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pharmacoepidemiology and drug safety 2001; 10: 407±410 DOI: 10.1002/pds.615 ORIGINAL REPORT The role of databases in drug postmarketing surveillance y Evelyn M. Rodriguez MD, MPH*, Judy A. Staffa PhD, RPh and David J. Graham MD, MPH Of®ce of Postmarketing Drug Risk Assessment, Center for Drug Evaluation and Research, Food and Drug Administration, USA SUMMARY This paper describes the role of databases used for postmarketing surveillance of drugs at the United States Food and Drug Administration FDA). First we describe the Adverse Event Reporting System AERS), the largest database of adverse event reports in the world. Next, we explain the methods we have used for assembling these adverse event reports into a case series and analysing them, as well as techniques for employing drug use databases to construct reporting rates in the evaluation of drug safety issues. Finally, we discuss the FDA's use of the databases it accesses through its Cooperative Agreement Program to conduct high priority studies to support regulatory decision-making. Published in 2001 by John Wiley & Sons, Ltd. key words Ð pharmacoepidemiology; adverse drug reactions; clinical trials, phase IV; consumer product safety; pharmacovigilance INTRODUCTION The Adverse Event Reporting System AERS) is a relational database that was implemented in Novem- ber 1997 to replace the Spontaneous Reporting Sys- tem SRS), the ®rst database of adverse events reports of the United States Food and Drug Adminis- tration FDA). The SRS, which was started in 1969, is a database collection of all paper images of adverse events reports received by the FDA. In contrast, AERS is a longitudinal database where users can relate one report to subsequent follow-up reports to compile a single case. In addition, AERS technology allows users to encode and search reports using MedDRA Medical Dictionary for Regulatory Activities Termi- nology) and to export data into spreadsheets and other computer software for more complex analyses. AERS is an important resource to the FDA and to industry, and has been designed to accept electronic adverse event reports in compliance with the International Conference of Harmonization. The increased number of drugs on the market and an ever-increasing number of adverse event reports to the FDA have also increased the importance of the ef®ciencies in data searching and handling offered by AERS. In 1985, FDA received about 50 000 reports per year, versus more than 250 000 reports in 1999. The robustness of AERS enables the frontline safety evaluation staff to analyse these reports more easily and facilitates their manipulation in other formats. Seven general principles are considered in evalu- ating spontaneous reports of adverse events received by FDA. 1) There must be an appropriate temporal relationship such that drug exposure precedes the adverse event. 2) We consider the relationship between the underlying disease, the drug exposure, and the reported adverse event. For example, the exhaustive case analysis for cisapride identi®ed a problem with other drugs that inhibited the cyto- chrome P450 3A4 enzymes, the same enzymes that metabolize cisapride, or drugs that depleted serum electrolytes. Similarly, thorough case analysis for tro- va¯oxacin revealed that the risk of liver failure Received 29 March 2001 Published in 2001 by John Wiley & Sons, Ltd. Accepted 19 April 2001 This article is a U.S. Government work and is in the public domain in the USA. * Correspondence to: Evelyn M. Rodriguez MD, MPH, Division of Drug Risk Evaluation II, Of®ce of Postmarketing Drug Risk Assessment, Center for Drug Evaluation and Research, FDA, 5600 Fishers Lane, HFD-440, Rockville, MD 20857, USA. Tel: 301-827- 3172. Fax: 301-480-0628. E-mail: [email protected].

The role of databases in drug postmarketing surveillance

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