 2 (1.2 percent) were lost to follow-up.",null,null,"PN","blood pressure measurement is correct and outcomes are determined according to standard methods (Design and Statistical Issues of the Modification of Diet in Renal Disease Trial. Controlled Clinical Trials 12:566-586 (1991)). Treatment strategies to achieve these goals follow the recommendations of the Joint National Commission on Detection, Evaluation, and Treatment of High Blood Pressure. Blood pressure is measured in the right arm after 5 minutes rest with a random-zero sphygmomanometer. Three consecutive readings are obtained with the patient sitting. The average of the last two measurements is taken as the visit blood pressure.\nA quality control program for each measurement and procedure was implemented and assessed in each clinical center and central facility. Quality control data were reviewed regularly by the Quality Control Committee and by the External Monitoring Committee and found to be acceptable.\n","PN","Follow-up Procedures and Measurements. Protein intake was assessed monthly on the basis of 24-hour urinary excretion of urea nitrogen. Nitrogen in the prescribed keto acid-amino acid supplement was subtracted from urinary urea nitrogen. The intake of protein, calories, and other nutrients was assessed every two months on the basis of three-day dietary records. Blood pressure was measured monthly, and when necessary, adjustments in therapy were made monthly or more often. The glomerular filtration rate was measured at two months, at four months, and every four months thereafter on the basis of the renal clearance of [125I) iothalamate (Isotex Diagnostics, Friendswood, Tex.). Anthropometric measurements were obtained every four months.","NI",null,"NI",null,"NI",null,"High","High ","Blood pressure was measured monthly, and when necessary, adjustments in therapy were made monthly or more often. No information is provoded for Q4.2 and Q4.12",null,null,"PY","the protocol was published in advance at “Design and Statistical Issues of the Modification of Diet in Renal Disease Trial. Controlled Clinical Trials 12:566-586 (1991)” and “The Modification of Diet in Renal Disease Study: Design, Methods, and Results From the Feasibility Study. American Journal of Kidney Diseases, Vol XX, No 1 (July), 1992: pp 18-33”.","PN","The database shows all required results","PN","Protocol and main article checked","Low","Low","The database shows all required results.",null,null,"High ","High ","There is some concern in one domain and high concern in another one."]
["2021/10/25 11.19",66,"JE","MDRD","MDRD 1994","Low targets","Standard targets","Number of antihypertensive drugs that each participant needed at the end of study"]

{"sheet":"Summary","index":2,"n_rows":67,"n_cols":33,"rows_kept":67,"cut":false,"hidden":false,"merged":[]}
["Unique ID","Reviewer","Study ID","Reference","Experimental","Comparator","Outcome","Result","Aim","Effect of adhering to intervention?","Weight","Randomization process","Comment for randomization process","Deviations from intended interventions","Comment for deviations from intended interventions","Missing outcome data","Comment for missing outcome data","Measurement of the outcome","Comment for measurement of the outcome","Selection of the reported result","Comment for selection of the reported result","Overall Bias","Comment for overall bias",null,null,null,null,"Randomization process","Deviations from intended interventions","Mising outcome data","Measurement of the outcome","Selection of the reported result","Overall Bias"]
[1,"JE","ACCORD","ACCORD 2010","Low targets","Standard targets","total mortality","RR=1.23","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Low",null,"Low",null,"Some concerns",null,null,null,null,"Assignment to intervention (the 'intention-to-treat' effect)"]
[2,"JE","ACCORD","ACCORD 2010","Low targets","Standard targets","total serious adverse events","RR=0.98","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Low",null,"Low",null,"Some concerns",null,null,null,null,"Total number of study = 55"]
[3,"JE","ACCORD","ACCORD 2010","Low targets","Standard targets","total cardiovascular events","RR=0.92","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Low",null,"Low",null,"Some concerns",null,null,null,null,"Low risk",100,0,81.8,50.9,100,0]
[4,"JE","ACCORD","ACCORD 2010","Low targets","Standard targets","cardiovascular mortality","RR=1.16","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Low",null,"Low",null,"Some concerns",null,null,null,null,"Some concerns",0,100,18.2,34.5,0,85.5]
[5,"JE","ACCORD","ACCORD 2010","Low targets","Standard targets","kidney failure","RR=0.51","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Low",null,"Low",null,"Some concerns",null,null,null,null,"High risk",0,0,0,1.8,0,1.8]
[6,"JE","ACCORD","ACCORD 2010","Low targets","Standard targets","Participant withdrawals due to adverse effects",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Adhering to intervention (the 'per-protocol' effect)"]
[7,"JE","ACCORD","ACCORD 2011","Low targets","Standard targets","Systolic blood pressure difference from baseline at one year","MD=12.90","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Low",null,"Low",null,"Some concerns",null,null,null,null,"Total number of study = 0"]
[8,"JE","ACCORD","ACCORD 2012","Low targets","Standard targets","Diastolic blood pressure difference from baseline at one year","MD=5.50","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Low",null,"Low",null,"Some concerns",null,null,null,null,"Low risk"]
[9,"JE","ACCORD","ACCORD 2013","Low targets","Standard targets","Doubling of serum creatinine level or 50% reduction in GFR at the end of study","RR=1.69","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Low",null,"Low",null,"Some concerns",null,null,null,null,"Some concerns"]
[10,"JE","ACCORD","ACCORD 2014","Low targets","Standard targets","Proportion of participants reaching target levels of blood pressure at the end of study","RR=0.74","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Low",null,"Low",null,"Some concerns",null,null,null,null,"High risk"]
[11,"JE","ACCORD","ACCORD 2015","Low targets","Standard targets","Number of antihypertensive drugs that each participant needed at the end of study","MD=1.30","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Low",null,"Low",null,"Some concerns"]
[12,"JE","HOT","HOT 1998","Low targets","Standard targets","total mortality","RR=1.10","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Some concerns",null,"Low",null,"Low",null,"Some concerns"]
[13,"JE","HOT","HOT 1998","Low targets","Standard targets","total serious adverse events","RR=1.13","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Some concerns",null,"Low",null,"Low",null,"Some concerns"]
[14,"JE","HOT","HOT 1998","Low targets","Standard targets","total cardiovascular events","RR=1.15","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Some concerns",null,"Low",null,"Low",null,"Some concerns"]
[15,"JE","HOT","HOT 1998","Low targets","Standard targets","cardiovascular mortality","RR=1.06","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Some concerns",null,"Low",null,"Low",null,"Some concerns"]
[16,"JE","HOT","HOT 1998","Low targets","Standard targets","kidney failure"]
[17,"JE","HOT","HOT 1998","Low targets","Standard targets","Participant withdrawals due to adverse effects","RR=0.98","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Some concerns",null,"Low",null,"Low",null,"Some concerns"]
[18,"JE","HOT","HOT 1998","Low targets","Standard targets","Systolic blood pressure difference from baseline at one year","MD=3.40","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Some concerns",null,"Low",null,"Low",null,"Some concerns"]
[19,"JE","HOT","HOT 1998","Low targets","Standard targets","Diastolic blood pressure difference from baseline at one year","MD=3.40","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Some concerns",null,"Low",null,"Low",null,"Some concerns"]
[20,"JE","HOT","HOT 1998","Low targets","Standard targets","Doubling of serum creatinine level or 50% reduction in GFR at the end of study","RR=0.80","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Some concerns",null,"Low",null,"Low",null,"Some concerns"]
[21,"JE","HOT","HOT 1998","Low targets","Standard targets","Proportion of participants reaching target levels of blood pressure at the end of study","RR=0.60","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Some concerns",null,"Low",null,"Low",null,"Some concerns"]
[22,"JE","HOT","HOT 1998","Low targets","Standard targets","Number of antihypertensive drugs that each participant needed at the end of study","MD=0.20","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Some concerns",null,"Low",null,"Low",null,"Some concerns"]
[23,"JE","AASK","AASK 2002","Low targets","Standard targets","total mortality","RR=0.71","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Some concerns",null,"Low",null,"Some concerns"]
[24,"JE","AASK","AASK 2002","Low targets","Standard targets","total serious adverse events","RR=0.94","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Some concerns",null,"Low",null,"Some concerns"]
[25,"JE","AASK","AASK 2002","Low targets","Standard targets","total cardiovascular events","RR=1.02","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Some concerns",null,"Low",null,"Some concerns"]
[26,"JE","AASK","AASK 2002","Low targets","Standard targets","cardiovascular mortality","RR=0.83","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Some concerns",null,"Low",null,"Some concerns"]
[27,"JE","AASK","AASK 2002","Low targets","Standard targets","kidney failure","RR=0.98","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Some concerns",null,"Low",null,"Some concerns"]
[28,"JE","AASK","AASK 2002","Low targets","Standard targets","Participant withdrawals due to adverse effects"]
[29,"JE","AASK","AASK 2002","Low targets","Standard targets","Systolic blood pressure difference from baseline at one year","MD=13.80","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Some concerns",null,"Low",null,"Some concerns"]
[30,"JE","AASK","AASK 2002","Low targets","Standard targets","Diastolic blood pressure difference from baseline at one year","MD=9.30","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Some concerns",null,"Low",null,"Some concerns"]
[31,"JE","AASK","AASK 2002","Low targets","Standard targets","Doubling of serum creatinine level or 50% reduction in GFR at the end of study","RR=1.53","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Some concerns",null,"Low",null,"Some concerns"]
[32,"JE","AASK","AASK 2002","Low targets","Standard targets","Proportion of participants reaching target levels of blood pressure at the end of study","RR=1.68","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Some concerns",null,"Low",null,"Some concerns"]
[33,"JE","AASK","AASK 2002","Low targets","Standard targets","Number of antihypertensive drugs that each participant needed at the end of study"]
[34,"JE","SPRINT","SPRINT 2015","Low targets","Standard targets","total mortality","RR=0.74","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Some concerns",null,"Low",null,"Some concerns"]
[35,"JE","SPRINT","SPRINT 2015","Low targets","Standard targets","total serious adverse events","RR=0.97","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Some concerns",null,"Low",null,"Some concerns"]
[36,"JE","SPRINT","SPRINT 2015","Low targets","Standard targets","total cardiovascular events","RR=0.83","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Some concerns",null,"Low",null,"Some concerns"]
[37,"JE","SPRINT","SPRINT 2015","Low targets","Standard targets","cardiovascular mortality","RR=0.61","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Some concerns",null,"Low",null,"Some concerns"]
[38,"JE","SPRINT","SPRINT 2015","Low targets","Standard targets","kidney failure","RR=0.59","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Some concerns",null,"Low",null,"Some concerns"]
[39,"JE","SPRINT","SPRINT 2015","Low targets","Standard targets","Participant withdrawals due to adverse effects"]
[40,"JE","SPRINT","SPRINT 2015","Low targets","Standard targets","Systolic blood pressure difference from baseline at one year","MD=13.18","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Some concerns",null,"Low",null,"Some concerns"]
[41,"JE","SPRINT","SPRINT 2015","Low targets","Standard targets","Diastolic blood pressure difference from baseline at one year","MD=7.42","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Some concerns",null,"Low",null,"Some concerns"]
[42,"JE","SPRINT","SPRINT 2015","Low targets","Standard targets","Doubling of serum creatinine level or 50% reduction in GFR at the end of study","RR=0.90","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Some concerns",null,"Low",null,"Some concerns"]
[43,"JE","SPRINT","SPRINT 2015","Low targets","Standard targets","Proportion of participants reaching target levels of blood pressure at the end of study","RR=0.88","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Some concerns",null,"Low",null,"Some concerns"]
[44,"JE","SPRINT","SPRINT 2015","Low targets","Standard targets","Number of antihypertensive drugs that each participant needed at the end of study","MD=0.91","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Some concerns",null,"Low",null,"Some concerns"]
[45,"JE","SPS3","SPS3 2013","Low targets","Standard targets","total mortality","RR=0.96","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Low",null,"Low",null,"Some concerns"]
[46,"JE","SPS3","SPS3 2013","Low targets","Standard targets","total serious adverse events","RR=1.26","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Low",null,"Low",null,"Some concerns"]
[47,"JE","SPS3","SPS3 2013","Low targets","Standard targets","total cardiovascular events","RR=1.34","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Low",null,"Low",null,"Some concerns"]
[48,"JE","SPS3","SPS3 2013","Low targets","Standard targets","cardiovascular mortality","RR=0.87","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Low",null,"Low",null,"Some concerns"]
[49,"JE","SPS3","SPS3 2013","Low targets","Standard targets","kidney failure",null,null,null,null,null,null,null,null,null,null,"Low",null,"Low",null,"Some concerns"]
[50,"JE","SPS3","SPS3 2013","Low targets","Standard targets","Participant withdrawals due to adverse effects",null,null,null,null,null,null,null,null,null,null,"Low",null,"Low",null,"Some concerns"]
[51,"JE","SPS3","SPS3 2013","Low targets","Standard targets","Systolic blood pressure difference from baseline at one year","MD=8.00","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Low",null,"Low",null,"Some concerns"]
[52,"JE","SPS3","SPS3 2013","Low targets","Standard targets","Diastolic blood pressure difference from baseline at one year","MD=4.30","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Low",null,"Low",null,"Some concerns"]
[53,"JE","SPS3","SPS3 2013","Low targets","Standard targets","Doubling of serum creatinine level or 50% reduction in GFR at the end of study",null,null,null,null,null,null,null,null,null,null,"Low",null,"Low",null,"Some concerns"]
[54,"JE","SPS3","SPS3 2013","Low targets","Standard targets","Proportion of participants reaching target levels of blood pressure at the end of study","RR=1.30","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Low",null,"Low",null,"Some concerns"]
[55,"JE","SPS3","SPS3 2013","Low targets","Standard targets","Number of antihypertensive drugs that each participant needed at the end of study","MD=0.50","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"Low",null,"Low",null,"Some concerns"]
[56,"JE","MDRD","MDRD 1994","Low targets","Standard targets","total mortality","RR=1.35","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"High",null,"Low",null,"High "]
[57,"JE","MDRD","MDRD 1994","Low targets","Standard targets","total serious adverse events","RR=1.12","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"High ",null,"Low",null,"High "]
[58,"JE","MDRD","MDRD 1994","Low targets","Standard targets","total cardiovascular events"]
[59,"JE","MDRD","MDRD 1994","Low targets","Standard targets","cardiovascular mortality","RR=1.42","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"High ",null,"Low",null,"High "]
[60,"JE","MDRD","MDRD 1994","Low targets","Standard targets","kidney failure","RR=0.98","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"High ",null,"Low",null,"High "]
[61,"JE","MDRD","MDRD 1994","Low targets","Standard targets","Participant withdrawals due to adverse effects"]
[62,"JE","MDRD","MDRD 1994","Low targets","Standard targets","Systolic blood pressure difference from baseline at one year","MD=5.30","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"High ",null,"Low",null,"High"]
[63,"JE","MDRD","MDRD 1994","Low targets","Standard targets","Diastolic blood pressure difference from baseline at one year","MD=4.00","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"High ",null,"Low",null,"High "]
