Table 1.
Criteria for assessing the quality of trials
| Score | Criteria | Impact on risk for bias |
|---|---|---|
| Randomisation and concealment | ||
| A | Randomisation: details of any adequate type of allocation method that generates random sequences with the patient as unit of randomisation are reported* Concealment: the trial provides evidence† that concealment was indeed effective and that the random sequence could not have been observed or predicted throughout the duration of the trial |
Doubt may still exist as to whether the trial results are influenced by selection bias, but no indication can be found from the trial report to support such doubt |
| B | Randomisation: details of any adequate type of allocation method that generates random sequences with the patient as unit of randomisation are reported* Concealment: the trial reports on any adequate method to prevent direct observation‡ and prediction§ of the allocation sequence and sequence generation rules |
Despite the implementation of a method considered able to prevent the unmasking of the concealed allocation sequence through direct observation and prediction, there are reasons to expect that the concealed allocation sequence may have been unmasked during the course of the trial |
| C | Randomisation: details of any adequate type of allocation method that generates random sequences with the patient as unit of randomisation are reported* Concealment: the trial reports on any adequate method to prevent direct operator observation of allocation sequence and sequence generation rules‡ However, the allocation sequence and sequence generation may have been sufficiently predicted |
Despite the implementation of a method considered able to prevent the unmasking of the concealed allocation sequence through direct observation, there are reasons to expect that operators could have predicted the concealed allocation sequence |
| D | Randomisation: details of any adequate type of allocation method that generates random sequences with the patient as unit of randomisation are reported* Concealment: the trial report does not include information on how the allocation of random sequence was concealed The allocation could have been directly observed and/or predicted |
Despite the theoretical chance for each patient to be allocated to either treatment group, operator knowledge of the allocation sequence may have led to patient allocation that favoured the outcome of one type of treatment over the other |
| 0 | The trial does not comply with criteria A–D | No guarantee of equal chance for patients to be allocated to either treatment group; thus allocation may have favoured the outcome of one type of treatment over the other |
| Baseline data for randomised trials | ||
| A | Baseline data collected before randomisation and reported for both treatment groups Data show no significant differences between groups |
Evidence is given that randomisation has led to equal groups, suggesting little risk for selection bias |
| B | Baseline data collected before randomisation and reported for both treatment groups Data show significant differences between groups but have been statistically adjusted appropriately |
Differences have been adjusted; thus the influence of possible selection bias appears to be reduced |
| C | Baseline data collected before randomisation and reported for both treatment groups Data show significant differences between the groups without being statistically adjusted |
Reported differences may reflect ineffective randomisation and thus indicate risk for selection bias |
| 0 | Trial does not comply with criteria A–C | No evidence is given on whether randomisation has indeed led to equal groups with differences beyond chance; thus differences may exist indicating selection bias |
| Blinding/masking | ||
| A | The trial reports on any type of method that is known to prevent the patient AND operator AND evaluator from discerning whether patients have been allocated to the test or control group (blinding/masking) The trial reports a process with which the effect of blinding/masking was evaluated, as well as the results of such evaluation |
Evidence is given that the trial results may not have been influenced by detection/performance bias that may have favoured the outcome of one type of treatment over the other |
| B | The trial reports on any type of method that is known to prevent the patient AND operator AND evaluator from discerning whether patients have been allocated to the test or control group (blinding/masking) The trial report does not give reason for doubt that patient allocation to either the test or control group has been unmasked throughout the duration of the trial |
Doubt may still exist as to whether the trial results are influenced by detection/performance bias, but no indication can be found in the trial report to support such doubt However, no evaluation of the blinding/masking effect has been included in the trial and thus no evidence for lack of bias is given |
| C | The trial reports on any type of method that is known to prevent the patient AND operator AND evaluator from discerning whether patients have been allocated to the test or control group (blinding/masking) The trial report gives reason for doubt that patient allocation to either the test or control group has been unmasked throughout the duration of the trial |
Despite the implementation of a method considered able to prevent unmasking, there are reasons to expect that operators or patients could have discovered the allocation |
| 0 | No process reported or implemented able to blind/mask patients AND operators as to whether patients were allocated to the test or control group (It is insufficient to report that blinding/masking occurred without reporting the details of the process) |
Knowledge about patient allocation may have caused patients or operators to act in a way that may have favoured the outcome of one type of treatment over the other |
| Loss to follow-up | ||
| A | Available case analysis, loss to follow-up reported per treatment group Subsequent sensitivity analysis does not indicate a possible risk for bias effect |
The trial allows the extraction of evidence that loss to follow-up has not favoured the outcome of one type of treatment over the other |
| B | Available case analysis, loss to follow-up reported per treatment group Subsequent sensitivity analysis indicates a possible risk for bias effect |
The trial allows the assessment of the risk that loss to follow-up may have favoured the outcome of one type of treatment over the other |
| 0 | The trial does not report the number of included participants per treatment group at baseline or give any indication that would allow the rate of loss to follow-up per treatment group to be ascertained | The trial carries an unknown risk that loss to follow-up may have favoured the outcome of one type of treatment over the other |
| Trial outcome | ||
| 0 | The trial reports on secondary or surrogate outcomes as endpoints | Even if the surrogate results would highly correlate with primary (i.e. clinical) outcomes, they cannot serve as valid replacements and should be considered for hypothesis development only |
| A | The trial reports on primary outcomes as endpoints | Primary outcomes may provide evidence for hypothesis testing |
*
Excluded are types of allocation methods that are considered inadequate, such as: cluster randomisation; fixed block randomisation with block size 2; minimisation; alternation; randomisation of teeth; use of date of birth or patient record number; ‘quasi’-randomisation, and split-mouth design.
†
For example, by reporting results of the Berger–Exner test or any other statistical tests that show that covariates of compared groups were similar at baseline.
‡
For example, by opening the opaque envelope, obtaining allocation from tables, by computer generation or from other sources.
§
For example, central randomisation, sequence allocation by other than operator; excluding varied block randomisation.