Assessment of risk of bias in included studies

Two authors (SM and NOC) will independently assess risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions,²² with any disagreements resolved by discussion. In cases where consensus cannot be achieved, the trial will be assessed by a third reviewer (AR) for arbitration and a majority decision will be made.

We will assess the following for each study:

Random sequence generation (checking for possible selection bias). We will assess the method used to generate the allocation sequence as: low risk of bias (any truly random process, eg, random number table; computer random number generator); unclear risk of bias (method used to generate sequence not clearly stated); high risk of bias (studies using a non-random process, eg, odd or even date of birth; hospital or clinic record number).

Allocation concealment (checking for possible selection bias). The method used to conceal allocation to group prior to assignment determines whether intervention allocation could have been foreseen in advance of, or during recruitment, or changed after assignment. We will assess the methods as: low risk of bias (eg, telephone or central randomisation; consecutively numbered sealed opaque envelopes); unclear risk of bias (method not clearly stated); high risk of bias (studies that do not conceal allocation, eg, open list).

Blinding of participants: low risk of bias (participants blinded to allocated intervention; and unlikely that blinding is broken); unclear risk of bias (insufficient information to permit judgement of low/high risk of bias); high risk of bias (patients not blinded to allocated intervention OR patients blinded to allocated intervention but it is likely that blinding may have been broken (and a given outcome is likely to be influenced by lack of blinding)).

Blinding of care providers: low risk of bias (care provider blinded to allocated intervention; and unlikely that blinding is broken OR no/incomplete blinding but judged that a given outcome is unlikely to be influenced by lack of blinding); unclear risk of bias (insufficient information to permit judgement of low/high risk of bias); high risk of bias (care provider not blinded to allocated intervention and the two interventions clearly identifiable to the care provider as experimental and control OR care provider blinded to allocated intervention but likely that blinding may have been broken (and a given outcome is likely to be influenced by lack of blinding)).

Blinding of assessor: low risk of bias (outcome assessor (including patients with respect to self-report outcomes) blinded to patients allocated intervention; and unlikely that blinding is broken, or no/incomplete blinding but judged that a given outcome is unlikely to be influenced by lack of blinding); unclear risk of bias (insufficient information to permit judgement of low/high risk of bias); high risk of bias (outcome assessor (including patients with respect to self-report outcomes) unblinded to patients allocated intervention OR outcome assessor blinded to allocated intervention but likely that blinding may have been broken (and a given outcome is likely to be influenced by lack of blinding)).

We will first check for possible attrition bias by considering if participant dropout rate is appropriately described and acceptable. Low: if less than 20% dropout and appears to be missing at random. Numbers given per group and reasons for dropout described. Unclear: if less than 20% but reasons not described and numbers per group not given. Unclear that data are missing at random. High: if over 20% even if imputed appropriately.

We will separately consider if participants were analysed in the group to which they were allocated. Low: if analysed data in group to which they were originally assigned (be that with appropriately imputed data or an available case analysis). Unclear: insufficient information provided to determine if analysis was per protocol or intention to treat. High: if per-protocol analysis was used. Where available data were not analysed or participant’s data were included in group they were not originally assigned to.

We will assess whether studies are free of the suggestion of selective outcome reporting. Methods will be assessed as: low risk of bias (study protocol available and all prespecified outcomes of interest adequately reported. Study protocol not available but all expected outcomes of interest adequately reported. All primary outcomes numerically reported with point estimates and measures of variance for all time points); high risk of bias (incomplete reporting of prespecified outcomes. One or more primary outcomes are reported using measurements, analysis methods or subsets of data that were not prespecified. One or more reported primary outcomes were not prespecified. One or more outcomes of interest reported incompletely and cannot be entered into a meta-analysis. Results for a key outcome expected to have been reported excluded).

We will consider other risk factors such as whether trials were stopped early, differences between groups at baseline, timing of outcome assessment, control of cointerventions and author source of funding declarations.