Multicentre randomised trials in anaesthesia: an analysis using Bayesian metrics.

Abstract

Are the results of randomised trials reliable and are p values and confidence intervals the best way of quantifying efficacy? Low power is common in medical research, which reduces the probability of obtaining a 'significant result' and declaring the intervention had an effect. Metrics derived from Bayesian methods may provide an insight into trial data unavailable from p values and confidence intervals. We did a structured review of multicentre trials in anaesthesia that were published in the New England Journal of Medicine, The Lancet, Journal of the American Medical Association, British Journal of Anaesthesia and Anesthesiology between February 2011 and November 2021. We documented whether trials declared a non-zero effect by an intervention on the primary outcome. We documented the expected and observed effect sizes. We calculated a Bayes factor from the published trial data indicating the probability of the data under the null hypothesis of zero effect relative to the alternative hypothesis of a non-zero effect. We used the Bayes factor to calculate the post-test probability of zero effect for the intervention (having assumed 50% belief in zero effect before the trial). We contacted all authors to estimate the costs of running the trials. The median (IQR [range]) hypothesised and observed absolute effect sizes were 7% (3-13% [0-25%]) vs. 2% (1-7% [0-24%]), respectively. Non-zero effects were declared for 12/56 outcomes (21%). The Bayes factor favouring a zero effect relative to a non-zero effect for these 12 trials was 0.000001-1.9, with post-test zero effect probabilities for the intervention of 0.0001-65%. The other 44 trials did not declare non-zero effects, with Bayes factors favouring zero effect of 1-688, and post-test probabilities of zero effect of 53-99%. The median (IQR [range]) study costs reported by 20 corresponding authors in US$ were $1,425,669 ($514,766-$2,526,807 [$120,758-$24,763,921]). We think that inadequate power and mortality as an outcome are why few trials declared non-zero effects. Bayes factors and post-test probabilities provide a useful insight into trial results, particularly when p values approximate the significance threshold.