Table 1 Summary of ROBINS-I tool

Review protocol level considerations

Specify aspects of review question: Population, Intervention, Comparator, Outcome (PICO).

Outline how complexities in the PICO will be accommodated in the review.

Confounders: the review protocol should pre-specify relevant confounders which are related to exposure to the intervention.

Co-interventions: the review protocol should state interventions or exposures which are related to the intervention and prognostic for the outcome of interest.

Study level considerations (to be assessed for each study)

Target trial (TT): define key characteristics (eligibility of participants, intervention, comparator, outcome, effect of interest (see below)) of a hypothetical RCT (this should not be limited by pragmatic or ethical concerns).

Effect of interest (EoI): per protocol (PP—starting and adhering to intervention as outlined in intervention protocol) OR intention to treat (ITT—assignment to receive intervention regardless of subsequent exposure or adherence)

Bias domains

Pre-intervention

Domain 1: confounding

Domain 2: selection of participants into the study

At intervention

Domain 3: classification of interventions

Post-intervention

Domain 4: deviation from intended interventions*

Domain 5: missing data*

Domain 6: measurement of outcomes*

Domain 7: selection of reported result*

* Domain also part of RoB version 2.0 for RCTs

Assessment options for each signalling question (SQ): Yes, Probably Yes, Probably No, No, No Information.

Domain level RoB assessment options: Low, Moderate, Serious, Critical, No information.

Overall assessment (by outcome): Low, Moderate, Serious, Critical.