Drug Safety Oversight: Before and After FDA Approval

Congress and the Bush Administration are wrangling over how to strengthen the drug safety oversight activities at the FDA in the wake of the recent controversies over cyclooxygenase-2 inhibitors and pediatric antidepressants. The White House intends to create an independent Drug Safety Oversight Board (DSB) within the FDA. Several key senators like the idea but insist that the DSB be separate from the FDA to keep it from being "under the thumb" of that agency.Several senators commented (at press time) that a structural conflict of interest exists in the FDA because the Center for Drug Evaluation and Research (CDER), which approves new drugs, also houses the Office of Drug Safety (ODS), which can recommend that drug approvals be reevaluated. Some senators were crafting legislation to restructure the FDA and make the ODS independent of the CDER.The pharmaceutical industry has been urging caution: "Let's not be stampeded into hasty, premature action," said Jeff Trewhitt, spokesman for the Pharmaceutical Research and Manufacturers of America, the branded-drug industry trade group. "We have time to wait and see what the Institute of Medicine recommends," he told Applied Neurology. The study by the Institute of Medicine-to assess the FDA's drug safety oversight mechanisms and recommend possible courses of action-is expected later this year.Whether the FDA's drug safety office and oversight board exist within the agency or are bureaucratically separate will probably make little difference, according to Thomas R. Swift, MD, president-elect of the American Academy of Neurology and professor emeritus at the Medical College of Georgia. "Why are we starting a new bureaucracy now? I have my doubts whether any [structural change] would make a difference," he told Applied Neurology. Revelations of unanticipated and sometimes harmful post-market side effects are inherent in the drug approval system, Swift said. Clinical trials would take far too long to conduct if all side effects had to be uncovered before a drug is approved."People think it's some kind of failure of the process, but it's not a failure so much as it is the way the process is built," Swift explained. "The patients need the drugs and the pharmaceutical companies can't be hanging there for too long or they wouldn't be putting the time into developing the drugs. It's always a tradeoff, and it's never going to be a perfect system."Neurologists came up against this several years ago after Wallace Pharmaceuticals (now MedPointe Pharmaceuticals) began marketing the highly effective anticonvulsant felbamate (Felbatol). It wasn't until the drug had been in use for some time that reports of fatal aplastic anemia and hepatic failure began to emerge. Felbatol wasn't withdrawn, but neurologists now are advised to prescribe the medication after receiving informed patient consent and only when the benefits outweigh the risks.1Under the Bush Administration's plan, an 18-member DSB would consist of FDA and other federal government officials, consult with outside experts, resolve disagreements within the CDER over drug safety issues, oversee updates to a Drug Watch Web site intended to publicize possible serious side effects identified in clinical studies, and assess the need for patient information guides. The agency's planned Drug Watch Web site will post emerging information about possible serious side effects or other safety risks from approved drugs when the information has the potential to alter the risk/benefit analysis and affect patient selection or monitoring decisions."We're not exactly sure we like that provision," said one drug industry insider, speaking on condition of anonymity. "If one new study shows a negative result and is published, yet 2 or 3 previous studies showed positive results, they should all be published alongside each other so doctors and patients can see the results in context."Ted Agres, MBA, is a freelance writer in Washington, DC.REFERENCE1. French J, Smith M, Faught E, Brown L. Practice advisory: the use of felbamate in the treatment of patients with intractable epilepsy: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 1999;52:1540-1545.