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The relation between treatment benefit and underlying risk in meta-analysis

^a Medical Statistics Unit, London School of Hygiene and Tropical Medicine, London WC1E 7HT, ^b Department of Medical Statistics and Evaluation, Royal Postgraduate Medical School, London W12 0NN, ^c Imperial Cancer Research Fund Medical Statistics Group, Centre for Statistics in Medicine, Institute of Health Sciences, PO Box 777, Oxford OX3 7LF

Correspondence to: Mr Sharp.

In meta-analyses of clinical trials comparing a treated group with a control group it has been common to ask whether the treatment benefit varies according to the underlying risk of the patients in the different trials, with the hope of defining which patients would benefit most and which least from medical interventions. The usual analysis used to investigate this issue, however, which uses the observed proportions of events in the control groups of the trials as a measure of the underlying risk, is flawed and produces seriously misleading results. This arises through a bias due to regression to the mean and will be particularly acute in meta-analyses which include some small trials or in which the variability in the true underlying risks across trials is small. Approaches which previously have . . . [Full text of this article]

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