Domain	Review authors'judgement*	Description	Page/ Para/ Figure #
Was the allocation sequence adequately generated?	Yes / No / Unclear	Describe the method used to generate the allocation sequence in sufficient detail to allow an assessment of whether it should produce comparable groups.
Was allocation adequately concealed?	Yes / No / Unclear	Describe the method used to conceal the allocation sequence in sufficient detail to determine whether intervention allocations could have been foreseen in advance of, or during, enrolment.
Were baseline outcome measurements similar?	Yes/No/Unclear	Note whether baseline outcome measurements were reported and whether there were any important differences between groups. If there were important differences between groups, note whether appropriate adjusted analysis was performed to account for this.
Were baseline characteristics similar?	Yes/No/Unclear	Note whether baseline characteristics were reported and whether there were any important differences between groups.
Were incomplete outcome data adequately addressed? Assessments should be made for each main outcome (or class of outcomes).	Yes / No / Unclear	Describe the completeness of outcome data for each main outcome, including attrition and exclusions from the analysis. State whether attrition and exclusions were reported, the numbers in each intervention group (compared with total randomized participants), reasons for attrition/exclusions where reported, and any re‐inclusions in analyses performed by the review authors.
Was knowledge of the allocated intervention adequately prevented during the study? Separate assessments should be made for relevant groups of people involved in the study i.e. participants, outcome assessors, investigators, data assessors etc	Yes / No / Unclear	Describe all measures used, if any, to blind study participants and personnel from knowledge of which intervention a participant received. Provide any information relating to whether the intended blinding was effective, or whether blinding was appropriate. · Participants – yes, no, unclear [record supporting statement from study]. · Investigators – yes, no, unclear [record supporting statement from study]. · Outcomes assessors – yes, no, unclear [record supporting statement from study]. Data assessors – yes, no, unclear [record supporting statement from study].
Was the study adequately protected against contamination?	Yes/No/Unclear	State whether and how the possibility of contamination was minimised by the study design/implementation.
Are reports of the study free of suggestion of selective outcome reporting? Assessments should be made for each main outcome (or class of outcomes).	Yes / No / Unclear	State how the possibility of selective outcome reporting was examined by the review authors, and what was found.
Other sources of bias ·	Yes / No / Unclear	State any important concerns about bias not addressed in the other domains in the tool.
ITS: Was the intervention independent of other changes?	Yes/No/Unclear	Describe whether or not the intervention occurred independently of other changes over time and whether or not the outcomes may have been influenced by other confounding variables/historic events during the study period.
ITS: Was the shape of the intervention effect pre‐specified?	Yes/No/Unclear	State whether or not the point of analysis was the point of intervention. If not, describe whether a rationale for the shape of the intervention effect was given by the study authors.
ITS: Was the intervention unlikely to affect data collection?	Yes/No/Unclear	Describe whether or not the intervention was likely to affect data collection and what the potential impact might have been.
ITS: Was knowledge of the allocated interventions adequately prevented during the study? Separate assessments should be made for relevant groups of people involved in the study i.e. participants, outcome assessors, investigators, data assessors etc	Yes/No/Unclear	Describe all measures used, if any, to blind study participants and personnel from knowledge of which intervention a participant received. Provide any information relating to whether the intended blinding was effective, or whether blinding was appropriate. · Participants – yes, no, unclear [record supporting statement from study]. · Investigators – yes, no, unclear [record supporting statement from study]. · Outcomes assessors – yes, no, unclear [record supporting statement from study]. Data assessors – yes, no, unclear [record supporting statement from study].
ITS: Was incomplete outcome data adequately addressed? Assessments should be made for each main outcome (or class of outcomes).	Yes/No/Unclear	Describe the completeness of outcome data for each main outcome, including attrition and exclusions from the analysis. State whether attrition and exclusions were reported, the numbers in each intervention group (compared with total randomized participants), reasons for attrition/exclusions where reported, and any re‐inclusions in analyses performed by the review authors.
ITS: Was the study free from selective reporting?	Yes/No/Unclear	State how the possibility of selective outcome reporting was examined by the review authors, and what was found.
ITS: Was the study free from other risks of bias?	Yes/No/Unclear	State any important concerns about bias not addressed in the other domains in the tool.