Author Affiliations: Departments of Biostatistics
and Epidemiology, Medicine, and Pharmacology, Center for Clinical Epidemiology
and Biostatistics, Center for Education and Research on Therapeutics, University
of Pennsylvania School of Medicine, Philadelphia.
Published online November 22, 2004 (doi:10.1001/jama.292.21.2643).
Health care practitioners and patients seek safe and effective drugs.
However, no drug is completely safe; all drugs have toxic effects that must
be balanced with their benefits in deciding whether they should be marketed
or used in any given person. To inform such decisions, the United States relies
on a drug approval system whereby preclinical studies precede 3 phases of
clinical studies. Collectively, these usually include 500 to 3000 exposed
patients and 2 or more confirmatory trials, demonstrating before marketing
that a drug is effective and reasonably safe for its recommended use.1 Thus, adverse reactions occurring in 1% or more of
exposed patients are usually well described upon marketing. However, rarer
adverse reactions are not well characterized until after marketing.2 This reflects a deliberate societal decision to balance
delays in access to new drugs with delays in information about rare adverse
reactions. To provide the missing information, the United States maintains
a postmarketing surveillance system including passive collection of spontaneous
reports of adverse drug reactions (ADRs) to generate signals of possible adverse
drug events. This is supplemented by formal pharmacoepidemiology studies testing
those hypotheses, confirming or disproving potential signals from the spontaneous
reporting system (SRS).2
Strom BL. Potential for Conflict of Interest in the Evaluation of Suspected Adverse Drug ReactionsA Counterpoint. JAMA. 2004;292(21):2643-2646. doi:10.1001/jama.292.21.2643