[64,"JE","MDRD","MDRD 1994","Low targets","Standard targets","Doubling of serum creatinine level or 50% reduction in GFR at the end of study","RR=0.67","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"High ",null,"Low",null,"High "]
[65,"JE","MDRD","MDRD 1994","Low targets","Standard targets","Proportion of participants reaching target levels of blood pressure at the end of study","RR=0.65","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Low",null,"Some concerns",null,"Low",null,"High ",null,"Low",null,"High "]
[66,"JE","MDRD","MDRD 1994","Low targets","Standard targets","Number of antihypertensive drugs that each participant needed at the end of study"]

{"sheet":"Figure (ITT)","index":3,"n_rows":56,"n_cols":16,"rows_kept":56,"cut":false,"hidden":false,"merged":[]}
["Intention-to-treat","Unique ID","Study ID","Experimental","Comparator","Outcome","Weight","D1","D2","D3","D4","D5","Overall"]
[null,1,"ACCORD","Low targets","Standard targets","total mortality",1,null,null,null,null,null,null,null,null,"Low risk"]
[null,2,"ACCORD","Low targets","Standard targets","total serious adverse events",1,null,null,null,null,null,null,null,null,"Some concerns"]
[null,3,"ACCORD","Low targets","Standard targets","total cardiovascular events",1,null,null,null,null,null,null,null,null,"High risk"]
[null,4,"ACCORD","Low targets","Standard targets","cardiovascular mortality",1]
[null,5,"ACCORD","Low targets","Standard targets","kidney failure",1,null,null,null,null,null,null,null,"D1","Randomisation process"]
[null,7,"ACCORD","Low targets","Standard targets","Systolic blood pressure difference from baseline at one year",1,null,null,null,null,null,null,null,"D2","Deviations from the intended interventions"]
[null,8,"ACCORD","Low targets","Standard targets","Diastolic blood pressure difference from baseline at one year",1,null,null,null,null,null,null,null,"D3","Missing outcome data"]
[null,9,"ACCORD","Low targets","Standard targets","Doubling of serum creatinine level or 50% reduction in GFR at the end of study",1,null,null,null,null,null,null,null,"D4","Measurement of the outcome"]
[null,10,"ACCORD","Low targets","Standard targets","Proportion of participants reaching target levels of blood pressure at the end of study",1,null,null,null,null,null,null,null,"D5","Selection of the reported result"]
[null,11,"ACCORD","Low targets","Standard targets","Number of antihypertensive drugs that each participant needed at the end of study",1]
[null,12,"HOT","Low targets","Standard targets","total mortality",1]
[null,13,"HOT","Low targets","Standard targets","total serious adverse events",1]
[null,14,"HOT","Low targets","Standard targets","total cardiovascular events",1]
[null,15,"HOT","Low targets","Standard targets","cardiovascular mortality",1]
[null,17,"HOT","Low targets","Standard targets","Participant withdrawals due to adverse effects",1]
[null,18,"HOT","Low targets","Standard targets","Systolic blood pressure difference from baseline at one year",1]
[null,19,"HOT","Low targets","Standard targets","Diastolic blood pressure difference from baseline at one year",1]
[null,20,"HOT","Low targets","Standard targets","Doubling of serum creatinine level or 50% reduction in GFR at the end of study",1]
[null,21,"HOT","Low targets","Standard targets","Proportion of participants reaching target levels of blood pressure at the end of study",1]
[null,22,"HOT","Low targets","Standard targets","Number of antihypertensive drugs that each participant needed at the end of study",1]
[null,23,"AASK","Low targets","Standard targets","total mortality",1]
[null,24,"AASK","Low targets","Standard targets","total serious adverse events",1]
[null,25,"AASK","Low targets","Standard targets","total cardiovascular events",1]
[null,26,"AASK","Low targets","Standard targets","cardiovascular mortality",1]
[null,27,"AASK","Low targets","Standard targets","kidney failure",1]
[null,29,"AASK","Low targets","Standard targets","Systolic blood pressure difference from baseline at one year",1]
[null,30,"AASK","Low targets","Standard targets","Diastolic blood pressure difference from baseline at one year",1]
[null,31,"AASK","Low targets","Standard targets","Doubling of serum creatinine level or 50% reduction in GFR at the end of study",1]
[null,32,"AASK","Low targets","Standard targets","Proportion of participants reaching target levels of blood pressure at the end of study",1]
[null,34,"SPRINT","Low targets","Standard targets","total mortality",1]
[null,35,"SPRINT","Low targets","Standard targets","total serious adverse events",1]
[null,36,"SPRINT","Low targets","Standard targets","total cardiovascular events",1]
[null,37,"SPRINT","Low targets","Standard targets","cardiovascular mortality",1]
[null,38,"SPRINT","Low targets","Standard targets","kidney failure",1]
[null,40,"SPRINT","Low targets","Standard targets","Systolic blood pressure difference from baseline at one year",1]
[null,41,"SPRINT","Low targets","Standard targets","Diastolic blood pressure difference from baseline at one year",1]
[null,42,"SPRINT","Low targets","Standard targets","Doubling of serum creatinine level or 50% reduction in GFR at the end of study",1]
[null,43,"SPRINT","Low targets","Standard targets","Proportion of participants reaching target levels of blood pressure at the end of study",1]
[null,44,"SPRINT","Low targets","Standard targets","Number of antihypertensive drugs that each participant needed at the end of study",1]
[null,45,"SPS3","Low targets","Standard targets","total mortality",1]
[null,46,"SPS3","Low targets","Standard targets","total serious adverse events",1]
[null,47,"SPS3","Low targets","Standard targets","total cardiovascular events",1]
[null,48,"SPS3","Low targets","Standard targets","cardiovascular mortality",1]
[null,51,"SPS3","Low targets","Standard targets","Systolic blood pressure difference from baseline at one year",1]
[null,52,"SPS3","Low targets","Standard targets","Diastolic blood pressure difference from baseline at one year",1]
[null,54,"SPS3","Low targets","Standard targets","Proportion of participants reaching target levels of blood pressure at the end of study",1]
[null,55,"SPS3","Low targets","Standard targets","Number of antihypertensive drugs that each participant needed at the end of study",1]
[null,56,"MDRD","Low targets","Standard targets","total mortality",1]
[null,57,"MDRD","Low targets","Standard targets","total serious adverse events",1]
[null,59,"MDRD","Low targets","Standard targets","cardiovascular mortality",1]
[null,60,"MDRD","Low targets","Standard targets","kidney failure",1]
[null,62,"MDRD","Low targets","Standard targets","Systolic blood pressure difference from baseline at one year",1]
[null,63,"MDRD","Low targets","Standard targets","Diastolic blood pressure difference from baseline at one year",1]
[null,64,"MDRD","Low targets","Standard targets","Doubling of serum creatinine level or 50% reduction in GFR at the end of study",1]
[null,65,"MDRD","Low targets","Standard targets","Proportion of participants reaching target levels of blood pressure at the end of study",1]

{"sheet":"Figure (PP)","index":4,"n_rows":1,"n_cols":13,"rows_kept":1,"cut":false,"hidden":false,"merged":[]}
["Per-protocol","Unique ID","Study ID","Experimental","Comparator","Outcome","Weight","D1","D2","D3","D4","D5","Overall"]

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["Unique ID",1,"Study ID","ACCORD","Assessor","JE"]
["Ref or Label","ACCORD 2010","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","total mortality","Results","RR=1.23","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"PY","An internet-based, web browser randomization procedure was employed"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","Described in Table 1 of the main article"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","This is an unmasked open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NI"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","Primary comparisons of intervention groups will be performed according to the intention-to-treat principle. All randomized participants in these analyses will be grouped according to their intervention assignment at randomization, regardless of adherence."]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","Consort diagram. Section 1"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","The primary endpoint for ACCORD is the composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Cardiovascular death are defined in Section 5.1.a, myocardial infarctions are defined in Section 5.1.b, and strokes are defined in Section 5.1.c"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","Additional visits can be scheduled as needed to monitor and assure appropriate implementation of the study interventions. For the purpose of event ascertainment, all participants in all treatment groups will be queried regarding the occurrence of a possible event on the same schedule, specifically every 4 months."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"NI","ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death). Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",2,"Study ID","ACCORD","Assessor","JE"]
["Ref or Label","ACCORD 2010","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","total serious adverse events","Results","RR=0.98","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"PY","An internet-based, web browser randomization procedure was employed"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","Described in Table 1 of the main article"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","This is an unmasked open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","Primary comparisons of intervention groups will be performed according to the intention-to-treat principle. All randomized participants in these analyses will be grouped according to their intervention assignment at randomization, regardless of adherence."]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","Consort diagram. Section 2"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","The primary endpoint for ACCORD is the composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Cardiovascular death are defined in Section 5.1.a, myocardial infarctions are defined in Section 5.1.b, and strokes are defined in Section 5.1.c"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","Additional visits can be scheduled as needed to monitor and assure appropriate implementation of the study interventions. For the purpose of event ascertainment, all participants in all treatment groups will be queried regarding the occurrence of a possible event on the same schedule, specifically every 4 months."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death). Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",3,"Study ID","ACCORD","Assessor","JE"]
["Ref or Label","ACCORD 2010","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","total cardiovascular events","Results","RR=0.92","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"PY","An internet-based, web browser randomization procedure was employed"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","Described in Table 1 of the main article"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","This is an unmasked open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","Primary comparisons of intervention groups will be performed according to the intention-to-treat principle. All randomized participants in these analyses will be grouped according to their intervention assignment at randomization, regardless of adherence."]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","Consort diagram. Section 3"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","The primary endpoint for ACCORD is the composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Cardiovascular death are defined in Section 5.1.a, myocardial infarctions are defined in Section 5.1.b, and strokes are defined in Section 5.1.c"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","Additional visits can be scheduled as needed to monitor and assure appropriate implementation of the study interventions. For the purpose of event ascertainment, all participants in all treatment groups will be queried regarding the occurrence of a possible event on the same schedule, specifically every 4 months."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death). Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",4,"Study ID","ACCORD","Assessor","JE"]
["Ref or Label","ACCORD 2010","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","cardiovascular mortality","Results","RR=1.16","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"PY","An internet-based, web browser randomization procedure was employed"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","Described in Table 1 of the main article"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","This is an unmasked open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","Primary comparisons of intervention groups will be performed according to the intention-to-treat principle. All randomized participants in these analyses will be grouped according to their intervention assignment at randomization, regardless of adherence."]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","Consort diagram. Section 4"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","The primary endpoint for ACCORD is the composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Cardiovascular death are defined in Section 5.1.a, myocardial infarctions are defined in Section 5.1.b, and strokes are defined in Section 5.1.c"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","Additional visits can be scheduled as needed to monitor and assure appropriate implementation of the study interventions. For the purpose of event ascertainment, all participants in all treatment groups will be queried regarding the occurrence of a possible event on the same schedule, specifically every 4 months."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death). Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",5,"Study ID","ACCORD","Assessor","JE"]
["Ref or Label","ACCORD 2010","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","kidney failure","Results","RR=0.51","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"PY","An internet-based, web browser randomization procedure was employed"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","Described in Table 1 of the main article"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","This is an unmasked open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","Primary comparisons of intervention groups will be performed according to the intention-to-treat principle. All randomized participants in these analyses will be grouped according to their intervention assignment at randomization, regardless of adherence."]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","Consort diagram. Section 5"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","The primary endpoint for ACCORD is the composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Cardiovascular death are defined in Section 5.1.a, myocardial infarctions are defined in Section 5.1.b, and strokes are defined in Section 5.1.c"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","Additional visits can be scheduled as needed to monitor and assure appropriate implementation of the study interventions. For the purpose of event ascertainment, all participants in all treatment groups will be queried regarding the occurrence of a possible event on the same schedule, specifically every 4 months."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death). Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
[]
[]
["Unique ID",7,"Study ID","ACCORD","Assessor","JE"]
["Ref or Label","ACCORD 2011","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","Systolic blood pressure difference from baseline at one year","Results","MD=12.90","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"PY","An internet-based, web browser randomization procedure was employed"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","Described in Table 1 of the main article"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","This is an unmasked open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","Primary comparisons of intervention groups will be performed according to the intention-to-treat principle. All randomized participants in these analyses will be grouped according to their intervention assignment at randomization, regardless of adherence."]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","Consort diagram. Section 7"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","The primary endpoint for ACCORD is the composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Cardiovascular death are defined in Section 5.1.a, myocardial infarctions are defined in Section 5.1.b, and strokes are defined in Section 5.1.c"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","Additional visits can be scheduled as needed to monitor and assure appropriate implementation of the study interventions. For the purpose of event ascertainment, all participants in all treatment groups will be queried regarding the occurrence of a possible event on the same schedule, specifically every 4 months."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death). Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",8,"Study ID","ACCORD","Assessor","JE"]
