THE INSTITUTE OF MEDICINE (IOM) issued a report last September urging the Food and Drug Administration (FDA) to change the
way it operates, in order to achieve better balance in the agency's assessment of the risks and benefits of drugs. FDA commissioner
Andrew von Eschenbach responded a few weeks ago with a detailed safety program. FDA plans to develop safety report cards on
important new drugs, create an online drug-safety newsletter, and improve the agency's ability to detect safety signals by
accessing more health system databases. The leaders of the Center for Drug Evaluation and Research (CDER) also promise to
address the tension between pre- and post-approval staffs by orchestrating a "true culture change" that gives safety analysts
more authority over regulatory decisions.
The unstated goal of the program is to soften legislation that would require more significant organizational changes and impose
new mandates on manufacturers and regulators alike. Senators Charles Grassley (R-IA) and Chris Dodd (D-CT) continue to back
a bill establishing a separate drug-safety office at FDA. And Senators Edward Kennedy (D-MA) and Mike Enzi (R-WY) have offered
a bill requiring risk-mitigation strategies for all new drugs and mandatory clinical-trial registration.
The FDA announcement covered activities the agency can implement on its own, as long as it gains sufficient funding. The plan
does not address IOM proposals requiring congressional action, such as giving the agency authority to levy fines on companies
that fail to complete promised post-approval studies. The agency also did not respond to recommendations for special warning
symbols on high-risk products and limits on DTC advertising of newly approved drugs, an issue that is gaining attention in
Washington. But it seems clear that if FDA and industry want Congress to reauthorize the Prescription Drug User Fee Act (PDUFA)
by fall, they probably will have to accept some new legislative requirements designed to ensure the safety of medicines.
Fees for Safety
The FDA plan addresses IOM's recommendations on assessment and communication of risk information. But some of its proposals
fall short of what critics had demanded. For example, IOM had suggested a scheduled reevaluation of new drugs a year or so
after launch, as would occur under a conditional-approval system. The pilot plan to issue report cards on newly approved drugs
responds to that demand—but not completely. FDA proposes to evaluate adverse-event reports, additional clinical studies, and
epidemiologic information, starting with two or three new molecular entities (NMEs). These just now are being selected for
the pilot, so the first assessments won't appear for at least 18 months. But the reports will be made public, and the program
could be extended to all new drugs if it seems to provide a more complete picture of safety issues throughout the product
There also has been a clamor for FDA to publicly disclose more drug safety information from post-approval studies and adverse-event
reports. The industry, arguing that sponsors and regulators should have the opportunity to evaluate safety information before
publicizing it, has opposed the proposal. FDA has offered a compromise: It dropped its earlier proposal for a "Drug Watch"
Web site and proposes to launch an online newsletter with summaries of FDA post-marketing drug reviews, emerging safety issues,
and information on newly approved products. The summaries will be cleansed of confidential commercial information.
The Kennedy-Enzi bill would require all new-drug applications (NDAs) to include risk management plans (RiskMAPS), and the
IOM report urged further evaluation of such approaches. FDA says it will review one or two RiskMAPS every year and post the
results to help assess how effectively these programs address serious safety issues.