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["Basic information",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","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"]
["2020/12/11 11.36","rem","Consensus","Schreiber 2007","N Engl J Med 2007;357:239-50.","Certolizumab pegol","Placebo","Failure to maintain clinical remission at week 26","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Journal article(s) with results of the trial","PY","Y","Randomization was centralized by means of an interactive voice-recognization system with a computer-generated allocation sequence and ﻿the allocation sequence was adequately concealed.","N","No baseline differences that suggest a problem","Low","Low","The allocation sequence was adequately concealed and no baseline differences that suggest a problem with the randomisation process.",null,null,"N","N","Both participants and intervention were not awared","NA",null,"NA",null,"NA",null,"Y","All analyses were performed according to the intention-to-treat principle","NA",null,"Low","Low","Both participants and intervention were not aware and ITT analysis was performed",null,null,"PY","Two patients (1.0%) were loss to follow-up in experiment group (n=210) and one patient (0.5%) was loss to follow-up in comparator group (n=215)","NA",null,"NA",null,"NA",null,"Low","Low","Most participants were followed up; two patients (1.0%) were loss to follow-up in experiment group (n=210) and one patient (0.5%) was loss to follow-up in comparator group (n=215).",null,null,"N","Appropriate disease activity measurement (CDAI) was used","N","Consistent measurements were made for both intervention groups","N","Outcome assessors were not aware of the intervention","NA",null,"NA",null,"Low","Low","Appropriate disease activity measurement (CDAI) was used. Consistent measurements were made for both intervention groups. Outcome assessors were not aware of the intervention.",null,null,"Y","Published protocol with planned statistical method were performed","N","Reported measurement index and time point were appropriately predefined","N","Analyses were appropriately predefined","Low","Low","Published protocol with planned statistical method were performed. Reported measurement index and time point and analyses were appropriately predefined",null,null,"Low","Low","Due to low risk in all domains"]
["2020/12/10 22.38","res","Consensus","Schreiber 2007","N Engl J Med 2007;357:239-50.","Certolizumab pegol","Placebo","Failure to maintain clinical response at week 26","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Journal article(s) with results of the trial","PY","Y","Randomization was centralized by means of an interactive voice-recognization system with a computer-generated allocation sequence and ﻿the allocation sequence was adequately concealed.","N","No baseline differences that suggest a problem","Low","Low","The allocation sequence was adequately concealed and no baseline differences that suggest a problem with the randomisation process.",null,null,"N","N","Both participants and intervention were not awared","NA",null,"NA",null,"NA",null,"Y","All analyses were performed according to the intention-to-treat principle","NA",null,"Low","Low","Both participants and intervention were not aware and ITT analysis was performed",null,null,"PY","Two patients (1.0%) were loss to follow-up in experiment group (n=210) and one patient (0.5%) was loss to follow-up in comparator group (n=215)","NA",null,"NA",null,"NA",null,"Low","Low","Most participants were followed up; two patients (1.0%) were loss to follow-up in experiment group (n=210) and one patient (0.5%) was loss to follow-up in comparator group (n=215).",null,null,"N","Appropriate disease activity measurement (CDAI) was used","N","Consistent measurements were made for both intervention groups","N","Outcome assessors were not aware of the intervention","NA",null,"NA",null,"Low","Low","Appropriate disease activity measurement (CDAI) was used. Consistent measurements were made for both intervention groups. Outcome assessors were not aware of the intervention.",null,null,"Y","Published protocol with planned statistical method were performed","N","Reported measurement index and time point were appropriately predefined","N","Analyses were appropriately predefined","Low","Low","Published protocol with planned statistical method were performed. Reported measurement index and time point and analyses were appropriately predefined",null,null,"Low","Low","Due to low risk in all domains"]
["2020/12/11 16.47","adv","Consensus","Schreiber 2007","N Engl J Med 2007;357:239-50.","Certolizumab pegol","Placebo","Serious adverse events","assignment to intervention (the 'intention-to-treat' effect)","NA",1,"Journal article(s) with results of the trial","PY","Y","Randomization was centralized by means of an interactive voice-recognization system with a computer-generated allocation sequence ﻿and the allocation sequence was adequately concealed.","N","No baseline differences that suggest a problem","Low","Low","The allocation sequence was adequately concealed and no baseline differences that suggest a problem with the randomisation process.",null,null,"N","N","Both participants and intervention were not awared","NA",null,"NA",null,"NA",null,"Y","All analyses were performed according to the intention-to-treat principle","NA",null,"Low","Low","Both participants and intervention were not aware and ITT analysis was performed",null,null,"PY","Two patients (1.0%) were loss to follow-up in experiment group (n=212) and one patient (0.5%) was loss to follow-up in comparator group (n=216)","NA",null,"NA",null,"NA",null,"Low","Low","Most participants were followed up; two patients (1.0%) were loss to follow-up in experiment group (n=212) and one patient (0.5%) was loss to follow-up in comparator group (n=216).",null,null,"PN","There was no detail information of measurement instrument, but the measured outcomes were consistent with a series of PRECISE trials.","N","Consistent measurements were made for both intervention groups","N","Outcome assessors were not aware of the intervention","NA",null,"NA",null,"Low","Low","There was no detail information of measurement instrument, but the measured outcomes were consistent with a series of PRECISE trials. Consistent measurements were made for both intervention groups. The outcome assessors were not aware of the intervention.",null,null,"PY","There was no detail information of pre-specified analysis, but the measured outcomes were consistent with a series of PRECISE trials.","PN","Analysis intentions were not reported in sufficient, but the measured outcomes were consistent with a series of PRECISE trials.","PN","Analysis intentions were not reported in sufficient, but the measured outcomes were consistent with a series of PRECISE trials.","Low","Low","There was no detail information of pre-specified analysis and analysis intentions, but the measured outcomes were consistent with a series of PRECISE trials.",null,null,"Low","Low","Due to low risk in all domains"]

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["Basic information",null,null,null,"Domain 1. Randomization process",null,"Domain 2. Deviations from intended interventions",null,"Domain 3. Mising outcome data",null,null,"Domain 4. Measurement of the outcome",null,null,"Domain 5. Selection of the reported result",null,"Domain 6. Overall Bias"]
["Study ID","Experimental","Comparator","Outcome","1.0 Algorithm result","1.0 Assessor's Judgement","2.0 Algorithm result","2.0 Assessor's Judgement","Note for 3.4 (not use)","3.0 Algorithm result","3.0 Assessor's judgement","Note for 4.5 (not use)","4.0 Algorithm result","4.0 Assessor's Judgement","5.0 Algorithm result","5.0 Assessor's Judgement","Algorithm's overall Judgement","Assessor's overall Judgement"]
["Schreiber 2007","Certolizumab pegol","Placebo","Failure to maintain clinical remission at week 26","Low","Low","Low","Low",null,"Low","Low",null,"Low","Low","Low","Low","Low","Low"]
["Schreiber 2007","Certolizumab pegol","Placebo","Failure to maintain clinical response at week 26","Low","Low","Low","Low",null,"Low","Low",null,"Low","Low","Low","Low","Low","Low"]
["Schreiber 2007","Certolizumab pegol","Placebo","Serious adverse events","Low","Low","Low","Low",null,"Low","Low",null,"Low","Low","Low","Low","Low","Low"]

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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"]

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["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) with results of the trial","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 non- protocol 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 experimental 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, UKRI Gateway to Research)"]
[null,"Personal communication with trialist"]
[null,"Personal communication with the sponsor"]