["Ref or Label","ACCORD 2012","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","Diastolic blood pressure difference from baseline at one year","Results","MD=5.50","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"PY","An internet-based, web browser randomization procedure was employed"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","Described in Table 1 of the main article"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","This is an unmasked open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","Primary comparisons of intervention groups will be performed according to the intention-to-treat principle. All randomized participants in these analyses will be grouped according to their intervention assignment at randomization, regardless of adherence."]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","Consort diagram. Section 8"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","The primary endpoint for ACCORD is the composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Cardiovascular death are defined in Section 5.1.a, myocardial infarctions are defined in Section 5.1.b, and strokes are defined in Section 5.1.c"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","Additional visits can be scheduled as needed to monitor and assure appropriate implementation of the study interventions. For the purpose of event ascertainment, all participants in all treatment groups will be queried regarding the occurrence of a possible event on the same schedule, specifically every 4 months."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death). Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",9,"Study ID","ACCORD","Assessor","JE"]
["Ref or Label","ACCORD 2013","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","Doubling of serum creatinine level or 50% reduction in GFR at the end of study","Results","RR=1.69","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"PY","An internet-based, web browser randomization procedure was employed"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","Described in Table 1 of the main article"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","This is an unmasked open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","Primary comparisons of intervention groups will be performed according to the intention-to-treat principle. All randomized participants in these analyses will be grouped according to their intervention assignment at randomization, regardless of adherence."]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","Consort diagram. Section 9"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","The primary endpoint for ACCORD is the composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Cardiovascular death are defined in Section 5.1.a, myocardial infarctions are defined in Section 5.1.b, and strokes are defined in Section 5.1.c"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","Additional visits can be scheduled as needed to monitor and assure appropriate implementation of the study interventions. For the purpose of event ascertainment, all participants in all treatment groups will be queried regarding the occurrence of a possible event on the same schedule, specifically every 4 months."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death). Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",10,"Study ID","ACCORD","Assessor","JE"]
["Ref or Label","ACCORD 2014","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","Proportion of participants reaching target levels of blood pressure at the end of study","Results","RR=0.74","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"PY","An internet-based, web browser randomization procedure was employed"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","Described in Table 1 of the main article"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","This is an unmasked open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","Primary comparisons of intervention groups will be performed according to the intention-to-treat principle. All randomized participants in these analyses will be grouped according to their intervention assignment at randomization, regardless of adherence."]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","Consort diagram. Section 10"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","The primary endpoint for ACCORD is the composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Cardiovascular death are defined in Section 5.1.a, myocardial infarctions are defined in Section 5.1.b, and strokes are defined in Section 5.1.c"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","Additional visits can be scheduled as needed to monitor and assure appropriate implementation of the study interventions. For the purpose of event ascertainment, all participants in all treatment groups will be queried regarding the occurrence of a possible event on the same schedule, specifically every 4 months."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death). Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",11,"Study ID","ACCORD","Assessor","JE"]
["Ref or Label","ACCORD 2015","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","Number of antihypertensive drugs that each participant needed at the end of study","Results","MD=1.30","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"PY","An internet-based, web browser randomization procedure was employed"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","Described in Table 1 of the main article"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","This is an unmasked open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","Primary comparisons of intervention groups will be performed according to the intention-to-treat principle. All randomized participants in these analyses will be grouped according to their intervention assignment at randomization, regardless of adherence."]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","Consort diagram. Section 11"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","The primary endpoint for ACCORD is the composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Cardiovascular death are defined in Section 5.1.a, myocardial infarctions are defined in Section 5.1.b, and strokes are defined in Section 5.1.c"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","Additional visits can be scheduled as needed to monitor and assure appropriate implementation of the study interventions. For the purpose of event ascertainment, all participants in all treatment groups will be queried regarding the occurrence of a possible event on the same schedule, specifically every 4 months."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","ACCORD utilized a centralized adjudication process for all deaths, and hospitalizations for myocardial infarction and strokes. Upon identification of a potential outcome, clinical site staff obtained medical records (if the outcome was a hospitalization) or details regarding the case (if the case was an out-of-hospital death). Personal identifiers and information that may have alerted adjudicators to treatment assignment (e.g. A1C values) were masked by the clinical site and the medical records sent to the Coordinating Center. At the Coordinating Center, the case was assigned to two reviewers who completed their adjudication independently."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (Protocol, page 3). The primary outcome for all three ACCORD trials was the first occurrence of a major cardiovascular event, which was defined as the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. (NEJM article, page 1577)"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",12,"Study ID","HOT","Assessor","JE"]
["Ref or Label","HOT 1998","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol; Regulatory document (e.g. Clinical Study Report, Drug Approval Package)"]
["Outcome","total mortality","Results","RR=1.10","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"PY","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975)."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","There doesn't seem to be a significant imbalance in follow-up diagram"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PN","No significant differences among targets have been detected. However, 14% of the ECG could not be obtained leading to uncertainty on silent myocardial infarctions"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Effect variables defined in the protocol"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","The first follow·up visit is scheduled 3 months after the Randomi·\nsation Visit. The next follow-up visit will take place 6 months after the Randomisation Visit and thereafter visits will take place every 6 months. Current antihypertensive medication as well as seated blood pressure and heart rate are recorded. Clinical events and side effects occurring since previous visit are recorded . It is up to the investigator to judge if visits are needed more frequently. However, no data will be collected at such extra visits."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","The study is a prospective, randomised, open trial with blinded\nclinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"N","The database shows all required results"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"N","The database shows all required results"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",13,"Study ID","HOT","Assessor","JE"]
["Ref or Label","HOT 1998","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol; Regulatory document (e.g. Clinical Study Report, Drug Approval Package)"]
["Outcome","total serious adverse events","Results","RR=1.13","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"PY","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975)."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","There doesn't seem to be a significant imbalance in follow-up diagram"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PN","No significant differences among targets have been detected. However, 14% of the ECG could not be obtained leading to uncertainty on silent myocardial infarctions"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Effect variables defined in the protocol"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","The first follow·up visit is scheduled 3 months after the Randomi·\nsation Visit. The next follow-up visit will take place 6 months after the Randomisation Visit and thereafter visits will take place every 6 months. Current antihypertensive medication as well as seated blood pressure and heart rate are recorded. Clinical events and side effects occurring since previous visit are recorded . It is up to the investigator to judge if visits are needed more frequently. However, no data will be collected at such extra visits."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","The study is a prospective, randomised, open trial with blinded\nclinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"N","The database shows all required results"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"N","The database shows all required results"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",14,"Study ID","HOT","Assessor","JE"]
["Ref or Label","HOT 1998","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol; Regulatory document (e.g. Clinical Study Report, Drug Approval Package)"]
["Outcome","total cardiovascular events","Results","RR=1.15","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"PY","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975)."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","There doesn't seem to be a significant imbalance in follow-up diagram"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PN","No significant differences among targets have been detected. However, 14% of the ECG could not be obtained leading to uncertainty on silent myocardial infarctions"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Effect variables defined in the protocol"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","The first follow·up visit is scheduled 3 months after the Randomi·\nsation Visit. The next follow-up visit will take place 6 months after the Randomisation Visit and thereafter visits will take place every 6 months. Current antihypertensive medication as well as seated blood pressure and heart rate are recorded. Clinical events and side effects occurring since previous visit are recorded . It is up to the investigator to judge if visits are needed more frequently. However, no data will be collected at such extra visits."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","The study is a prospective, randomised, open trial with blinded\nclinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"N","The database shows all required results"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"N","The database shows all required results"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",15,"Study ID","HOT","Assessor","JE"]
["Ref or Label","HOT 1998","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol; Regulatory document (e.g. Clinical Study Report, Drug Approval Package)"]
["Outcome","cardiovascular mortality","Results","RR=1.06","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"PY","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975)."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","There doesn't seem to be a significant imbalance in follow-up diagram"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PN","No significant differences among targets have been detected. However, 14% of the ECG could not be obtained leading to uncertainty on silent myocardial infarctions"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Effect variables defined in the protocol"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","The first follow·up visit is scheduled 3 months after the Randomi·\nsation Visit. The next follow-up visit will take place 6 months after the Randomisation Visit and thereafter visits will take place every 6 months. Current antihypertensive medication as well as seated blood pressure and heart rate are recorded. Clinical events and side effects occurring since previous visit are recorded . It is up to the investigator to judge if visits are needed more frequently. However, no data will be collected at such extra visits."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","The study is a prospective, randomised, open trial with blinded\nclinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"N","The database shows all required results"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"N","The database shows all required results"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
[]
[]
["Unique ID",17,"Study ID","HOT","Assessor","JE"]
["Ref or Label","HOT 1998","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol; Regulatory document (e.g. Clinical Study Report, Drug Approval Package)"]
["Outcome","Participant withdrawals due to adverse effects","Results","RR=0.98","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"PY","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975)."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","There doesn't seem to be a significant imbalance in follow-up diagram"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PN","No significant differences among targets have been detected. However, 14% of the ECG could not be obtained leading to uncertainty on silent myocardial infarctions"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Effect variables defined in the protocol"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","The first follow·up visit is scheduled 3 months after the Randomi·\nsation Visit. The next follow-up visit will take place 6 months after the Randomisation Visit and thereafter visits will take place every 6 months. Current antihypertensive medication as well as seated blood pressure and heart rate are recorded. Clinical events and side effects occurring since previous visit are recorded . It is up to the investigator to judge if visits are needed more frequently. However, no data will be collected at such extra visits."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","The study is a prospective, randomised, open trial with blinded\nclinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"N","The database shows all required results"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"N","The database shows all required results"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",18,"Study ID","HOT","Assessor","JE"]
["Ref or Label","HOT 1998","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol; Regulatory document (e.g. Clinical Study Report, Drug Approval Package)"]
