Being sceptical about meta-analyses: a Bayesian perspective on magnesium trials in myocardial infarction

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Abstract
Background There has been extensive discussion of the apparent conflict between meta-analyses and a mega-trial investigating the benefits of intravenous magnesium following myocardial infarction, in which the early trial results have been said to be ‘too good to be true’. Methods We apply Bayesian methods of meta-analysis to the trials available before and after the publication of the ISIS-4 results. We show how scepticism can be formally incorporated into an analysis as a Bayesian prior distribution, and how Bayesian meta-analysis models allow appropriate exploration of hypotheses that the treatment effect depends on the size of the trial or the risk in the control group. Results Adoption of a sceptical prior would have led early enthusiasm for magnesium to be suitably tempered, but only if combined with a random effects meta-analysis, rather than the fixed effect analysis that was actually conducted. Conclusions We argue that neither a fixed effect nor a random effects analysis is appropriate when the mega-trial is included. The Bayesian framework provides many possibilities for flexible exploration of clinical hypotheses, but there can be considerable sensitivity to apparently innocuous assumptions.