Item

Judgement

Description

1. Random sequence generation (selection bias)

Low risk

Investigators describe 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

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 series of tests; availability of the intervention

Unclear risk

Insufficient information about the sequence generation process to permit judgement of low or high risk

2. Allocation concealment (selection bias)

Low risk

Investigators enrolling participants could not foresee assignment because 1 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 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. envelopes were unsealed or non­opaque or were 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 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

3. Blinding of participants and providers (performance bias)

Low risk

No blinding or incomplete blinding, but the review authors judge that the outcome is not likely to be influenced by lack of blinding;

blinding of participants and key study personnel was ensured, and it was 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 was attempted, but it is likely that the 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

4. Blinding of outcome assessors (detection bias)

Low risk

No blinding of outcome assessment, but the review authors judge that the outcome measurement is not likely to be influenced by lack of blinding;

blinding of outcome assessment was ensured, and it is unlikely that the blinding could have been broken

High risk

No blinding of outcome assessment, and outcome measurement is likely to be influenced by lack of blinding;

blinding of outcome assessment, but it is likely that the 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

5. Incomplete outcome data (attrition bias)

for all outcomes except retention in treatment or dropout

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 was not enough to have a clinically relevant impact on the intervention effect estimate

For continuous outcome data, the plausible effect size (difference in means or standardised difference in means) among missing outcomes was not enough to have a clinically relevant impact on observed effect size

Missing data have been imputed using appropriate methods

All randomly assigned participants were reported/analysed in the group to which they were allocated 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 imbalance in numbers or reasons for missing data across intervention groups

For dichotomous outcome data, the proportion of missing outcomes compared with observed event risk was 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 was enough to induce clinically relevant bias in observed effect size

‘As‐treated’ analysis was done with substantial departure of the intervention received from that assigned at randomisation

Unclear risk

Information was insufficient to permit judgement of low or high risk (e.g. number randomly assigned not stated, no reasons for missing data provided; number of dropouts not reported for each group)

6. Selective 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 for this review have been reported in the prespecified way

The study protocol is not available, but it is clear that published reports include 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 have been reported

One or more primary outcomes are reported using measurements, analysis methods or subsets of data (e.g. subscales) that were not prespecified

One or more reported primary outcomes were not prespecified (unless clear justification for their reporting is provided, such as an unexpected adverse effect)

One or more outcomes of interest in the review are reported incompletely so that they cannot be entered into a meta‐analysis

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 was insufficient to permit judgement of low or high risk