["Outcome","Systolic blood pressure difference from baseline at one year","Results","MD=3.40","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"PY","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975)."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","There doesn't seem to be a significant imbalance in follow-up diagram"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PN","No significant differences among targets have been detected. However, 14% of the ECG could not be obtained leading to uncertainty on silent myocardial infarctions"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Effect variables defined in the protocol"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","The first follow·up visit is scheduled 3 months after the Randomi·\nsation Visit. The next follow-up visit will take place 6 months after the Randomisation Visit and thereafter visits will take place every 6 months. Current antihypertensive medication as well as seated blood pressure and heart rate are recorded. Clinical events and side effects occurring since previous visit are recorded . It is up to the investigator to judge if visits are needed more frequently. However, no data will be collected at such extra visits."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","The study is a prospective, randomised, open trial with blinded\nclinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"N","The database shows all required results"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"N","The database shows all required results"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",19,"Study ID","HOT","Assessor","JE"]
["Ref or Label","HOT 1998","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol; Regulatory document (e.g. Clinical Study Report, Drug Approval Package)"]
["Outcome","Diastolic blood pressure difference from baseline at one year","Results","MD=3.40","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"PY","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975)."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","There doesn't seem to be a significant imbalance in follow-up diagram"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PN","No significant differences among targets have been detected. However, 14% of the ECG could not be obtained leading to uncertainty on silent myocardial infarctions"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Effect variables defined in the protocol"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","The first follow·up visit is scheduled 3 months after the Randomi·\nsation Visit. The next follow-up visit will take place 6 months after the Randomisation Visit and thereafter visits will take place every 6 months. Current antihypertensive medication as well as seated blood pressure and heart rate are recorded. Clinical events and side effects occurring since previous visit are recorded . It is up to the investigator to judge if visits are needed more frequently. However, no data will be collected at such extra visits."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","The study is a prospective, randomised, open trial with blinded\nclinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"N","The database shows all required results"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"N","The database shows all required results"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",20,"Study ID","HOT","Assessor","JE"]
["Ref or Label","HOT 1998","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol; Regulatory document (e.g. Clinical Study Report, Drug Approval Package)"]
["Outcome","Doubling of serum creatinine level or 50% reduction in GFR at the end of study","Results","RR=0.80","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"PY","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975)."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","There doesn't seem to be a significant imbalance in follow-up diagram"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PN","No significant differences among targets have been detected. However, 14% of the ECG could not be obtained leading to uncertainty on silent myocardial infarctions"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Effect variables defined in the protocol"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","The first follow·up visit is scheduled 3 months after the Randomi·\nsation Visit. The next follow-up visit will take place 6 months after the Randomisation Visit and thereafter visits will take place every 6 months. Current antihypertensive medication as well as seated blood pressure and heart rate are recorded. Clinical events and side effects occurring since previous visit are recorded . It is up to the investigator to judge if visits are needed more frequently. However, no data will be collected at such extra visits."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","The study is a prospective, randomised, open trial with blinded\nclinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"N","The database shows all required results"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"N","The database shows all required results"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",21,"Study ID","HOT","Assessor","JE"]
["Ref or Label","HOT 1998","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol; Regulatory document (e.g. Clinical Study Report, Drug Approval Package)"]
["Outcome","Proportion of participants reaching target levels of blood pressure at the end of study","Results","RR=0.60","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"PY","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975)."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","There doesn't seem to be a significant imbalance in follow-up diagram"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PN","No significant differences among targets have been detected. However, 14% of the ECG could not be obtained leading to uncertainty on silent myocardial infarctions"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Effect variables defined in the protocol"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","The first follow·up visit is scheduled 3 months after the Randomi·\nsation Visit. The next follow-up visit will take place 6 months after the Randomisation Visit and thereafter visits will take place every 6 months. Current antihypertensive medication as well as seated blood pressure and heart rate are recorded. Clinical events and side effects occurring since previous visit are recorded . It is up to the investigator to judge if visits are needed more frequently. However, no data will be collected at such extra visits."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","The study is a prospective, randomised, open trial with blinded\nclinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"N","The database shows all required results"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"N","The database shows all required results"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",22,"Study ID","HOT","Assessor","JE"]
["Ref or Label","HOT 1998","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol; Regulatory document (e.g. Clinical Study Report, Drug Approval Package)"]
["Outcome","Number of antihypertensive drugs that each participant needed at the end of study","Results","MD=0.20","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"PY","The randomisation to target diastolic blood pressure group and to low·dose ASA or placebo, respectively, will be performed centrally. The randomisation procedure is a version of the Pocock-Simon randomisation (Pocock SJ, 1975)."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","There doesn't seem to be a significant imbalance in follow-up diagram"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PN","No significant differences among targets have been detected. However, 14% of the ECG could not be obtained leading to uncertainty on silent myocardial infarctions"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Effect variables defined in the protocol"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","The first follow·up visit is scheduled 3 months after the Randomi·\nsation Visit. The next follow-up visit will take place 6 months after the Randomisation Visit and thereafter visits will take place every 6 months. Current antihypertensive medication as well as seated blood pressure and heart rate are recorded. Clinical events and side effects occurring since previous visit are recorded . It is up to the investigator to judge if visits are needed more frequently. However, no data will be collected at such extra visits."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","The study is a prospective, randomised, open trial with blinded\nclinical events evaluation (PROBE) regarding the relationship\nbetween target blood pressure and cardiovascular morbidity and mortality."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"N","The database shows all required results"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"N","The database shows all required results"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",23,"Study ID","AASK","Assessor","JE"]
["Ref or Label","AASK 2002","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","total mortality","Results","RR=0.71","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Computer-based randomization"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","No significant imbalance in the flow chart"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PY","No significant differences between groups"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"PN","Renal outcomes defined in protocol. "]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"NA","Interim visits will occur as frequently as necessary in between scheduled protocol follow-up visits. They may be for measurements for evaluation of protocol safety issues (e.g. Action Items, laboratory tests) or held electively. These visits will help ensure that participant's assigned MAP goals are achieved or maintained by adjustment of antihypertensive agents."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalized cardiovascular events are reviewed and classified by a blinded endpoints committee according to a prespecified protocol."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The database shows all required results"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","The database shows all required results"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",24,"Study ID","AASK","Assessor","JE"]
["Ref or Label","AASK 2002","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","total serious adverse events","Results","RR=0.94","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Computer-based randomization"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","No significant imbalance in the flow chart"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PY","No significant differences between groups"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"PN","Renal outcomes defined in protocol. "]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"NA","Interim visits will occur as frequently as necessary in between scheduled protocol follow-up visits. They may be for measurements for evaluation of protocol safety issues (e.g. Action Items, laboratory tests) or held electively. These visits will help ensure that participant's assigned MAP goals are achieved or maintained by adjustment of antihypertensive agents."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalized cardiovascular events are reviewed and classified by a blinded endpoints committee according to a prespecified protocol."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The database shows all required results"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","The database shows all required results"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",25,"Study ID","AASK","Assessor","JE"]
["Ref or Label","AASK 2002","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","total cardiovascular events","Results","RR=1.02","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Computer-based randomization"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","No significant imbalance in the flow chart"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PY","No significant differences between groups"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"PN","Renal outcomes defined in protocol. "]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"NA","Interim visits will occur as frequently as necessary in between scheduled protocol follow-up visits. They may be for measurements for evaluation of protocol safety issues (e.g. Action Items, laboratory tests) or held electively. These visits will help ensure that participant's assigned MAP goals are achieved or maintained by adjustment of antihypertensive agents."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalized cardiovascular events are reviewed and classified by a blinded endpoints committee according to a prespecified protocol."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The database shows all required results"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","The database shows all required results"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",26,"Study ID","AASK","Assessor","JE"]
["Ref or Label","AASK 2002","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","cardiovascular mortality","Results","RR=0.83","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Computer-based randomization"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","No significant imbalance in the flow chart"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PY","No significant differences between groups"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"PN","Renal outcomes defined in protocol. "]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"NA","Interim visits will occur as frequently as necessary in between scheduled protocol follow-up visits. They may be for measurements for evaluation of protocol safety issues (e.g. Action Items, laboratory tests) or held electively. These visits will help ensure that participant's assigned MAP goals are achieved or maintained by adjustment of antihypertensive agents."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalized cardiovascular events are reviewed and classified by a blinded endpoints committee according to a prespecified protocol."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The database shows all required results"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","The database shows all required results"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",27,"Study ID","AASK","Assessor","JE"]
["Ref or Label","AASK 2002","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","kidney failure","Results","RR=0.98","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Computer-based randomization"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","No significant imbalance in the flow chart"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PY","No significant differences between groups"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"PN","Renal outcomes defined in protocol. "]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"NA","Interim visits will occur as frequently as necessary in between scheduled protocol follow-up visits. They may be for measurements for evaluation of protocol safety issues (e.g. Action Items, laboratory tests) or held electively. These visits will help ensure that participant's assigned MAP goals are achieved or maintained by adjustment of antihypertensive agents."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalized cardiovascular events are reviewed and classified by a blinded endpoints committee according to a prespecified protocol."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The database shows all required results"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","The database shows all required results"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
[]
[]
["Unique ID",29,"Study ID","AASK","Assessor","JE"]
["Ref or Label","AASK 2002","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","Systolic blood pressure difference from baseline at one year","Results","MD=13.80","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Computer-based randomization"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","No significant imbalance in the flow chart"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PY","No significant differences between groups"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"PN","Renal outcomes defined in protocol. "]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"NA","Interim visits will occur as frequently as necessary in between scheduled protocol follow-up visits. They may be for measurements for evaluation of protocol safety issues (e.g. Action Items, laboratory tests) or held electively. These visits will help ensure that participant's assigned MAP goals are achieved or maintained by adjustment of antihypertensive agents."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalized cardiovascular events are reviewed and classified by a blinded endpoints committee according to a prespecified protocol."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The database shows all required results"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","The database shows all required results"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",30,"Study ID","AASK","Assessor","JE"]
