Evaluation of Serious Adverse Drug Reactions

Abstract

The Food and Drug Administration (FDA) and pharmaceutical manufacturers conduct most postmarketing pharmaceutical safety investigations. These efforts are frequently based on data mining of databases. In 1998, investigators initiated the Research on Adverse Drug events And Reports (RADAR) project to investigate reports of serious adverse drug reactions (ADRs) and prospectively obtain information on these cases. We compare safety efforts for evaluating serious ADRs conducted by the FDA and pharmaceutical manufacturers vs the RADAR project. We evaluated the completeness of serious ADR descriptions in the FDA and RADAR databases and the comprehensiveness of notifications disseminated by pharmaceutical manufacturers and the RADAR investigators. A serious ADR was defined as an event that led to death or required intensive therapies to reverse. The RADAR investigators evaluated 16 serious ADRs. Compared with descriptions of these ADRs in FDA databases (2296 reports), reports in RADAR databases (472 reports) had a 2-fold higher rate of including information on history and physical examination (92% vs 45%; P<.001) and a 9-fold higher rate of including basic science findings (34% vs 4%; P = .08). Safety notifications were disseminated earlier by pharmaceutical suppliers (2 vs 4 years after approval, respectively), although notifications were less likely to include information on incidence (46% vs 93%; P = .02), outcomes (8% vs 100%; P<.001), treatment or prophylaxis (25% vs 93%; P<.001), or references (8% vs 80%; P<.001). Proactive safety efforts conducted by the RADAR investigators are more comprehensive than those conducted by the FDA and pharmaceutical manufacturers, but dissemination of related safety notifications is less timely.