Reformers want to give FDA more clout, but agency officials say internal changes will help fix drug safety problems.
Consumer advocates have launched a "Fix the FDA" campaign as drug safety incidents continue to prompt questions about how FDA reviews new drugs and monitors those on the market. The reformers want to give the agency more funding and post-approval regulatory clout, but FDA officials maintain that new internal initiatives can fix its problems.
At hearings in March before the Senate Health, Education, Labor and Pensions (HELP) Committee, panel chairman Mike Enzi (R-WY) and lead Democrat Edward Kennedy (D-MA) discussed developing bipartisan legislation to address a range of proposals. Kennedy complained that it took five years for the public to learn that Vioxx may double the risk of heart attack or stroke, while user fees allow FDA to review new drugs quickly. But Kennedy also agreed with Enzi that "overreacting could be as dangerous as doing nothing," and that it is critical to "find the right approach."
Senate Finance Committee chairman Charles Grassley (R-Iowa) has been leading the campaign to establish a separate office to oversee drug safety issues, similar to boards that review highway and airline accidents. Grassley and others originally demanded a drug safety operation independent of the agency, but FDA officials have been fairly successful in explaining that it makes sense to keep this operation at the agency, and preferably within the Center for Drug Evaluation and Research (CDER), where it now is.
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Pharma companies support FDA contentions that it's critical for the people who evaluate a drug application in the first place to play a role in monitoring the product over its full lifecycle. At the Senate hearing, FDA acting deputy director Janet Woodcock described drug regulation as a continuum between pre- and post-market monitoring that requires a careful balancing of risks and benefits, a perspective that might decline in an operation that focuses solely on safety problems.
Even if Congress decides to leave FDA drug safety oversight structurally intact, reformers are pressing for a number of additional changes that would give FDA more clout:
Strengthen FDA authority to require labeling changes on approved drugs While the agency usually reaches agreement quickly with sponsors on additional warnings and other labeling changes, the Vioxx case shows that such negotiations can take months. Sandra Kweder, deputy director of CDER's Office of New Drugs, acknowledged at the first Senate hearing that the ability to require changes in labeling would be "very helpful" to the agency.
Require sponsors to complete post-approval studies Kweder also supports policies allowing FDA to require a clinical trial to address specific safety issues that emerge after a drug is on the market. FDA now can mandate additional studies only for those drugs approved under its accelerated approval process. The agency can ask a sponsor to conduct certain Phase IV trials, but cannot do much if the marketer fails to keep its commitments— not an uncommon circumstance.
Boost FDA authority to remove problematic drugs from the market Most drug withdrawals are voluntary, although they often occur as a result of FDA urging. The agency has to show that a drug poses an imminent risk to pull it off the market, and that's usually difficult to do. Several proposals would give FDA authority to levy fines or impose other penalties on marketers that fail to comply quickly to post-approval safety concerns.
Expand information on clinical trials Congress wants to strengthen and expand clinical trial registries to better inform the public about investigative drugs under study; there also is a push for public disclosure of clinical trial results, including those that end up producing unfavorable results.
Pharmaceutical companies say they are posting more research data voluntarily, but observers contend that a specific mandate is needed to gain full access to important safety information.
Increase FDA resources Patient advocates feel that FDA's budget is too lop-sided, with most resources devoted to new drug approvals and too little to post-approval monitoring. The Administration's budget plan for 2006 proposes to expand funding for drug safety surveillance. However, that amount is still far below the levels needed to conduct all the proactive safety analyses and epidemiological studies that safety experts say are necessary.
FDA is lobbying for Congress to hold off on legislative change until the agency has a chance to see if new initiatives will address these problems. FDA is establishing a drug safety oversight board to provide an objective perspective on the safety of drugs. A new grievance process will provide a forum for dissenting FDA scientists to air their concerns. The latest drug safety information will be posted on FDA's new Drug Watch website to prevent delays between FDA learning about a safety problem and the information reaching the public, as occurred with Vioxx.
FDA also has finalized three draft guidances on managing the risks in medical products. And the Institute of Medicine is beginning work on a review of the drug approval process, which should examine all these issues over the next two years.
Critics contend that the safety board and website are just window-dressing and will lack the teeth needed to address serious safety problems. Meanwhile, more legislative proposals are likely to surface, and more inquiries will be launched. The main fear among FDA leaders is that poorly designed legislation might jeopardize risk-taking in the drug development process just as more innovative research methods and cutting-edge analytical approaches are emerging.
Jill Wechsler is Pharmaceutical Executive's Washington correspondent.