Congress Responds to the IOM Drug Safety Report—In Full

Abstract

THE US DRUG SAFETY SYSTEM DEVELOPED FITFULLY throughaseriesofhistoricalaccretions, typically inthe wakeofmajordrugsafetyscandals.In1962,largelyprecipitatedbythethalidomidetragedy,theKefauver-Harris amendments to the Federal Food, Drug, and Cosmetic Act required the sponsor to provide “substantial evidence” of both safety and efficacy during a premarket evaluation. The resulting multistage approval process improved the evidence base for premarket regulatory decision making about drugs, but it also created, as an unintended consequence, a postapproval environment inwhichsponsorswere largely free fromrequirements for additional evaluations. At approval, the sponsor’s scientific teamsresponsible formeetingUSFoodandDrugAdministration (FDA) requirements were generally replaced by marketing teams,andthemanufacturer’s efforts, energies, and studies were generally directed toward marketing its drugs. The formulaic preapproval evaluation process, even though usually of high quality, slowed drug approval. The 1992 Prescription Drug User Fee Act (PDUFA) provided new funds fromuser fees, limited their use to speeding preapproval evaluations, set timelines for reviews, and thus brought drugs to market more quickly. As the United States became increasingly the country of first launch for many new drugs (from 2% in 1980 to 60% in 1998), the US postmarketing safety systemaccordinglysharedalargerresponsibility for theearlydetection of safety signals. For the first 10 years following enactment of PDUFA, however, Congress prohibited the FDA from applying user fees to drug safety and provided no additional funds for monitoring marketed drugs. Not until the PDUFA reauthorization of 2002 was the FDA permitted to apply some user fees for selected safety issues. In effect, Congress largely entrusted the detection, evaluation, and timely reporting of postmarketing safety issues to the pharmaceutical industry. The withdrawal of rofecoxib and other drug safety problems have again focused attention on the limitations of the US postmarketing system. In response to an FDA request, the Institute of Medicine (IOM) undertook a thorough assessment and issued a comprehensive set of recommendations for reform. The major theme of the report was the need for an ongoing effort to acquire, integrate, and communicate information about a drug’s risks and benefits during its entire market life. This “lifecycle” approach requires the translation of premarket safety signals into high-quality postmarketing studies, sophisticated active surveillance to identify new serious safety signals, and timely assessments of the drug’s riskbenefit profile. While the FDA has already responded in part to some recommendations, others dealing with the agency’s resources and authorities required congressional action.