The quality of randomised trials of tocolysis

Tocolytic treatment of suspected preterm labour has been evaluated in at least 75 randomised controlled trials. These have been included in six Cochrane reviews. If the trials are poorly designed, such reviews may mislead or, at best, provide weaker evidence than those based on well-designed ones. The objective of this study was to compare the quality of the trials included in the Cochrane reviews of tocolytic therapy. Trial group sizes; the methods used by each trial to avoid selection, performance, attrition, and detection bias; and evidence that the statistical analysis plan was prespecified were abstracted from each Cochrane review. Except where noted, the judgement of the Cochrane reviewers was used. The number of trials graded A (sealed envelopes or third-party randomisation) for allocation concealment was as follows: beta-agonists 5/16, magnesium sulphate 9/23, oxytocin receptor antagonists 6/6, cox inhibitors 12/13, calcium channel blockers 9/12, and nitric oxide donors 5/5. The number blinding the intervention was as follows: beta-agonists 9/16, magnesium sulphate 2/23, oxytocin receptor antagonists 5/6, cox inhibitors 7/13, calcium channel blockers 0/12, and nitric oxide donors 1/5. The number reporting a sample size calculation was as follows: beta-agonists 2/16, magnesium sulphate 3/23, oxytocin receptor antagonists 6/6, cox inhibitors 4/13, calcium channel blockers 4/12, and nitric oxide donors 1/5. The mean sample size of each treatment group was as follows: beta-agonists 53, magnesium sulphate 41, oxytocin receptor antagonists 126, cox inhibitors 31, calcium channel blockers 43, and nitric oxide donors 46. Data on avoiding attrition bias (follow-up rates) are difficult to summarise because there is no agreed standard for 'complete follow up'. Data on avoiding detection bias (blinding of outcome assessments) appeared unreliable because reviewers reported this in different ways. In conclusion, the trials of oxytocin antagonists and beta-agonists were of the highest quality. There remains considerable scope for bias in many of the trials included in the current Cochrane systematic reviews of tocolytics.