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Meta-analyses and megatrials: neither is the infallible, universal standard
  1. Toshi Furukawa
  1. Professor of Psychiatry, Evidence-Based Psychiatry Center
    (, Nagoya City University, JAPAN;

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Nowadays, most would agree that we need evidence from randomised control trials (RCTs) to evaluate the effectiveness of a health intervention. It used to be that we did not have enough RCTs in mental health; the irony today is that at times it seems we have too many of them, especially when they draw conflicting conclusions.

A natural solution is to seek “stronger” evidence. Meta-analysis might provide that evidence but, alas, meta-analyses sometimes do not agree among themselves either.1 Another possible solution is a bigger and better trial, a megatrial (also known as the large, simple trial). Unfortunately megatrials and meta-analyses do not always agree either: one group has claimed that—taking megatrials as the gold standard—meta-analyses drew wrong conclusions 35% of the time2; another group estimated the degree of disagreement to be between 10% and 23%.3 Megatrials sometimes do not agree with each other either, and discrepancies among megatrials are just as large as those between meta-analyses and megatrials.4

These discrepancies reinforce a conclusion that the days of dogmatic advocacy of the methodological hierarchy of evidence are over. …

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