["Ref or Label","AASK 2002","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","Diastolic blood pressure difference from baseline at one year","Results","MD=9.30","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Computer-based randomization"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","No significant imbalance in the flow chart"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PY","No significant differences between groups"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"PN","Renal outcomes defined in protocol. "]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"NA","Interim visits will occur as frequently as necessary in between scheduled protocol follow-up visits. They may be for measurements for evaluation of protocol safety issues (e.g. Action Items, laboratory tests) or held electively. These visits will help ensure that participant's assigned MAP goals are achieved or maintained by adjustment of antihypertensive agents."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalized cardiovascular events are reviewed and classified by a blinded endpoints committee according to a prespecified protocol."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The database shows all required results"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","The database shows all required results"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",31,"Study ID","AASK","Assessor","JE"]
["Ref or Label","AASK 2002","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","Doubling of serum creatinine level or 50% reduction in GFR at the end of study","Results","RR=1.53","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Computer-based randomization"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","No significant imbalance in the flow chart"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PY","No significant differences between groups"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"PN","Renal outcomes defined in protocol. "]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"NA","Interim visits will occur as frequently as necessary in between scheduled protocol follow-up visits. They may be for measurements for evaluation of protocol safety issues (e.g. Action Items, laboratory tests) or held electively. These visits will help ensure that participant's assigned MAP goals are achieved or maintained by adjustment of antihypertensive agents."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalized cardiovascular events are reviewed and classified by a blinded endpoints committee according to a prespecified protocol."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The database shows all required results"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","The database shows all required results"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",32,"Study ID","AASK","Assessor","JE"]
["Ref or Label","AASK 2002","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","Proportion of participants reaching target levels of blood pressure at the end of study","Results","RR=1.68","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Computer-based randomization"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","No significant imbalance in the flow chart"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PY","No significant differences between groups"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"PN","Renal outcomes defined in protocol. "]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"NA","Interim visits will occur as frequently as necessary in between scheduled protocol follow-up visits. They may be for measurements for evaluation of protocol safety issues (e.g. Action Items, laboratory tests) or held electively. These visits will help ensure that participant's assigned MAP goals are achieved or maintained by adjustment of antihypertensive agents."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalized cardiovascular events are reviewed and classified by a blinded endpoints committee according to a prespecified protocol."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The database shows all required results"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","The database shows all required results"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
[]
[]
["Unique ID",34,"Study ID","SPRINT","Assessor","JE"]
["Ref or Label","SPRINT 2015","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","total mortality","Results","RR=0.74","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","SPRINT will use an internet-based, web browser randomization procedure. "]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","No significant imbalance in the flow chart"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","No significant differences between groups"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","SAEs are adverse events that meet any of the following criteria: \u0095 fatal or life-threatening, \u0095 result in significant or persistent disability, \u0095 require or prolong hospitalization, \u0095 result in a congenital anomaly/birth defect, or \u0095 are important medical events that investigators judge to represent significant hazards or harm to research participants and may require medical or surgical intervention to prevent one of the other outcomes listed in this definition (e.g. hospitalization, death, persistent disability)."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","At each quarterly visit, SPRINT staff will specifically query participants for serious adverse events. In addition, information on serious adverse events may also be reported to study staff spontaneously by participants through telephone calls or emails between study visits. In addition to local reporting requirements, all serious adverse events will be recorded by clinic staff and forwarded to the CC Medical Safety Officer within 72 hours of knowledge of the event. SAEs will be collected and reported from screening to the end of the study follow-up period for an individual participant."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"NA","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits."]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",35,"Study ID","SPRINT","Assessor","JE"]
["Ref or Label","SPRINT 2015","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","total serious adverse events","Results","RR=0.97","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","SPRINT will use an internet-based, web browser randomization procedure. "]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","No significant imbalance in the flow chart"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","No significant differences between groups"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","SAEs are adverse events that meet any of the following criteria: \u0095 fatal or life-threatening, \u0095 result in significant or persistent disability, \u0095 require or prolong hospitalization, \u0095 result in a congenital anomaly/birth defect, or \u0095 are important medical events that investigators judge to represent significant hazards or harm to research participants and may require medical or surgical intervention to prevent one of the other outcomes listed in this definition (e.g. hospitalization, death, persistent disability)."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","At each quarterly visit, SPRINT staff will specifically query participants for serious adverse events. In addition, information on serious adverse events may also be reported to study staff spontaneously by participants through telephone calls or emails between study visits. In addition to local reporting requirements, all serious adverse events will be recorded by clinic staff and forwarded to the CC Medical Safety Officer within 72 hours of knowledge of the event. SAEs will be collected and reported from screening to the end of the study follow-up period for an individual participant."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"NA","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits."]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",36,"Study ID","SPRINT","Assessor","JE"]
["Ref or Label","SPRINT 2015","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","total cardiovascular events","Results","RR=0.83","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","SPRINT will use an internet-based, web browser randomization procedure. "]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","No significant imbalance in the flow chart"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","No significant differences between groups"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","SAEs are adverse events that meet any of the following criteria: \u0095 fatal or life-threatening, \u0095 result in significant or persistent disability, \u0095 require or prolong hospitalization, \u0095 result in a congenital anomaly/birth defect, or \u0095 are important medical events that investigators judge to represent significant hazards or harm to research participants and may require medical or surgical intervention to prevent one of the other outcomes listed in this definition (e.g. hospitalization, death, persistent disability)."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","At each quarterly visit, SPRINT staff will specifically query participants for serious adverse events. In addition, information on serious adverse events may also be reported to study staff spontaneously by participants through telephone calls or emails between study visits. In addition to local reporting requirements, all serious adverse events will be recorded by clinic staff and forwarded to the CC Medical Safety Officer within 72 hours of knowledge of the event. SAEs will be collected and reported from screening to the end of the study follow-up period for an individual participant."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"NA","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits."]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",37,"Study ID","SPRINT","Assessor","JE"]
["Ref or Label","SPRINT 2015","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","cardiovascular mortality","Results","RR=0.61","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","SPRINT will use an internet-based, web browser randomization procedure. "]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","No significant imbalance in the flow chart"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","No significant differences between groups"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","SAEs are adverse events that meet any of the following criteria: \u0095 fatal or life-threatening, \u0095 result in significant or persistent disability, \u0095 require or prolong hospitalization, \u0095 result in a congenital anomaly/birth defect, or \u0095 are important medical events that investigators judge to represent significant hazards or harm to research participants and may require medical or surgical intervention to prevent one of the other outcomes listed in this definition (e.g. hospitalization, death, persistent disability)."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","At each quarterly visit, SPRINT staff will specifically query participants for serious adverse events. In addition, information on serious adverse events may also be reported to study staff spontaneously by participants through telephone calls or emails between study visits. In addition to local reporting requirements, all serious adverse events will be recorded by clinic staff and forwarded to the CC Medical Safety Officer within 72 hours of knowledge of the event. SAEs will be collected and reported from screening to the end of the study follow-up period for an individual participant."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"NA","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits."]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",38,"Study ID","SPRINT","Assessor","JE"]
["Ref or Label","SPRINT 2015","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","kidney failure","Results","RR=0.59","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","SPRINT will use an internet-based, web browser randomization procedure. "]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","No significant imbalance in the flow chart"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","No significant differences between groups"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","SAEs are adverse events that meet any of the following criteria: \u0095 fatal or life-threatening, \u0095 result in significant or persistent disability, \u0095 require or prolong hospitalization, \u0095 result in a congenital anomaly/birth defect, or \u0095 are important medical events that investigators judge to represent significant hazards or harm to research participants and may require medical or surgical intervention to prevent one of the other outcomes listed in this definition (e.g. hospitalization, death, persistent disability)."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","At each quarterly visit, SPRINT staff will specifically query participants for serious adverse events. In addition, information on serious adverse events may also be reported to study staff spontaneously by participants through telephone calls or emails between study visits. In addition to local reporting requirements, all serious adverse events will be recorded by clinic staff and forwarded to the CC Medical Safety Officer within 72 hours of knowledge of the event. SAEs will be collected and reported from screening to the end of the study follow-up period for an individual participant."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"NA","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits."]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
[]
[]
["Unique ID",40,"Study ID","SPRINT","Assessor","JE"]
["Ref or Label","SPRINT 2015","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","Systolic blood pressure difference from baseline at one year","Results","MD=13.18","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","SPRINT will use an internet-based, web browser randomization procedure. "]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","No significant imbalance in the flow chart"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","No significant differences between groups"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","SAEs are adverse events that meet any of the following criteria: \u0095 fatal or life-threatening, \u0095 result in significant or persistent disability, \u0095 require or prolong hospitalization, \u0095 result in a congenital anomaly/birth defect, or \u0095 are important medical events that investigators judge to represent significant hazards or harm to research participants and may require medical or surgical intervention to prevent one of the other outcomes listed in this definition (e.g. hospitalization, death, persistent disability)."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","At each quarterly visit, SPRINT staff will specifically query participants for serious adverse events. In addition, information on serious adverse events may also be reported to study staff spontaneously by participants through telephone calls or emails between study visits. In addition to local reporting requirements, all serious adverse events will be recorded by clinic staff and forwarded to the CC Medical Safety Officer within 72 hours of knowledge of the event. SAEs will be collected and reported from screening to the end of the study follow-up period for an individual participant."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"NA","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits."]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",41,"Study ID","SPRINT","Assessor","JE"]
