Table 2.

RoB 2 guidelines on risk of bias assessment

Bias arising from the randomisation process
Low risk of bias	(i.) The allocation sequence was adequately concealed
	AND
	(ii.1) any baseline differences observed between intervention groups appear to be compatible with chance
	OR
	(ii.2) there is no information about baseline imbalances
	AND
	(iii.1) the allocation sequence was random
	OR
	(iii.2) there is no information about whether the allocation sequence was random
Some concerns	(i.1) The allocation sequence was adequately concealed
	AND
	(i.2.1) the allocation sequence was not random
	OR
	(i.2.2) baseline differences between intervention groups suggest a problem with the randomisation process
	OR
	(ii.1) there is no information about concealment of the allocation
	AND
	(ii.2) any baseline differences observed between intervention groups appear to be compatible with chance
	OR
	(iii) there is no information to answer any of the signalling questions
High risk of bias	(i.) The allocation sequence was not adequately concealed
	OR
	(ii.1) there is no information about concealment of the allocation sequence
	AND
	(ii.2) baseline differences between intervention groups suggest a problem with the randomisation process
Bias due to deviation from intended interventions
Low risk of bias	(i.1) Participants, carers and people delivering the interventions were unaware of intervention groups during the trial
	OR
	(i.2.1) participants, carers or people delivering the interventions were aware of intervention groups
	AND
	(i.2.2) [if applicable] the important non-protocol interventions were balanced across intervention groups
	AND (ii) [if applicable] failures in implementing the intervention could not have affected the outcome
	AND
	(iii) [if applicable] study participants adhered to the assigned intervention regimen.
Some concerns	(i.1.1) Participants, carers and people delivering the interventions were unaware of intervention groups during the trial
	AND
	(i.1.2.1) [if applicable] failures in implementing the intervention could have affected the outcome
	OR
	(i.1.2.2) [if applicable] study participants did not adhere to the assigned intervention regimen
	OR
	(i.2.1) participants, carers or people delivering the interventions were aware of intervention groups and (i.2.2) [if applicable] the important non-protocol interventions were balanced across intervention groups
	AND
	(i.2.3.1) [if applicable] failures in implementing the intervention could have affected the outcome
	OR
	(i.2.3.2) [if applicable] study participants did not adhere to the assigned intervention regimen
	OR
	(i.3.1) participants, carers or people delivering the interventions were aware of intervention groups
	AND
	(i.3.2) [if applicable] the important non-protocol interventions were not balanced across intervention groups
	AND
	(ii) an appropriate analysis was used to estimate the effect of adhering to intervention.
High risk of bias	(i.1.1) Participants, carers and people delivering the interventions were unaware of intervention groups during the trial
	AND
	(i.1.2.1) [if applicable] failures in implementing the intervention could have affected the outcome
	OR
	(i.1.2.2) [if applicable] study participants did not adhere to the assigned intervention regimen
	OR
	(i.2.1) participants, carers or people delivering the interventions were aware of intervention groups
	AND
	(i.2.2) [if applicable] the important non-protocol interventions were balanced across intervention groups
	AND
	(i.2.3.1) [if applicable] failures in implementing the intervention could have affected the outcome
	OR
	(i.2.3.2) [if applicable] study participants did not adhere to the assigned intervention regimen
	OR
	(i.3.1) participants, carers or people delivering the interventions were aware of intervention groups
	AND
	(i.3.2) [if applicable] the important non-protocol interventions were not balanced across intervention groups
	AND
	(ii) an appropriate analysis was not used to estimate the effect of adhering to intervention
Bias due to missing outcome data
Low risk of bias	(i.) Outcome data were available for all, or nearly all, randomised participants
	OR
	(ii.) there is evidence that the result was not biased by missing outcome data
	OR
	(iii) missingness in the outcome could not depend on its true value.
Some concerns	(i.) Outcome data were not available for all, or nearly all, randomized participants
	AND
	(ii.) there is not evidence that the result was not biased by missing outcome data
	AND
	(iii.) missingness in the outcome could depend on its true value
	AND
	(iv) it is not likely that missingness in the outcome depended on its true value.
High risk of bias	(i.) Outcome data were not available for all, or nearly all, randomized participants
	AND
	(ii.) there is not evidence that the result was not biased by missing outcome data
	AND
	missingness in the outcome could depend on its true value
	AND
	(iv) it is likely that missingness in the outcome depended on its true value
Bias in measurement of outcomes
Low risk of bias	(i.) The method of measuring the outcome was not inappropriate
	AND
	(ii.) the measurement or ascertainment of the outcome did not differ between intervention groups
	AND
	(iii.1) the outcome assessors were unaware of the intervention received by study participants
	OR
	(iii.2) the assessment of the outcome could not have been influenced by knowledge of the intervention received.
Some concerns	(i.1) The method of measuring the outcome was not inappropriate
	AND
	(i.2) the measurement or ascertainment of the outcome did not differ between intervention groups
	AND
	(i.3) the assessment of the outcome could have been influenced by knowledge of the intervention received
	AND
	(i.4) it is unlikely that assessment of the outcome was influenced by knowledge of intervention received
	OR
	(ii.1) the method of measuring the outcome was not inappropriate
	AND
	(ii.2) there is no information on whether the measurement or ascertainment of the outcome could have differed between intervention groups
	AND
	(ii.3.1) the outcome assessors were unaware of the intervention received by study participants
	OR
	(ii.3.2) the assessment of the outcome could not have been influenced by knowledge of the intervention received.
High risk of bias	(i.) The method of measuring the outcome was inappropriate
	OR
	(ii.) the measurement or ascertainment of the outcome could have differed between intervention groups
	OR
	(iii) it is likely that assessment of the outcome was influenced by knowledge of the intervention received
Bias arising from selective reporting of results
Low risk of bias	(i.) The data were analysed in accordance with a pre-specified plan that was finalised before unblinded outcome data were available for analysis
	AND
	(ii) the result being assessed is unlikely to have been selected, on the basis of the results, from multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain
	AND
	(iii) reported outcome data are unlikely to have been selected, on the basis of the results, from multiple eligible analyses of the data
Some concerns	(i.1) The data were not analysed in accordance with a pre-specified plan that was finalised before unblinded outcome data were available for analysis
	AND
	(i.2) the result being assessed is unlikely to have been selected, on the basis of t he results, from multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain
	AND
	(i.3) the result being assessed is unlikely to have been selected, on the basis of the results, from multiple eligible analyses of the data
	OR
	(ii) there is no information on whether the result being assessed is likely to have been selected, on the basis of the results, from multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain and from multiple eligible analyses of the data.
High risk of bias	(i.) The result being assessed is likely to have been selected, on the basis of the results, from multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain
	OR
	(ii) the result being assessed is likely to have been selected, on the basis of the results, from multiple eligible analyses of the data