Item

 Judgment

 Description

1. Random sequence generation (selection bias)

Low risk

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

High risk

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 risk

Insufficient information about the sequence generation process to permit judgement of low or high risk

2. Allocation concealment (selection bias)

Low risk

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, randomisation); sequentially numbered drug containers of identical appearance; sequentially numbered, opaque, sealed envelopes.

High risk

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 non­opaque or not sequentially numbered); alternation or rotation; date of birth; case record number; any other explicitly unconcealed procedure.

Unclear risk

Insufficient information to permit judgement of low or high risk 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. Blinding of participants and providers (performance bias)

Objective outcomes 

Low risk

No blinding or incomplete blinding, but the review authors judge that the outcome is not likely to be influenced by lack of blinding;

Blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.

4. Blinding of participants and providers (performance bias)

Subjective outcomes

Low risk

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

High risk

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

Unclear risk

Insufficient information to permit judgement of low or high risk;

5. Blinding of outcome assessor (detection bias)

Objective outcomes 

Low risk

No blinding of outcome assessment, but the review authors judge that the outcome measurement is not likely to be influenced by lack of blinding;

Blinding of outcome assessment ensured, and unlikely that the blinding could have been broken

6.Blinding of outcome assessor (detection  bias)

Subjective outcomes

Low risk

No blinding of outcome assessment, but the review authors judge that the outcome measurement is not likely to be influenced by lack of blinding;

Blinding of outcome assessment ensured, and unlikely that the blinding could have been broken

High risk

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

Blinding of outcome assessment, but likely that the blinding could have been broken, and the outcome measurement is likely to be influenced by lack of blinding

Unclear risk

Insufficient information to permit judgement of low or high risk;

7. Incomplete outcome data (attrition bias)

For all outcomes except retention in treatment or drop out

Low risk

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 randomised patients are reported/analysed in the group they were allocated to by randomisation irrespective of non‐compliance and co‐interventions (intention to treat)

High risk

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 randomisation; 

Unclear risk

Insufficient information to permit judgement of low or high risk (e.g. number randomised not stated, no reasons for missing data provided; number of drop out not reported for each group);

8. Selective reporting (reporting bias)

Low risk

The study protocol is available and all of the study’s pre‐specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre‐specified way;

The study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre‐specified (convincing text of this nature may be uncommon).

High risk

Not all of the study’s pre‐specified primary outcomes have been reported;

One or more primary outcomes is reported using measurements, analysis methods or subsets of the data (e.g. subscales) that were not pre‐specified;

One or more reported primary outcomes were not pre‐specified (unless clear justification for their reporting is provided, such as an unexpected adverse effect);

One or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta‐analysis;

The study report fails to include results for a key outcome that would be expected to have been reported for such a study.

Unclear risk

Insufficient information to permit judgement of low or high risk