["Ref or Label","SPRINT 2015","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","Diastolic blood pressure difference from baseline at one year","Results","MD=7.42","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","SPRINT will use an internet-based, web browser randomization procedure. "]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","No significant imbalance in the flow chart"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","No significant differences between groups"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","SAEs are adverse events that meet any of the following criteria: \u0095 fatal or life-threatening, \u0095 result in significant or persistent disability, \u0095 require or prolong hospitalization, \u0095 result in a congenital anomaly/birth defect, or \u0095 are important medical events that investigators judge to represent significant hazards or harm to research participants and may require medical or surgical intervention to prevent one of the other outcomes listed in this definition (e.g. hospitalization, death, persistent disability)."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","At each quarterly visit, SPRINT staff will specifically query participants for serious adverse events. In addition, information on serious adverse events may also be reported to study staff spontaneously by participants through telephone calls or emails between study visits. In addition to local reporting requirements, all serious adverse events will be recorded by clinic staff and forwarded to the CC Medical Safety Officer within 72 hours of knowledge of the event. SAEs will be collected and reported from screening to the end of the study follow-up period for an individual participant."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"NA","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits."]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",42,"Study ID","SPRINT","Assessor","JE"]
["Ref or Label","SPRINT 2015","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","Doubling of serum creatinine level or 50% reduction in GFR at the end of study","Results","RR=0.90","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","SPRINT will use an internet-based, web browser randomization procedure. "]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","No significant imbalance in the flow chart"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","No significant differences between groups"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","SAEs are adverse events that meet any of the following criteria: \u0095 fatal or life-threatening, \u0095 result in significant or persistent disability, \u0095 require or prolong hospitalization, \u0095 result in a congenital anomaly/birth defect, or \u0095 are important medical events that investigators judge to represent significant hazards or harm to research participants and may require medical or surgical intervention to prevent one of the other outcomes listed in this definition (e.g. hospitalization, death, persistent disability)."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","At each quarterly visit, SPRINT staff will specifically query participants for serious adverse events. In addition, information on serious adverse events may also be reported to study staff spontaneously by participants through telephone calls or emails between study visits. In addition to local reporting requirements, all serious adverse events will be recorded by clinic staff and forwarded to the CC Medical Safety Officer within 72 hours of knowledge of the event. SAEs will be collected and reported from screening to the end of the study follow-up period for an individual participant."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"NA","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits."]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",43,"Study ID","SPRINT","Assessor","JE"]
["Ref or Label","SPRINT 2015","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","Proportion of participants reaching target levels of blood pressure at the end of study","Results","RR=0.88","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","SPRINT will use an internet-based, web browser randomization procedure. "]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","No significant imbalance in the flow chart"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","No significant differences between groups"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","SAEs are adverse events that meet any of the following criteria: \u0095 fatal or life-threatening, \u0095 result in significant or persistent disability, \u0095 require or prolong hospitalization, \u0095 result in a congenital anomaly/birth defect, or \u0095 are important medical events that investigators judge to represent significant hazards or harm to research participants and may require medical or surgical intervention to prevent one of the other outcomes listed in this definition (e.g. hospitalization, death, persistent disability)."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","At each quarterly visit, SPRINT staff will specifically query participants for serious adverse events. In addition, information on serious adverse events may also be reported to study staff spontaneously by participants through telephone calls or emails between study visits. In addition to local reporting requirements, all serious adverse events will be recorded by clinic staff and forwarded to the CC Medical Safety Officer within 72 hours of knowledge of the event. SAEs will be collected and reported from screening to the end of the study follow-up period for an individual participant."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"NA","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits."]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",44,"Study ID","SPRINT","Assessor","JE"]
["Ref or Label","SPRINT 2015","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","Number of antihypertensive drugs that each participant needed at the end of study","Results","MD=0.91","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","SPRINT will use an internet-based, web browser randomization procedure. "]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","No significant imbalance in the flow chart"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","No significant differences between groups"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","SAEs are adverse events that meet any of the following criteria: \u0095 fatal or life-threatening, \u0095 result in significant or persistent disability, \u0095 require or prolong hospitalization, \u0095 result in a congenital anomaly/birth defect, or \u0095 are important medical events that investigators judge to represent significant hazards or harm to research participants and may require medical or surgical intervention to prevent one of the other outcomes listed in this definition (e.g. hospitalization, death, persistent disability)."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","At each quarterly visit, SPRINT staff will specifically query participants for serious adverse events. In addition, information on serious adverse events may also be reported to study staff spontaneously by participants through telephone calls or emails between study visits. In addition to local reporting requirements, all serious adverse events will be recorded by clinic staff and forwarded to the CC Medical Safety Officer within 72 hours of knowledge of the event. SAEs will be collected and reported from screening to the end of the study follow-up period for an individual participant."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"NA","Participants and study personnel were aware of the study-group assignments, but outcome adjudicators were not."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","Both randomized groups will be assessed for study related outcomes in the same way and on the same schedule. After randomization, participants will be assessed every 3 months for cardiovascular and renal outcomes. Medical records will be collected for adjudication of study outcomes as described in Chapter 9. Clinical center staff will use available resources and contact information to assess vital status annually on participants not attending study visits."]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",45,"Study ID","SPS3","Assessor","JE"]
["Ref or Label","SPS3 2013","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","total mortality","Results","RR=0.96","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Following establishment of eligibility and obtaining informed consent, the SPS3 physician and research coordinator will complete baseline data forms at time of randomization. All patients will receive a kit of antiplatelet medications (aspirin plus either clopidogrel or placebo) bearing the randomization number, and all patients, regardless of hypertension status and blood pressure measurements will be randomized to one of the two target levels of BP control. Patients will not be randomized until two weeks after the qualifying stroke, thus BP lowering medications will not be adjusted by the SPS3 physician until at least two weeks following the stroke. Randomization will be stratified by hypertension status."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","The schedule was computer generated with a permuted-block design (variable block size). Treatment assignments were stored electronically on the study servers at the SPS3 statistical centre, University of Alabama at Birmingham, AL, USA, as well as locally for each study site on an SPS3-designated computer. Upon patients’ eligibility being established, study coordinators ransomised patients via their data entry systems."]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PY","No significant differences between groups"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Primary endpoint: First occurrence during follow-up of any stroke, including ischemic and hemorrhagic. Secondary endpoint: The impact of antiplatelet therapy on the rate of cognitive decline. Secondary endpoints were reductions in acute myocardial infarction, defined by standard criteria (compatible clinical history with changes on ECG or in cardiac enzyme concentrations), need for acute admission to hospital for a major vascular event, and death, classified as vascular, non-vascular, or unknown."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data."]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",46,"Study ID","SPS3","Assessor","JE"]
["Ref or Label","SPS3 2013","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","total serious adverse events","Results","RR=1.26","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Following establishment of eligibility and obtaining informed consent, the SPS3 physician and research coordinator will complete baseline data forms at time of randomization. All patients will receive a kit of antiplatelet medications (aspirin plus either clopidogrel or placebo) bearing the randomization number, and all patients, regardless of hypertension status and blood pressure measurements will be randomized to one of the two target levels of BP control. Patients will not be randomized until two weeks after the qualifying stroke, thus BP lowering medications will not be adjusted by the SPS3 physician until at least two weeks following the stroke. Randomization will be stratified by hypertension status."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","The schedule was computer generated with a permuted-block design (variable block size). Treatment assignments were stored electronically on the study servers at the SPS3 statistical centre, University of Alabama at Birmingham, AL, USA, as well as locally for each study site on an SPS3-designated computer. Upon patients’ eligibility being established, study coordinators ransomised patients via their data entry systems."]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PY","No significant differences between groups"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Primary endpoint: First occurrence during follow-up of any stroke, including ischemic and hemorrhagic. Secondary endpoint: The impact of antiplatelet therapy on the rate of cognitive decline. Secondary endpoints were reductions in acute myocardial infarction, defined by standard criteria (compatible clinical history with changes on ECG or in cardiac enzyme concentrations), need for acute admission to hospital for a major vascular event, and death, classified as vascular, non-vascular, or unknown."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data."]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",47,"Study ID","SPS3","Assessor","JE"]
["Ref or Label","SPS3 2013","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","total cardiovascular events","Results","RR=1.34","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Following establishment of eligibility and obtaining informed consent, the SPS3 physician and research coordinator will complete baseline data forms at time of randomization. All patients will receive a kit of antiplatelet medications (aspirin plus either clopidogrel or placebo) bearing the randomization number, and all patients, regardless of hypertension status and blood pressure measurements will be randomized to one of the two target levels of BP control. Patients will not be randomized until two weeks after the qualifying stroke, thus BP lowering medications will not be adjusted by the SPS3 physician until at least two weeks following the stroke. Randomization will be stratified by hypertension status."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","The schedule was computer generated with a permuted-block design (variable block size). Treatment assignments were stored electronically on the study servers at the SPS3 statistical centre, University of Alabama at Birmingham, AL, USA, as well as locally for each study site on an SPS3-designated computer. Upon patients’ eligibility being established, study coordinators ransomised patients via their data entry systems."]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PY","No significant differences between groups"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Primary endpoint: First occurrence during follow-up of any stroke, including ischemic and hemorrhagic. Secondary endpoint: The impact of antiplatelet therapy on the rate of cognitive decline. Secondary endpoints were reductions in acute myocardial infarction, defined by standard criteria (compatible clinical history with changes on ECG or in cardiac enzyme concentrations), need for acute admission to hospital for a major vascular event, and death, classified as vascular, non-vascular, or unknown."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data."]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",48,"Study ID","SPS3","Assessor","JE"]
["Ref or Label","SPS3 2013","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","cardiovascular mortality","Results","RR=0.87","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Following establishment of eligibility and obtaining informed consent, the SPS3 physician and research coordinator will complete baseline data forms at time of randomization. All patients will receive a kit of antiplatelet medications (aspirin plus either clopidogrel or placebo) bearing the randomization number, and all patients, regardless of hypertension status and blood pressure measurements will be randomized to one of the two target levels of BP control. Patients will not be randomized until two weeks after the qualifying stroke, thus BP lowering medications will not be adjusted by the SPS3 physician until at least two weeks following the stroke. Randomization will be stratified by hypertension status."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","The schedule was computer generated with a permuted-block design (variable block size). Treatment assignments were stored electronically on the study servers at the SPS3 statistical centre, University of Alabama at Birmingham, AL, USA, as well as locally for each study site on an SPS3-designated computer. Upon patients’ eligibility being established, study coordinators ransomised patients via their data entry systems."]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PY","No significant differences between groups"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Primary endpoint: First occurrence during follow-up of any stroke, including ischemic and hemorrhagic. Secondary endpoint: The impact of antiplatelet therapy on the rate of cognitive decline. Secondary endpoints were reductions in acute myocardial infarction, defined by standard criteria (compatible clinical history with changes on ECG or in cardiac enzyme concentrations), need for acute admission to hospital for a major vascular event, and death, classified as vascular, non-vascular, or unknown."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data."]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
[]
["Unique ID",51,"Study ID","SPS3","Assessor","JE"]
