Criteria for a judgment of ‘yes’ for the sources of bias

1. Was the allocation sequence randomly generated?
Yes, low risk of bias
A random (unpredictable) assignment sequence.
Examples of adequate methods of sequence generation are computer‐generated random sequence, pre‐ordered sealed envelopes, telephone call to a central office, coin toss (for studies with two groups), rolling a dice (for studies with two or more groups), drawing of balls of different colours.
No, high risk of bias
‐ Quasi‐randomized approach: Examples of inadequate methods are: alternation, birth date, social insurance/security number, date in which they are invited to participate in the study, and hospital registration number
‐ Non‐random approaches: Allocation by judgement of the clinician; by preference of the participant; based on the results of a laboratory test or a series of tests; by availability of the intervention.
Unclear
Insufficient information about the sequence generation process to permit judgement

2. Was the treatment allocation adequately concealed?
Yes, low risk of bias
Assignment must be generated independently by a person not responsible for determining the eligibility of the participants. This person has no information about the persons included in the trial and has no influence on the assignment sequence or on the decision about whether the person is eligible to enter the trial. Examples of adequate methods of allocation concealment are: Central allocation, including telephone, web‐based, and pharmacy controlled,randomization; sequentially numbered drug containers of identical appearance; sequentially numbered, opaque, sealed envelopes.
No, high risk of bias
Examples of inadequate methods of allocation concealment are: alternate medical record numbers, unsealed envelopes; date of birth; case record number; alternation or rotation; an open list of random numbers any information in the study that indicated that investigators or participants could influence the intervention group.
Unclear
Randomization stated but no information on method of allocation used is available.

3. Blinding was knowledge of the allocated interventions adequately prevented during the study?
Was the participant blinded to the intervention?
Yes, low risk of bias
The treatment and control groups are indistinguishable for the participants or if the participant was described as blinded and the method of blinding was described.
No, high risk of bias
‐ Blinding of study participants attempted, but likely that the blinding could have been broken; participants were not blinded, and the nonblinding of others likely to introduce bias.
Unclear

Was the care provider blinded to the intervention?
Yes, low risk of bias
The treatment and control groups are indistinguishable for the care/treatment providers or if the care provider was described as blinded and the method of blinding was described.
No, high risk of bias
Blinding of care/treatment providers attempted, but likely that the blinding could have been broken; care/treatment providers were not blinded, and the nonblinding of others likely to introduce bias.
Unclear

Was the outcome assessor blinded to the intervention?
Yes, low risk of bias
Adequacy of blinding should be assessed for the primary outcomes. The outcome assessor was described as blinded and the method of blinding was described.
No, high risk of bias
No blinding or incomplete blinding, and the outcome or outcome measurement is likely to be influenced by lack of blinding
Unclear

4. Were incomplete outcome data adequately addressed?
Was the drop‐out rate described and acceptable?
The number of participants who were included in the study but did not complete the observation period or were not included in the analysis must be described and reasons given.
Yes, low risk of bias
If the percentage of withdrawals and drop‐outs does not exceed 20% for short‐term follow‐up and 30% for long‐term follow‐up and does not lead to substantial bias. (N.B. these percentages are arbitrary, not supported by literature);
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;
Missing data have been imputed using appropriate methods.
No, high risk of bias
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;
Unclear

Were all randomized participants analysed in the group to which they were allocated? (ITT analysis)
Yes, low risk of bias
Specifically reported by authors that ITT was undertaken and this was confirmed on study assessment, or not stated but evident from study assessment that all randomized participants are reported/analysed in the group they were allocated to for the most important time point of outcome measurement (minus missing values) irrespective of non‐compliance and co‐interventions.
No, high risk of bias
Lack of ITT confirmed on study assessment (patients who were randomized were not included in the analysis because they did not receive the study intervention, they withdrew from the study or were not included because of protocol violation) regardless of whether ITT reported or not
‘As‐treated’ analysis done with substantial departure of the intervention received from that assigned at randomization; potentially inappropriate application of simple imputation.
Unclear
Described as ITT analysis, but unable to confirm on study assessment, or not reported and unable to confirm by study assessment.

5. Are reports of the study free of suggestion of selective outcome reporting?
Yes, low risk of bias
If all the results from all pre‐specified outcomes have been adequately reported in the published report of the trial. This information is either obtained by comparing the protocol and the final trial report, or in the absence of the protocol, assessing that the published report includes enough information to make this judgment. Alternatively a judgement could be made if the trial report lists the outcomes of interest in the methods of the trial and then reports all these outcomes in the results section of the trial report.
No, high risk of bias
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 prespecified;
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

6. Other sources of potential bias:
Were the groups similar at baseline regarding the most important prognostic indicators?
Groups have to be similar at baseline regarding demographic factors, duration and severity of complaints, for example size and duration of wound. Alternatively if there were imbalances at baseline these have been accounted for in the analysis of the study.

Were co‐interventions avoided or similar?
There were no co‐interventions or there were co‐interventions but they were similar between the treatment and control groups.

Was the compliance acceptable in all groups?
The review author determines if the compliance with the interventions is acceptable, based on the reported intensity, duration, number and frequency of sessions for both the treatment intervention and control intervention(s). For example, ultrasound treatment is usually administered over several sessions; therefore it is necessary to assess how many sessions each participant attended or if participants completed the course of an oral drug therapy. For single‐session interventions (for example: surgery), this item is irrelevant.

Was the timing of the outcome assessment similar in all groups?
Timing of outcome assessment should be identical for all intervention groups and for all important outcome assessments.

Was the trial sponsored by a manufacturer who potentially had an interest in the results?
Trials that state they received funding from a manufacturer or company with a direct interest in the intervention or trialists funded or employed by a manufacturer or company with a direct interest in the intervention.