Current US drug safety system is moving toward a delay in drug approval

May 3 2006

In the May 3 issue of the Journal of the American Medical Association, Brian L. Strom, MD, MPH, Professor of Public Health and Preventive Medicine and Chair of the Department of Biostatistics and Epidemiology at the University of Pennsylvania School of Medicine, analyzes the limitations of the current system of drug-safety monitoring and proposes a solution that addresses overly aggressive early marketing practices; an absence of incentives to complete post-marketing safety studies; direct-to-consumer (DTC) advertising that can promote non-critical use of "blockbuster" drugs; the current trend toward delaying drug approval; and public misunderstanding about the safety of drugs.

As Strom writes, "the net effect of [the current system] is that the public misunderstands drug safety, believing that a drug is safe at the time of marketing, while [adverse] events occurring as frequently as 1 in 1000 are predictably undetected."

Strom proposes an alternative approach with three elements: conditional approval, an empowered US Food and Drug Administration (FDA), and a complementary nongovernmental organization.

When a drug is initially approved, it should ideally enter a period of conditional approval, he says. In this period, marketing, especially DTC, would be restricted. Drug labels would need to be clearly marked that the drug's approval is conditional and has only been studied in a limited number of patients. Removal of label caveats would depend on the outcome of subsequent studies and their findings, depending on the numbers of individuals in the studies, and the risk and novelty of the drug, as well as addressing all premarketing safety questions.

"The current system is moving toward a delay in drug approval, still followed by optional postmarketing studies," notes Strom. "Instead, the proposed approach would be conditional approval followed by postmarketing studies required before the condition is removed."

Secondly, Strom maintains that the FDA needs an increased ability to regulate drugs after marketing, so that it can require post-marketing studies and labeling changes as a rule, rather than those changes being subject to negotiation between the regulatory agency and industry. It also needs substantially more resources for the postmarketing study of drug safety.

Strom concludes by proposing that an independent, nongovernmental organization is needed for nonregulatory tasks that are not within the mission of the FDA. Since many of these tasks are academic in nature - for example, performing postmortem examinations in the event of drug disasters or developing new pharmacoepidemiological methods - he suggests that the Agency for Healthcare Research and Quality (AHRQ)-funded Centers for Education and Research in Therapeutics (CERTS) or the Institute of Medicine (IOM) might play a role.

"A key benefit of this proposed approach for the public would be that drug use immediately after marketing would be reduced to those who truly need the drug, in whom the risk-benefit balance in the face of uncertainty is more favorable," Strom says.