["Ref or Label","SPS3 2013","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","Systolic blood pressure difference from baseline at one year","Results","MD=8.00","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Following establishment of eligibility and obtaining informed consent, the SPS3 physician and research coordinator will complete baseline data forms at time of randomization. All patients will receive a kit of antiplatelet medications (aspirin plus either clopidogrel or placebo) bearing the randomization number, and all patients, regardless of hypertension status and blood pressure measurements will be randomized to one of the two target levels of BP control. Patients will not be randomized until two weeks after the qualifying stroke, thus BP lowering medications will not be adjusted by the SPS3 physician until at least two weeks following the stroke. Randomization will be stratified by hypertension status."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","The schedule was computer generated with a permuted-block design (variable block size). Treatment assignments were stored electronically on the study servers at the SPS3 statistical centre, University of Alabama at Birmingham, AL, USA, as well as locally for each study site on an SPS3-designated computer. Upon patients’ eligibility being established, study coordinators ransomised patients via their data entry systems."]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PY","No significant differences between groups"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Primary endpoint: First occurrence during follow-up of any stroke, including ischemic and hemorrhagic. Secondary endpoint: The impact of antiplatelet therapy on the rate of cognitive decline. Secondary endpoints were reductions in acute myocardial infarction, defined by standard criteria (compatible clinical history with changes on ECG or in cardiac enzyme concentrations), need for acute admission to hospital for a major vascular event, and death, classified as vascular, non-vascular, or unknown."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data."]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",52,"Study ID","SPS3","Assessor","JE"]
["Ref or Label","SPS3 2013","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","Diastolic blood pressure difference from baseline at one year","Results","MD=4.30","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Following establishment of eligibility and obtaining informed consent, the SPS3 physician and research coordinator will complete baseline data forms at time of randomization. All patients will receive a kit of antiplatelet medications (aspirin plus either clopidogrel or placebo) bearing the randomization number, and all patients, regardless of hypertension status and blood pressure measurements will be randomized to one of the two target levels of BP control. Patients will not be randomized until two weeks after the qualifying stroke, thus BP lowering medications will not be adjusted by the SPS3 physician until at least two weeks following the stroke. Randomization will be stratified by hypertension status."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","The schedule was computer generated with a permuted-block design (variable block size). Treatment assignments were stored electronically on the study servers at the SPS3 statistical centre, University of Alabama at Birmingham, AL, USA, as well as locally for each study site on an SPS3-designated computer. Upon patients’ eligibility being established, study coordinators ransomised patients via their data entry systems."]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PY","No significant differences between groups"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Primary endpoint: First occurrence during follow-up of any stroke, including ischemic and hemorrhagic. Secondary endpoint: The impact of antiplatelet therapy on the rate of cognitive decline. Secondary endpoints were reductions in acute myocardial infarction, defined by standard criteria (compatible clinical history with changes on ECG or in cardiac enzyme concentrations), need for acute admission to hospital for a major vascular event, and death, classified as vascular, non-vascular, or unknown."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data."]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
[]
[]
["Unique ID",54,"Study ID","SPS3","Assessor","JE"]
["Ref or Label","SPS3 2013","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","Proportion of participants reaching target levels of blood pressure at the end of study","Results","RR=1.30","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Following establishment of eligibility and obtaining informed consent, the SPS3 physician and research coordinator will complete baseline data forms at time of randomization. All patients will receive a kit of antiplatelet medications (aspirin plus either clopidogrel or placebo) bearing the randomization number, and all patients, regardless of hypertension status and blood pressure measurements will be randomized to one of the two target levels of BP control. Patients will not be randomized until two weeks after the qualifying stroke, thus BP lowering medications will not be adjusted by the SPS3 physician until at least two weeks following the stroke. Randomization will be stratified by hypertension status."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","The schedule was computer generated with a permuted-block design (variable block size). Treatment assignments were stored electronically on the study servers at the SPS3 statistical centre, University of Alabama at Birmingham, AL, USA, as well as locally for each study site on an SPS3-designated computer. Upon patients’ eligibility being established, study coordinators ransomised patients via their data entry systems."]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PY","No significant differences between groups"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Primary endpoint: First occurrence during follow-up of any stroke, including ischemic and hemorrhagic. Secondary endpoint: The impact of antiplatelet therapy on the rate of cognitive decline. Secondary endpoints were reductions in acute myocardial infarction, defined by standard criteria (compatible clinical history with changes on ECG or in cardiac enzyme concentrations), need for acute admission to hospital for a major vascular event, and death, classified as vascular, non-vascular, or unknown."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data."]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",55,"Study ID","SPS3","Assessor","JE"]
["Ref or Label","SPS3 2013","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","Number of antihypertensive drugs that each participant needed at the end of study","Results","MD=0.50","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Following establishment of eligibility and obtaining informed consent, the SPS3 physician and research coordinator will complete baseline data forms at time of randomization. All patients will receive a kit of antiplatelet medications (aspirin plus either clopidogrel or placebo) bearing the randomization number, and all patients, regardless of hypertension status and blood pressure measurements will be randomized to one of the two target levels of BP control. Patients will not be randomized until two weeks after the qualifying stroke, thus BP lowering medications will not be adjusted by the SPS3 physician until at least two weeks following the stroke. Randomization will be stratified by hypertension status."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","The schedule was computer generated with a permuted-block design (variable block size). Treatment assignments were stored electronically on the study servers at the SPS3 statistical centre, University of Alabama at Birmingham, AL, USA, as well as locally for each study site on an SPS3-designated computer. Upon patients’ eligibility being established, study coordinators ransomised patients via their data entry systems."]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PY","No significant differences between groups"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Primary endpoint: First occurrence during follow-up of any stroke, including ischemic and hemorrhagic. Secondary endpoint: The impact of antiplatelet therapy on the rate of cognitive decline. Secondary endpoints were reductions in acute myocardial infarction, defined by standard criteria (compatible clinical history with changes on ECG or in cardiac enzyme concentrations), need for acute admission to hospital for a major vascular event, and death, classified as vascular, non-vascular, or unknown."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"PN","Nine categories of events during follow up will require scrupulous standardized documentation and validation for correlation with the randomized interventions. All possible clinical stroke events (including suspected TIAs and syncopal spells of unclear cause) will be referred for blinded assessment by a board-certified neurologist. A standardized interview questionnaire to detect symptoms of TIA and stroke will be administered to all patients by the research coordinator at every quarterly follow up. Completed forms plus pertinent medical information (i.e. copies of medical records, reports of MRI, CT scans, etc. blinded to patient identification) will be reviewed by the Events Committee."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","Protocol, page 42-43. Only SAE related to hypotension and blood pressure management were reported. Despite repeated attempts to obtain clarification from the study authors, no response was received. At a later stage, all data were reviewed thanks to the National Institute of Neurologic Diseases and Stroke, which provided full access to individual patient data."]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"Some concerns"]
[]
[]
["Unique ID",56,"Study ID","MDRD","Assessor","JE"]
["Ref or Label","MDRD 1994","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","total mortality","Results","RR=1.35","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","The randomization schedules will be prepared by the Data Coordinating Center prior to the start of patient recruitment. Allocation to treatment groups will be equal. The specific allocation procedure will be a stratified block randomization procedure. The size of each block will be determined in a random fashion. The randomization process will be centrally administered. All randomization schedules will remain confidential and known only by members of the Data Coordinating Center staff. "]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PY","Eleven of the 585 patients in study 1 (1.9 percent) and 3 of the 255 in study 2 (1.2 percent) were lost to follow-up."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"PN","Effect variables defined in the protocol"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","Follow-up Procedures and Measurements. Protein intake was assessed monthly on the basis of 24-hour urinary excretion of urea nitrogen. Nitrogen in the prescribed keto acid-amino acid supplement was subtracted from urinary urea nitrogen. The intake of protein, calories, and other nutrients was assessed every two months on the basis of three-day dietary records. Blood pressure was measured monthly, and when necessary, adjustments in therapy were made monthly or more often. The glomerular filtration rate was measured at two months, at four months, and every four months thereafter on the basis of the renal clearance of [125I) iothalamate (Isotex Diagnostics, Friendswood, Tex.). Anthropometric measurements were obtained every four months."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"NI"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NI"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NI"]
[null,"Risk of bias judgement",null,null,"High"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The database shows all required results"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","Protocol and main article checked"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"High "]
[]
[]
["Unique ID",57,"Study ID","MDRD","Assessor","JE"]
["Ref or Label","MDRD 1994","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","total serious adverse events","Results","RR=1.12","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","The randomization schedules will be prepared by the Data Coordinating Center prior to the start of patient recruitment. Allocation to treatment groups will be equal. The specific allocation procedure will be a stratified block randomization procedure. The size of each block will be determined in a random fashion. The randomization process will be centrally administered. All randomization schedules will remain confidential and known only by members of the Data Coordinating Center staff. "]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PY","Eleven of the 585 patients in study 1 (1.9 percent) and 3 of the 255 in study 2 (1.2 percent) were lost to follow-up."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"PN","Effect variables defined in the protocol"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","Follow-up Procedures and Measurements. Protein intake was assessed monthly on the basis of 24-hour urinary excretion of urea nitrogen. Nitrogen in the prescribed keto acid-amino acid supplement was subtracted from urinary urea nitrogen. The intake of protein, calories, and other nutrients was assessed every two months on the basis of three-day dietary records. Blood pressure was measured monthly, and when necessary, adjustments in therapy were made monthly or more often. The glomerular filtration rate was measured at two months, at four months, and every four months thereafter on the basis of the renal clearance of [125I) iothalamate (Isotex Diagnostics, Friendswood, Tex.). Anthropometric measurements were obtained every four months."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"NI"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NI"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NI"]
[null,"Risk of bias judgement",null,null,"High "]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The database shows all required results"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","Protocol and main article checked"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"High "]
[]
[]
[]
[]
["Unique ID",59,"Study ID","MDRD","Assessor","JE"]
["Ref or Label","MDRD 1994","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","cardiovascular mortality","Results","RR=1.42","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","The randomization schedules will be prepared by the Data Coordinating Center prior to the start of patient recruitment. Allocation to treatment groups will be equal. The specific allocation procedure will be a stratified block randomization procedure. The size of each block will be determined in a random fashion. The randomization process will be centrally administered. All randomization schedules will remain confidential and known only by members of the Data Coordinating Center staff. "]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PY","Eleven of the 585 patients in study 1 (1.9 percent) and 3 of the 255 in study 2 (1.2 percent) were lost to follow-up."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"PN","Effect variables defined in the protocol"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","Follow-up Procedures and Measurements. Protein intake was assessed monthly on the basis of 24-hour urinary excretion of urea nitrogen. Nitrogen in the prescribed keto acid-amino acid supplement was subtracted from urinary urea nitrogen. The intake of protein, calories, and other nutrients was assessed every two months on the basis of three-day dietary records. Blood pressure was measured monthly, and when necessary, adjustments in therapy were made monthly or more often. The glomerular filtration rate was measured at two months, at four months, and every four months thereafter on the basis of the renal clearance of [125I) iothalamate (Isotex Diagnostics, Friendswood, Tex.). Anthropometric measurements were obtained every four months."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"NI"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NI"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NI"]
[null,"Risk of bias judgement",null,null,"High "]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The database shows all required results"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","Protocol and main article checked"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"High "]
[]
[]
["Unique ID",60,"Study ID","MDRD","Assessor","JE"]
