Comparing reporting rates of adverse events between drugs with adjustment for year of marketing and secular trends in total reporting.

The Food and Drug Administration has collected spontaneous reports on adverse events (AE) from manufacturers and individuals. These data provide useful information on the safety of marketed drugs. Due to many unique characteristics of this reporting system, the information is difficult to evaluate. Incidence rates for specific adverse events and drug combinations cannot be estimated. However, reporting rates (number of reports per market share) based on prescriptions can be computed. These reporting rates provide signals of serious adverse experience that may deserve attention. When the ratio of reporting rates is used for the comparison of two drugs of the same drug class, adjustments are needed for the marketing year and secular trends of all-drug-all-AE reporting. The Mantel-Haenszel procedure is used to combine the multiyear data into one summary statistic. Application of this analysis is illustrated on reports of upper gastrointestinal bleeding, perforation, and ulcer associated with nonsteroidal anti-inflammatory drugs, as given in Rossi et al. (12).