Meta-analysis of rare and adverse event data.

Potentially beneficial drugs may have side effects. Such adverse events may be serious but rare, making their effect difficult to quantify, or even their identification problematic within randomized controlled trials. Meta-analysis provides a means of combining such outcome data across a series of studies and provides a more powerful analysis than is possible from a single study. However, meta-analysis of adverse event data presents some unique methodological challenges. Procedural issues pertaining to study selection and the inclusion of both randomized and observational data are discussed. The statistical problem of combining rare outcomes is also considered at length. Model choice, continuity corrections, exact statistics, Bayesian methods and sensitivity analysis are all covered. The application of results from adverse event meta-analyses to clinical and economic decision models is also considered. A number of examples are presented to illustrate the key points.