An underrecognized challenge in evaluating postmarketing drug safety.

The withdrawal of the cyclooxygenase (COX)-2–specific inhibitor rofecoxib (Vioxx; Merck) has generated a high-profile debate in the medical and lay press over when a signal suggesting the potential for harm from this drug was first apparent and what steps the medical community, the US Food and Drug Administration, and the pharmaceutical sponsor took and should have taken to address this issue.1,2 This debate, however, has glossed over a fundamental problem that the withdrawal of the drug serves to highlight—not how best to deal with a potential signal once it is described, but rather how to identify such important and initially unanticipated effects after a drug is marketed.