Item

Judgment

Description

1

Was the method of randomization adequate?

Yes

The 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; minimization

No

The 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 a series of tests;  availability of the intervention

Unclear

Insufficient information about the sequence generation process to permit judgement of ‘Yes’ or ‘No’.

2

Was the treatment allocation concealed?

Yes

Investigators enrolling participants could not foresee assignment because one of the following, or an equivalent method, was used to conceal allocation: central allocation (including telephone, web‐based, and pharmacy‐controlled, randomization); sequentially numbered drug containers of identical appearance; sequentially numbered, opaque, sealed envelopes.

No

Investigators enrolling participants could possibly foresee assignments because one of the following method was used: open random allocation schedule (e.g. a list of random numbers); assignment envelopes without appropriate safeguards (e.g. if envelopes were unsealed or non ­opaque or not sequentially numbered); alternation or rotation; date of birth; case record number; any other explicitly unconcealed procedure.

Unclear

Insufficient information to permit judgement of ‘Yes’ or ‘No’. This is usually the case if the method of concealment is not described or not described in sufficient detail to allow a definite judgement

3/4

Was knowledge of the allocated interventions adequately prevented during the study? (blinding of patients, provider, outcome assessor)

Objective outcomes

Subjective outcomes

Yes

Blinding of participants, providers and outcome assessor and unlikely that the blinding could have been broken;

Either participants or providers were not blinded, but outcome assessment was blinded and the non‐blinding of others unlikely to introduce bias.

No blinding, but the objective  outcome measurement are not likely to be influenced by lack of blinding

No

No blinding or incomplete blinding, and the outcome or outcome measurement is likely to be influenced by lack of blinding;

Blinding of key study participants and personnel attempted, but likely that the blinding could have been broken;

Either participants or outcome assessor were not blinded, and the non‐blinding of others likely to introduce bias

Unclear

Insufficient information to permit judgement of ‘Yes’ or ‘No’;

5

Were incomplete outcome data adequately addressed?

For all outcomes except retention in treatment or drop out

Yes

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

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

Missing data have been imputed using appropriate methods

All randomized patients are reported/analyzed in the group they were allocated to by randomization irrespective of non‐compliance and co‐interventions (intention to treat)

No

Reason for missing outcome data likely to be related to true outcome, with either 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 enough to induce clinically relevant bias in intervention effect estimate;

For continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes enough to induce clinically relevant bias in observed effect size;

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

Unclear

Insufficient reporting of attrition/exclusions to permit judgement of ‘Yes’ or ‘No’ (e.g. number randomized not stated, no reasons for missing data provided; number of drop out not reported for each group);