No.	Item	Judgement	Description
1	Random sequence generation (selection bias)	Low risk	The investigators described a random component in the sequence generation process such as: random‐number table; computer random‐number generator; coin tossing; shuffling cards or envelopes; throwing dice; drawing of lots; minimisation.
		High risk	The investigators described 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; preference of the participant; results of a laboratory test or a series of tests; availability of the intervention.
		Unclear risk	Insufficient information about the sequence generation process to permit judgement of 'low risk' or 'high risk'.
2	Allocation concealment (selection bias)	Low risk	Investigators enrolling participants could not have foreseen assignment because 1 of the following, or an equivalent method, was used to conceal allocation: central allocation (including telephone, Internet‐based, and pharmacy‐controlled randomisation); sequentially numbered drug containers of identical appearance; sequentially numbered, opaque, sealed envelopes.
		High risk	Investigators enrolling participants could possibly have foreseen assignments and thus introduced selection bias because 1 of the following methods was used: open random allocation schedule (e.g. a list of random numbers); assignment envelopes without appropriate safeguards (e.g. if envelopes were unsealed or non‐opaque or not sequentially numbered); alternation or rotation; date of birth; case record number; any other explicitly unconcealed procedure.
		Unclear risk	Insufficient information to permit judgement of 'low risk' or 'high risk'. This is usually the case if the method of concealment was not described or not described in sufficient detail to allow a definite judgement.
3	Blinding of participants and providers (performance bias) Objective outcomes	Low risk	No blinding or incomplete blinding, but the review authors judged that the outcome was not likely to have been influenced by lack of blinding; blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.
		High risk	No blinding or incomplete blinding, and the outcome was likely to be influenced by lack of blinding; blinding of key study participants and personnel attempted, but likely that the blinding could have been broken, and the outcome was likely to be influenced by lack of blinding.
		Unclear risk	Insufficient information to permit judgement of 'low risk' or 'high risk'; the study did not address this outcome.
4	Blinding of participants and providers (performance bias) Subjective outcomes	Low risk	Blinding of participants and providers ensured, and unlikely that the blinding could have been broken
		High risk	No blinding or incomplete blinding, and the outcome is likely to be influenced by lack of blinding; blinding of key study participants and personnel attempted, but likely that the blinding could have been broken, and the outcome is likely to be influenced by lack of blinding,
		Unclear risk	Insufficient information to permit judgement of 'low risk' or 'high risk'; the study did not address this outcome.
5	Blinding of outcome assessor (detection bias) Objective outcomes	Low risk	No blinding of outcome assessment, but the review authors judged that the outcome measurement was not likely to be influenced by lack of blinding; blinding of outcome assessment ensured, and unlikely that the blinding could have been broken.
		High risk	No blinding of outcome assessment, and the outcome measurement was likely to be influenced by lack of blinding; blinding of outcome assessment, but likely that the blinding could have been broken, and the outcome measurement was likely to be influenced by lack of blinding.
		Unclear risk	Insufficient information to permit judgement of 'low risk' or 'high risk'; the study did not address this outcome.
6	Blinding of outcome assessor (detection bias) Subjective outcomes	Low risk	Blinding of outcome assessment ensured, and unlikely that the blinding could have been broken.
		High risk	No blinding of outcome assessment, and the outcome measurement was likely to be influenced by lack of blinding; blinding of outcome assessment, but likely that the blinding could have been broken, and the outcome measurement was likely to be influenced by lack of blinding.
		Unclear risk	Insufficient information to permit judgement of 'low risk' or 'high risk'; the study did not address this outcome.
7	Incomplete outcome data (attrition bias) For all outcomes except retention in treatment	Low risk	No missing outcome data; reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing bias); missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups; 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; 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; missing data had been imputed using appropriate methods; all randomised participants were reported/analysed in the group they were allocated to by randomisation, irrespective of non‐compliance and co‐interventions (intention‐to‐treat).
		High risk	Reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across interventions groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce clinically relevant bias in intervention effect estimate; 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; 'as‐treated' analysis done with substantial departure of the intervention received from that assigned at randomisation.
		Unclear risk	Insufficient reporting of attrition/exclusions to permit judgement of 'low risk' or 'high risk' (e.g. number randomised not stated, no reasons for missing data provided; the study did not address this outcome).
8	Selective reporting (reporting bias)	Low risk	The study protocol was available and all of the study's prespecified (primary and secondary) outcomes that were of interest in the review were reported in the prespecified way; the study protocol was not available but it was clear that the published reports included all expected outcomes, including those that were prespecified (convincing text of this nature may be uncommon)
		High risk	Not all of the study's prespecified primary outcomes were reported; ≥ 1 primary outcomes was reported using measurements, analysis methods, or subsets of the data (e.g. subscales) that were not prespecified; ≥ 1 reported primary outcomes were not prespecified (unless clear justification for their reporting was provided, such as an unexpected adverse effect); ≥ 1 outcomes of interest in the review were reported incompletely so that they could not be entered in a meta‐analysis; the study report failed to include results for a key outcome that would be expected to have been reported for such a study.
		Unclear risk	Insufficient information to permit judgement of 'low risk' or 'high risk'.
9	Other sources of bias	Low risk	The study appeared free of other sources of bias.
		High risk	There was ≥ 1 important risk of bias; e.g. the study had a potential source of bias related to the specific study design used; or had been claimed to have been fraudulent; or had some other problem.
		Unclear risk	There may be a risk of bias, but there was either: insufficient information to assess whether an important risk of bias existed; or insufficient rationale or evidence that an identified problem would introduce bias.