Quality Assurance Editors in Cochrane Central Editorial Service use the questions below to assess the methods of submitted protocols for intervention reviews. We make these questions freely available so you can check your work before you submit.

This is the checklist for protocols. Go to the methods peer review checklist for reviews and updates.

The assessment questions follow the structure of headings and subheadings in RevMan. For further information on preparing your manuscript for submission, see Check your work meets our standards.

Background

• Is there a clearly defined rationale for why it is important to do this review?
• Are the objectives, eligibility criteria, and PICO clear and logical from the background?

Methods

Types of studies

• Are eligible trial designs stated and justified? (e.g., define quasi-randomised, e.g., "randomised by day of week". Assume that unless otherwise stated, cluster RCT, cross over studies, and multi arms studies are eligible. If not, must be specified and justified here)

Types of participants

• Are participants clearly defined, for example, criteria around location, setting, diagnoses or definition of condition and demographic factors?
• Is there a plan for including studies with a subset of eligible participants?

Types of interventions

• Are interventions clearly defined, including mandatory components?
• Are active and inactive comparators adequately described?
• Are dose, frequency, duration and other aspects of the intervention adequately described?

Outcome measures

• Are the most important outcomes selected (ideally no more than 7) and categorized as critical and important? Do these outcomes include benefits and harms?
• Are outcomes adequately described? E.g. units, scales, timeframes, primary time point.
• Is there a hierarchy of which scale will be extracted if a study measures more than one scale for a given outcome?
• Will studies be included regardless of outcomes reported? If excluded based on outcomes reported, is appropriate rationale presented?

Selection of studies

• Are two people working independently on selecting studies, with a plan for resolving disagreements, and for contacting trial authors?
• While not mandatory at protocol stage, it is helpful if authors provide the initials of authors who will complete these tasks, to demonstrate how they will do this independently.

Data extraction and management

• Are two people working independently to extract outcome data, with a plan for resolving disagreements?
• Will the data extraction form be piloted?

Risk of bias assessment in included studies

• Are two people working independently at all stages of risk of bias assessment, with a plan for resolving disagreements, and for contacting trial authors?
• Is Cochrane RoB tool sufficiently described? Do any changes in domain have clear, robust justification?
• Is it appropriate to assess outcomes differently? If so, have authors considered this? E.g. patient reported vs physician reported.
• If non-randomised studies are eligible for inclusion, have all ROBINS-I (or similar tool for NRSI studies) guidance points been adhered to?

Additional questions for reviews using Risk of bias 2

• Assessment of risk of bias in included studies
  • Is the RoB2 tool stated and referenced?
  • Have the authors stated the effect of interest (assignment or adherence)?
  • Have the authors listed results which will be assessed using RoB2 including outcomes, outcome measures, and time points?
  • Will at least two authors independently assess RoB2 (with initials)?
• Cluster RCTs and cross-over RCTs
  • Have authors described methods for considering RoB in cluster RCTs and cross-over RCTs as per the interim guidance?

Measures of treatment effect

• Have the authors stated the effect measures that will be used for continuous data (E.g., MD, SMD) and dichotomous data (RR, OR, RD, etc)?
• If any of the outcomes could be reported as time to event data, have the authors considered how they will handle this data (e.g., using Hazard Ratios?)

Unit of analysis

• Are the following considered (if appropriate to review question)?
  • Cross-over trials?
  • Cluster trials?
  • Multiple arm studies?
  • Split-body designs (only if applicable to research question)?

Dealing with missing data

• Is there an appropriate plan for missing data?

Reporting biases assessment

• Is there an appropriate plan for assessment of reporting biases? (e.g., use of funnel plots, but only if there are more than 10 studies in an analysis)?

Synthesis methods

• Have authors specified their comparisons of interest in this review? Is the scope of this review ’manageable’? Have authors planned for the smallest number of comparisons that address the main objectives?
• Will meta-analysis be conducted only if there is sufficient similarity in studies?
• Has fixed / random effects been declared in advance?
• If Fixed Effect Model is to be used, ensure authors have stated the method they will use (such as Mantel-Haenszel, or Inverse-variance)
• If Random Effects Model is to be used;  
  • Will authors calculate heterogeneity using DL or REML (REML is the recommended approach)?  
  • Will authors calculate the summary mean confidence interval using Wald or HKSJ (decision will depend on tau2 value and number of studies)?  
  • Do authors plan to present a confidence interval for the heterogeneity value? (optional!)  
  • Do authors plan to present a prediction interval? (optional!)
• Have authors described intended methods for synthesizing studies without meta-analysis?

Investigation of heterogeneity and subgroup analyses

• Have authors described how heterogeneity will be assessed? Consider statistical heterogeneity, clinical heterogeneity and methodology heterogeneity?
• Are subgroup analyses pre-defined and justified? (These should relate to the background and PICO and be kept to a minimum (i.e. 3-5)
• Will subgroups be assessed using the formal Test for Subgroup Differences in RevMan?

Equity-related assessment

• Have the review authors considered issues of equity, and planned for appropriate methods to address them if they are?
• If equity related assessment is not to be conducted, is this stated and justified?

Sensitivity analysis

• Are sensitivity analyses clearly defined and appropriate?

Certainty of evidence assessment

• Is there a clear plan to present only the most important comparisons included in the SoF table? Ensure one table per comparison.
• Are the most important outcomes (max 7) to be included in the SoF table pre-specified and consistently worded?
• Are adverse effects included?
• Have authors specified which time points and method of measurement will be prioritised for each outcome?
• Are two people working independently to assess the certainty of the body of evidence with a plan for resolving disagreements?
• Are GRADE considerations clearly described and appropriately referenced?

Patient and public involvement

• If patients and/or public are involved, have authors reported specific details and methods (their level of involvement, general approach, roles ,stage and any formal research methods or techniques to be used)?
• Have authors included a supplemental file to describe the planned involvement of patients/public?
• If patients and/or public were not involved, is this stated and justified?

Conflicts of interest

• Are any authors cited in the background section, as this could mean they are authors of included studies?

Supplementary materials

• Are there are details provided in main text that should be a 'supplementary material'?
• Are there any 'supplementary materials' that could be a reference within the text?