The critical role of risk-benefit assessments in cancer prevention.

Controversy is building around agent development for cancer prevention. The withdrawal of rofecoxib (Vioxx, Merck) from the market and safety concerns raised by studies of other cyclooxygenase-2-selective inhibitors and an over-the-counter nonsteroidal anti-inflammatory drug have alarmed patients, physicians, and regulatory authorities. Evidence of nonsteroidal anti-inflammatory drug–associated cardiovascular toxicity—of relatively low frequency but significant magnitude—reminds us of the critical role that risk-benefit assessments play in agent development for cancer prevention. The placebo-controlled design of cancer prevention trials explains in part why these toxicities came to light only recently. Although this could dampen industry’s willingness to commit resources to cancer prevention, it also has the potential to stimulate creativity in clinical research and transform regulatory oversight in productive and meaningful ways. Our response to this challenge will dictate the pace of progress in cancer prevention research.