["Ref or Label","MDRD 1994","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","kidney failure","Results","RR=0.98","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","The randomization schedules will be prepared by the Data Coordinating Center prior to the start of patient recruitment. Allocation to treatment groups will be equal. The specific allocation procedure will be a stratified block randomization procedure. The size of each block will be determined in a random fashion. The randomization process will be centrally administered. All randomization schedules will remain confidential and known only by members of the Data Coordinating Center staff. "]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PY","Eleven of the 585 patients in study 1 (1.9 percent) and 3 of the 255 in study 2 (1.2 percent) were lost to follow-up."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"PN","Effect variables defined in the protocol"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","Follow-up Procedures and Measurements. Protein intake was assessed monthly on the basis of 24-hour urinary excretion of urea nitrogen. Nitrogen in the prescribed keto acid-amino acid supplement was subtracted from urinary urea nitrogen. The intake of protein, calories, and other nutrients was assessed every two months on the basis of three-day dietary records. Blood pressure was measured monthly, and when necessary, adjustments in therapy were made monthly or more often. The glomerular filtration rate was measured at two months, at four months, and every four months thereafter on the basis of the renal clearance of [125I) iothalamate (Isotex Diagnostics, Friendswood, Tex.). Anthropometric measurements were obtained every four months."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"NA"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"High "]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The database shows all required results"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","Protocol and main article checked"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"High "]
[]
[]
[]
[]
["Unique ID",62,"Study ID","MDRD","Assessor","JE"]
["Ref or Label","MDRD 1994","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","Systolic blood pressure difference from baseline at one year","Results","MD=5.30","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","The randomization schedules will be prepared by the Data Coordinating Center prior to the start of patient recruitment. Allocation to treatment groups will be equal. The specific allocation procedure will be a stratified block randomization procedure. The size of each block will be determined in a random fashion. The randomization process will be centrally administered. All randomization schedules will remain confidential and known only by members of the Data Coordinating Center staff. "]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PY","Eleven of the 585 patients in study 1 (1.9 percent) and 3 of the 255 in study 2 (1.2 percent) were lost to follow-up."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"PN","Effect variables defined in the protocol"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","Follow-up Procedures and Measurements. Protein intake was assessed monthly on the basis of 24-hour urinary excretion of urea nitrogen. Nitrogen in the prescribed keto acid-amino acid supplement was subtracted from urinary urea nitrogen. The intake of protein, calories, and other nutrients was assessed every two months on the basis of three-day dietary records. Blood pressure was measured monthly, and when necessary, adjustments in therapy were made monthly or more often. The glomerular filtration rate was measured at two months, at four months, and every four months thereafter on the basis of the renal clearance of [125I) iothalamate (Isotex Diagnostics, Friendswood, Tex.). Anthropometric measurements were obtained every four months."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"NI"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NI"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NI"]
[null,"Risk of bias judgement",null,null,"High "]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The database shows all required results"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","Protocol and main article checked"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"High"]
[]
[]
["Unique ID",63,"Study ID","MDRD","Assessor","JE"]
["Ref or Label","MDRD 1994","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","Diastolic blood pressure difference from baseline at one year","Results","MD=4.00","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","The randomization schedules will be prepared by the Data Coordinating Center prior to the start of patient recruitment. Allocation to treatment groups will be equal. The specific allocation procedure will be a stratified block randomization procedure. The size of each block will be determined in a random fashion. The randomization process will be centrally administered. All randomization schedules will remain confidential and known only by members of the Data Coordinating Center staff. "]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PY","Eleven of the 585 patients in study 1 (1.9 percent) and 3 of the 255 in study 2 (1.2 percent) were lost to follow-up."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"PN","Effect variables defined in the protocol"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","Follow-up Procedures and Measurements. Protein intake was assessed monthly on the basis of 24-hour urinary excretion of urea nitrogen. Nitrogen in the prescribed keto acid-amino acid supplement was subtracted from urinary urea nitrogen. The intake of protein, calories, and other nutrients was assessed every two months on the basis of three-day dietary records. Blood pressure was measured monthly, and when necessary, adjustments in therapy were made monthly or more often. The glomerular filtration rate was measured at two months, at four months, and every four months thereafter on the basis of the renal clearance of [125I) iothalamate (Isotex Diagnostics, Friendswood, Tex.). Anthropometric measurements were obtained every four months."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"NI"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NI"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NI"]
[null,"Risk of bias judgement",null,null,"High "]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The database shows all required results"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","Protocol and main article checked"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"High "]
[]
[]
["Unique ID",64,"Study ID","MDRD","Assessor","JE"]
["Ref or Label","MDRD 1994","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","Doubling of serum creatinine level or 50% reduction in GFR at the end of study","Results","RR=0.67","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","The randomization schedules will be prepared by the Data Coordinating Center prior to the start of patient recruitment. Allocation to treatment groups will be equal. The specific allocation procedure will be a stratified block randomization procedure. The size of each block will be determined in a random fashion. The randomization process will be centrally administered. All randomization schedules will remain confidential and known only by members of the Data Coordinating Center staff. "]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PY","Eleven of the 585 patients in study 1 (1.9 percent) and 3 of the 255 in study 2 (1.2 percent) were lost to follow-up."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"PN","Effect variables defined in the protocol"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","Follow-up Procedures and Measurements. Protein intake was assessed monthly on the basis of 24-hour urinary excretion of urea nitrogen. Nitrogen in the prescribed keto acid-amino acid supplement was subtracted from urinary urea nitrogen. The intake of protein, calories, and other nutrients was assessed every two months on the basis of three-day dietary records. Blood pressure was measured monthly, and when necessary, adjustments in therapy were made monthly or more often. The glomerular filtration rate was measured at two months, at four months, and every four months thereafter on the basis of the renal clearance of [125I) iothalamate (Isotex Diagnostics, Friendswood, Tex.). Anthropometric measurements were obtained every four months."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"NI"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NI"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NI"]
[null,"Risk of bias judgement",null,null,"High "]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The database shows all required results"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","Protocol and main article checked"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"High "]
[]
[]
["Unique ID",65,"Study ID","MDRD","Assessor","JE"]
["Ref or Label","MDRD 1994","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Low targets","Comparator","Standard targets","Source"," Journal article(s); Trial protocol"]
["Outcome","Proportion of participants reaching target levels of blood pressure at the end of study","Results","RR=0.65","Weight",1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","The randomization schedules will be prepared by the Data Coordinating Center prior to the start of patient recruitment. Allocation to treatment groups will be equal. The specific allocation procedure will be a stratified block randomization procedure. The size of each block will be determined in a random fashion. The randomization process will be centrally administered. All randomization schedules will remain confidential and known only by members of the Data Coordinating Center staff. "]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","open trial"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NA"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","ITT analysis"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PY","Eleven of the 585 patients in study 1 (1.9 percent) and 3 of the 255 in study 2 (1.2 percent) were lost to follow-up."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"PN","Effect variables defined in the protocol"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","Follow-up Procedures and Measurements. Protein intake was assessed monthly on the basis of 24-hour urinary excretion of urea nitrogen. Nitrogen in the prescribed keto acid-amino acid supplement was subtracted from urinary urea nitrogen. The intake of protein, calories, and other nutrients was assessed every two months on the basis of three-day dietary records. Blood pressure was measured monthly, and when necessary, adjustments in therapy were made monthly or more often. The glomerular filtration rate was measured at two months, at four months, and every four months thereafter on the basis of the renal clearance of [125I) iothalamate (Isotex Diagnostics, Friendswood, Tex.). Anthropometric measurements were obtained every four months."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"NI"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NI"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NI"]
[null,"Risk of bias judgement",null,null,"High "]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The database shows all required results"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","Protocol and main article checked"]
[null,"Risk of bias judgement",null,null,"Low"]
["Overall bias","Risk of bias judgement",null,null,"High "]

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{"sheet":"Check","index":7,"n_rows":0,"n_cols":0,"rows_kept":0,"cut":false,"hidden":false,"merged":[]}

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["Unique ID",null,"Study ID",null,"Assessor"]
["Ref or Label",null,"Aim","adhering to intervention (the 'per-protocol' effect)","The effect of adhering to intervention…"]
["Experimental",null,"Comparator",null,"Source"]
["Outcome",null,"Results",null,"Weight"]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?"]
[null,"Risk of bias judgement"]
["Bias due to deviations from intended interventions","2.1 Were participants aware of their assigned intervention during the trial?"]
[null,"2.2 Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?"]
[null,"2.3. [If applicable:] If Y/PY/NI to 2.1 or 2.2: Were important non-protocol interventions balanced across intervention groups?"]
[null,"2.4. [If applicable:] Were there failures in implementing the intervention that could have affected the outcome?"]
[null,"2.5. [If applicable:] Was there non-adherence to the assigned intervention regimen that could have affected participants’ outcomes?"]
[null,"2.6. If N/PN/NI to 2.3, or Y/PY/NI to 2.4 or 2.5: Was an appropriate analysis used to estimate the effect of adhering to the intervention?"]
[null,"Risk of bias judgement"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?"]
[null,"Risk of bias judgement"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?"]
[null,"Risk of bias judgement"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?"]
[null,"5.3 ... multiple eligible analyses of the data?"]
[null,"Risk of bias judgement"]
["Overall bias","Risk of bias judgement"]

{"sheet":"Print_format (ITT)","index":9,"n_rows":33,"n_cols":6,"rows_kept":33,"cut":false,"hidden":true,"merged":[[19,1,19,3],[21,1,21,3],[32,1,32,3],[22,0,27,0],[22,1,22,3],[23,1,23,3],[27,1,27,3],[24,1,24,3],[25,1,25,3],[26,1,26,3],[30,1,30,3],[28,0,31,0],[28,1,28,3],[29,1,29,3],[31,1,31,3],[4,1,4,3],[9,0,16,0],[9,1,9,3],[13,1,13,3],[14,1,14,3],[16,1,16,3],[15,1,15,3],[19,5,20,5],[25,5,26,5],[5,0,8,0],[5,1,5,3],[5,5,6,5],[6,1,6,3],[7,1,7,3],[8,1,8,3],[9,5,10,5],[10,1,10,3],[11,1,11,3],[12,1,12,3],[20,1,20,3],[17,0,21,0],[17,1,17,3],[18,1,18,3]]}
["Unique ID",null,"Study ID",null,"Assessor"]
["Ref or Label",null,"Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental",null,"Comparator",null,"Source"]
["Outcome",null,"Results",null,"Weight"]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?"]
[null,"Risk of bias judgement"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?"]
[null,"Risk of bias judgement"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?"]
[null,"Risk of bias judgement"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?"]
[null,"Risk of bias judgement"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?"]
[null,"5.3 ... multiple eligible analyses of the data?"]
[null,"Risk of bias judgement"]
["Overall bias","Risk of bias judgement"]

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[null,"Journal article(s)","NA","Yes",null,"1.1 Was the allocation sequence random?",null,"2.1 Were participants aware of their assigned intervention during the trial?","2.1 Were participants aware of their assigned intervention during the trial?",null,"3.1 Were data for this outcome available for all, or nearly all, participants randomized?","Individually Randomized, Parallel Group Trials","4.1 Was the method of measuring the outcome inappropriate?","assignment to intervention (the 'intention-to-treat' effect)","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,null,"occurance of non-protocol interventions"]
["NA","Trial protocol","Favours experimental ","No (Please include reasons in the note)","Y","1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?","Low","2.2 Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?","2.2 Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,"3.2 If N/PN/NI to 3.1: Is there evidence that the result was not biased by missing outcome data?",null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?","adhering to intervention (the 'per-protocol' effect)","5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,null,"failures in implementing the intervention that could have affected the outcome"]
["Y","Statistical analysis plan (SAP)","Favours comparator ",null,"PY","1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?","High","2.3 [If applicable:] If Y/PY/NI to 2.1 or 2.2: Were important nonprotocol interventions balanced across intervention groups?","2.3 If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the trial context?",null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,"4.3 If N/PN/NI to 4.1 and 4.2: Were outcome assessors aware of the intervention received by study participants?",null,"5.3 ... multiple eligible analyses of the data?",null,null,null,"non-adherence to their assigned intervention by trial participants"]
["PY","Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Towards null ",null,"PN",null,"Some concerns","2.4 [If applicable:] Were there failures in implementing the intervention that could have affected the outcome?","2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?"]
["PN","Company-owned trial registry record (e.g. GSK Clinical Study Register record)","Away from null ",null,"N",null,null,"2.5 [If applicable:] Was there non-adherence to the assigned intervention regimen that could have affected participants’ outcomes?","2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?"]
["N","“Grey literature” (e.g. unpublished thesis)","Unpredictable",null,"NI",null,null,"2.6 If N/PN/NI to 2.3, or Y/PY/NI to 2.4 or 2.5: Was an appropriate analysis used to estimate the effect of adhering to the intervention?","2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?"]
["NI","Conference abstract(s) about the trial",null,null,null,null,null,null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?"]
[null,"Regulatory document (e.g. Clinical Study Report, Drug Approval Package)"]
[null,"Research ethics application"]
[null,"Grant database summary (e.g. NIH RePORTER, Research Councils UK Gateway to Research)"]
[null,"Personal communication with trialist"]
[null,"Personal communication with the sponsor"]