A panel of former FDA commissioners convened recently to exchange ideas on improvements to the agency, tackling issues ranging from restructuring FDA funding to enhancing the agency's legal authority to ensure drug safety.
In the end, the panelists agreed that the agency is sorely in need of appropriated funds to do its job properly and that future FDA commissioners need terms of sufficient length to effect changes.
The meeting, "A Conversation with FDA Commissioners: Strengthening the FDA," took place February 21, 2007, at The George Washington University, Washington, DC, and was sponsored by the university's School of Public Health and Health Services and the Project on Scientific Knowledge and Public Policy.
LEADERSHIP, POLITICS, AND A LOSS OF CREDIBILITY
The lack of consistent leadership at FDA over the past several years has led to a loss of the agency's credibility, the panel agreed. FDA leadership has suffered recently as the agency has had to rely on interim or acting commissioners, Dr Henney said.
"You can't have a commissioner every 18 months," Dr Kessler said. "You can't run an agency with a commissioner who's there for such a short period of time."
The panelists said increased politicization of FDA has also led to a credibility gap. Dr Kennedy noted the harm done by political appointees to FDA, who have too often reinterpreted scientific findings in the pursuit of political policies. He referred to science and policy as the "horse and cart" of FDA decisions. "The science horse ought to go first. The public is disillusioned when the policy cart is coming first," he said.
Dr Kessler said: "If you're going to do something for political reasons... at least say that you're going to do it for political reasons. Admit it, don't do it under cover; you lose credibility. And the agency has lost a lot of credibility."
A CALL FOR RESOURCES
"Adequate resources are a long-standing problem and one we're continuing to ignore at our own peril," Dr Wood said.
In January 2007, FDA proposed an increase in annual user fee collections of $87.4 million, bringing fees to a total of $392.8 million, to broaden and upgrade the agency's drug safety program. The Prescription Drug User Fee Act (PDUFA) authorized the user fee program in 1992.
According to Dr Kessler, user fees came at a moment of desperation during the Reagan administration and were the result of a down cycle of appropriation. The current balance of FDA funding for the drug review process, with two-thirds coming from user fees, is a cause for concern.
The former commissioners said that PDUFA has created unease with the public, who perceive the program as the pharmaceutical industry's attempt to influence the review process. The answer lies in increased appropriations to FDA from Congress, Dr Henney said. "If they [Congress] really wanted to look long and hard, FDA would no longer be under the purview of the agricultural appropriations committees... by the time the allocations come out, and the interests of the agricultural areas are satisfied, there [are] very limited resources the agency can ever hope to receive out of that process," she said.
PDUFA is "not the right way for Congress to exercise its responsibility to all people," Dr Kennedy said. "Not relying on user fees is important in the long run."
INCREASING FDA AUTHORITY TO ENSURE DRUG SAFETY
Additional legal authority to address postmarket surveillance and drug safety is long overdue at FDA, Dr Young said. At present, FDA must negotiate, rather than order, label changes for drugs that are demonstrated to be less safe than initially believed, and the agency has no recall authority when it spots safety problems with drugs already on the market.
"I would urge very strongly an increased ability of the agency to monitor safety once a drug is on the market, whether through mandatory phase 4 or better focus on postmarket adverse reactions," Dr Young said. This authority is key, given that drug approvals are based on data from a few thousand patients and yet, once approved, these drugs may be marketed to millions of potential patients.
Dr Kennedy added: "We desperately need a really effective national system for the epidemiology of adverse drug reactions." In the case of rofecoxib, data on adverse drug reactions had to be obtained from Kaiser Permanente rather than through the manufacturer, he said.
Management plans for drugs "make a lot of sense and should be executed," Dr Kessler said. "A strong, important step in the right direction is the Enzi-Kennedy bill. Having a management plan at the time of approval with an array of options will only enhance the drug approval and safety record."
The bill to which he referred, dubbed Risk Evaluation and Management Strategy (REMS), was introduced by Senators Edward Kennedy (D–Mass) and Michael Enzi (R–Wyo) and would provide FDA with enhanced authority to monitor the safety of newly approved drugs and encourage additional research on these agents.
REMS would require annual reviews of newly approved drugs for 3 years and a plan to assess known serious risks and to identify unexpected serious risks. Manufacturers would be required to file adverse drug reports 15 days after the start of marketing, quarterly, and then annually.
Other requirements would include postmarket clinical trials, restrictions on direct-to-consumer advertising for new medications, and a Drug Safety Oversight Board to mediate disputes between pharmaceutical manufacturers and FDA over REMS.
A NEW ERA OF PHARMACEUTICAL DEVELOPMENT?
Dr Kessler raised the possibility of FDA serving an unspecified role in facilitating a new model of drug development. He called the current model in which drugs are developed for the masses, so-called "blockbuster" drugs, not sustainable.
"The notion that there are drugs that millions and millions of people will be able to take safely... that's what has gotten us in trouble," Dr Kessler said. "[With this approach] of course there are going to be serious adverse reactions."
A new paradigm in medication and drug development will be one in which the right drug at the right dose will be selected for the right person with the right disease, he said. "There's a whole economic discussion that needs to be had because big pharma can't be supported by that model, and won't be supported."
Dr Kessler acknowledged that all drugs can cause side effects and adverse reactions, but he said the risks are more acceptable when the drugs are tailored to the people who are most likely to benefit rather than marketed to the masses.
Dr Kessler predicted that in the next decade, many more pharmaceutical companies will be willing to develop products with a market potential of $200 million to $300 million, rather than the billion-dollar market they currently target.
RESTORE RESEARCH CAPABILITIES
Budget stripping has led to an FDA without research capabilities related to regulation, Dr Henney said. The agency receives no funding for its members to attend scientific meetings or to receive continuing medical education.
"You want people at the top of their game, looking at the scientific evidence, coming into the agency in terms of one of those product reviews," she said. "You don't want someone whose knowledge is even 5 or 10 years old."
There is a need for pharmacogenomic studies to determine which patients may respond optimally to particular drugs, Dr Kessler said, but he questioned whether such studies are the responsibility of industry or academia. These types of studies would require a level of science "that the agency has not seen in recent years," he said.
CONFLICTS OF INTEREST AND ADVISORY COMMITTEES
Relationships between academia and industry have flourished and the objectivity of FDA advisory committees has come under greater scrutiny since the passage of the Bayh-Dole Act of 1980, which allows universities and businesses operating with federal contracts to assume exclusive control of government-funded inventions. "The question becomes one of disclosure and how much of a conflict can you have and still be seen as an objective and knowledgeable reviewer," Dr Henney said.
One of the inherent problems with advisory panels is that participation in the panels requires experience with clinical trials, most of which have been conducted under sponsorship outside of the National Institutes of Health (NIH), Dr Young said. "We're not going to bring basic scientists in to judge clinical trials," he said. "You need to have people with clinical experience in the topic. That's the challenge. But the appointees to advisory committees should be under FDA, not under political, scrutiny."