Item	Judgement	Description
Random sequence generation (selection bias)	Low risk	Investigators describe a random component in the sequence generation process such as random numbers table; computer random number generator; coin tossing; shuffling cards or envelopes; throwing dice; drawing of lots; minimisation.
	High risk	Investigators describe a non‐random component in the sequence generation process such as odd or even date of birth; date (or day) of admission; hospital or clinic record number; alternation; judgement of the clinician; results of a laboratory test or a series of tests; availability of the intervention.
	Unclear risk	Information about the sequence generation process was insufficient to permit judgement of low or high risk.
Allocation concealment (selection bias)	Low risk	Investigators enrolling participants could not foresee assignment because one of the following, or an equivalent method, was used to conceal allocation: central allocation (including telephone, web‐based and pharmacy‐controlled randomisation); sequentially numbered drug containers of identical appearance; sequentially numbered, opaque, sealed envelopes.
	High risk	Investigators enrolling participants could possibly foresee assignments because one of the following method was used: open random allocation schedule (e.g. a list of random numbers); assignment envelopes without appropriate safeguards (e.g. envelopes were unsealed or were non‐opaque or were not sequentially numbered); alternation or rotation; date of birth; case record number; any other explicitly unconcealed procedure.
	Unclear risk	Information was insufficient to permit judgement of low or high risk. This is usually the case if the method of concealment is not described or is not described in sufficient detail to allow a definitive judgement.
Blinding of participants and personnel (performance bias)	Low risk	No blinding or incomplete blinding, but review authors judge that the outcome is not likely to be influenced by lack of blinding; or blinding of participants and key study personnel ensured, and unlikely that blinding could have been broken
	High risk	No blinding or incomplete blinding, and the outcome is likely to be influenced by lack of blinding; or blinding of key study participants and personnel attempted, but likely that blinding could have been broken, and the outcome is likely to be influenced by lack of blinding
	Unclear risk	Information was insufficient to permit judgement of low or high risk
Blinding of outcome assessment (detection bias) ‐ objective outcomes	Low risk	No blinding of outcome assessment, but review authors judge that the outcome measurement is not likely to be influenced by lack of blinding; or blinding of outcome assessment ensured and unlikely that blinding could have been broken
	High risk	No blinding of outcome assessment, and the outcome measurement is likely to be influenced by lack of blinding; or blinding of outcome assessment, but likely that blinding could have been broken and the outcome measurement is likely to be influenced by lack of blinding
	Unclear risk	Information was insufficient to permit judgement of low or high risk.
Incomplete outcome data (attrition bias). For all outcomes except retention in treatment or dropout	Low risk	No missing outcome data; or percentage of missing data ≤ 10% of the overall sample and (1) reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing bias), (2) missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups, (3) for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk not enough to have a clinically relevant impact on the intervention effect estimate and (4) for continuous outcome data, plausible effect size (difference in means or standardised difference in means) among missing outcomes not enough to have a clinically relevant impact on observed effect size; or missing data > 10% but (1) they have been imputed using appropriate methods, or (2) all randomised participants are reported/analysed in the group to which they were allocated by randomisation irrespective of non‐compliance and co‐interventions (intention to treat)
	High risk	Percentage of missing data > 10% or missing data unbalanced across groups; or reason for missing outcome data likely to be related to true outcome, with imbalance in numbers or reasons for missing data across intervention groups; or, for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce clinically relevant bias in intervention effect estimate; or, for continuous outcome data, plausible effect size (difference in means or standardised difference in means) among missing outcomes enough to induce clinically relevant bias in observed effect size; or ‘as‐treated’ analysis done with substantial departure of the intervention received from that assigned at randomisation
	Unclear risk	Information insufficient to permit judgement of low or high risk (e.g. number randomised not stated, no reasons for missing data provided; number of dropouts not reported for each group)
Selective outcome reporting (reporting bias)	Low risk	The study protocol is available, and all of the study’s prespecified (primary and secondary) outcomes that are of interest in the review have been reported in the prespecified way; or the study protocol is not available but all study outcomes declared in the Methods section were reported in the Results
	High risk	Not all of the study’s prespecified primary outcomes have been reported; or ≥ 1 primary outcome is reported using measurements, analysis methods or subsets of the data (e.g. subscales) that were not prespecified; or ≥ 1 reported primary outcome was not prespecified (unless clear justification for their reporting is provided, such as an unexpected adverse effect); or ≥ 1 outcome of interest in the review is reported incompletely, so cannot be entered into a meta‐analysis; or the study report fails to include results for a key outcome that would be expected to have been reported for such a study
	Unclear risk	Information insufficient to permit judgement of low or high risk
Other bias	Low risk	The study appeared to be free of other sources of bias such as being stopped early because of a data‐dependent process or having a baseline imbalance between groups. For cross‐over studies, we assessed if a washout period ≥ 1 day was provided.
	High risk	Baseline imbalance among groups; or no washout period for cross‐over studies
	Unclear risk	Information insufficient to permit judgement of low or high risk; study authors contacted for clarification, but the information was not forthcoming