Table 1.

Criteria used to assess risk of bias in included studies

Trials assessed as having “low risk of bias” in all the specified individual domains were considered “trials with low risk of bias”. Trials assessed as having “uncertain risk of bias” or “high risk of bias” in one or more of the specified individual domains were considered “trials with high risk of bias”.

Allocation sequence generation

Low risk of bias: sequence generation was achieved using computer random number generation or a random number table. Drawing lots, tossing a coin, shuffling cards and throwing dice are adequate if performed by an independent adjudicator.

Unclear risk of bias: the trial is described as randomized, but the method of sequence generation was not specified.

High risk of bias: the sequence generation method is not, or may not be, random. Quasi-randomized studies, those using dates, names or admittance numbers in order to allocate patients are inadequate and will be excluded for the assessment of benefits, but not for harms.

Allocation concealment

Low risk of bias: allocation was controlled by a central and independent randomization unit, sequentially numbered, opaque and sealed envelopes or similar, so that intervention allocations could not have been foreseen in advance of, or during, enrolment.

Unclear risk of bias: the trial was described as randomized, but the method used to conceal the allocation was not described, so that intervention allocations might have been foreseen in advance of, or during, enrolment.

High risk of bias: if the allocation sequence was known to the investigators who assigned patients or if the study was quasi-randomized. Quasirandomized studies will be excluded for the assessment of benefits, but not for harms.

Blinding

Low risk of bias: the trial was described as blinded, the parties that were blinded, and the method of blinding was described, so that knowledge of allocation was adequately prevented during the trial.

Unclear risk of bias: the trial was described as blind, but the method of blinding was not described, so that knowledge of allocation was possible during the trial.

High risk of bias, the trial was not blinded, so that the allocation was known during the trial.

Incomplete outcome data

Low risk of bias: the numbers and reasons for dropouts and withdrawals in all intervention groups were described or if it was specified that there were no dropouts or withdrawals.

Unclear risk of bias: the report gave the impression that there had been no dropouts or withdrawals, but this was not specifically stated.

High risk of bias: the number or reasons for dropouts and withdrawals were not described.

Selective outcome reporting

Low risk of bias: pre-defined, or clinically relevant and reasonably expected outcomes are reported on.

Unclear risk of bias: not all pre-defined, or clinically relevant and reasonably expected outcomes are reported on or are not reported fully, or it is unclear whether data on these outcomes were recorded or not.

High risk of bias: one or more clinically relevant and reasonably expected outcomes were not reported on; data on these outcomes were likely to have been recorded.

Other bias

Low risk of bias: the trial appears to be free of other components that could increase risk of bias.

Unclear risk of bias: the trial may or may not be free of other components that could increase risk of bias.

High risk of bias: there are other factors in the trial that could increase risk of bias (eg, for-profit involvement, authors have conducted trials on the same topic).