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To the Editor.—In their review and discussion of relevant issues in comparisons between meta-analyses and large randomized controlled trials,¹ Ioannidis and colleagues propose to explain why our external comparisons² (comparing large randomized controlled trials with previous meta-analyses) might produce larger differences than the internal comparisons used by Villar et al³ and Capelleri et al⁴ (they recalculated the results of each meta-analysis after removing the largest trial and then compared these results with those of the large trial that had been removed). However, we do not think the Villar-Capelleri protocol is a valid method of testing the extent of concordance between meta-analyses and large randomized controlled trials because it has an important flaw. It does not test the meta-analysis as it was published (the issue of interest) but a new version, with a different result, which excluded the large trial and only included small trials in the analysis. The meaning . . . [Full Text of this Article]

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