Compromised? The FDA's user fee model has once again come under scrutiny.

Among the many casualties that lie in the wake of the worldwide withdrawal of rofecoxib (Vioxx; Merck), the FDA can in many ways be said to have taken the greatest hit. Many sections of the lay and academic press have once again accused the FDA of being in the pocket of the pharmaceutical industry by relying on industry's money to fund the drug approval process.

There is no doubt that the implementation of the Prescription Drugs User Fee Act (PDUFA) has intensified relationships between the agency and industry, but whether it has altered the FDA's objectivity is open to question.

The approval rate of new drugs has increased slightly from 76% for pre-PDUFA drugs to 81% since PDUFA. Drug safety, when measured in crude terms by drug withdrawals, has not increased noticeably, although this does not take into account the safety or risks of drugs still on the market.

What has dramatically changed is the increasing number of products approved in a single review cycle. More staff at the FDA, and greater dialogue between the agency and companies during the clinical development process, has helped, but so has introducing 6- or 12-month approval deadlines and performance goals.

These time limits mean that reviewers must in essence reject a New Drug Application if they want to see additional studies before approving the drug, says Mary Olson, Associate Professor of Health Policy and Administration at the Yale School of Public Health. “Reviewers may not be willing to reject a drug application that has evidence of efficacy even though they face some uncertainty about drug safety and would like to see an additional study of a safety-related question,” says Olson. “This explains why agency requests for post-marketing safety studies have increased in the PDUFA era.”

The main flaw with PDUFA is that it by and large allows funding to be used solely on reducing review time, says Raymond Woosley, President of The Critical Path Institute at the University of Arizona. “Restricting funds to mostly reviewing new drugs in effect compromises the FDA,” says Woosley. “It's not anyone's intent to let user fees drive the agency, but the sheer weight of it does.”

“What is desperately needed is increased funding from federal and/or filtered user-fee sources for post-marketing safety,” says Eve Slater, who has worked at the US Department of Health and Human Services as well as Merck. The fee would go towards improving the IT systems and the personnel to process the data. “For the IT system, we're talking about an upgrade of around US$50 million and a head count of around 30 additional people,” says Slater. “So we're not talking about a huge amount, relatively speaking.”

Devoting more FDA funds to post-approval clinical trials and/or an expanded role of epidemiology studies would help restore some public confidence in the user fee system, says Daniel Carpenter, Professor of Government at Harvard University. “The fully capitalized benefits of regulatory approval are far in excess of the actual dollar value of a user fee — and that would be true even if the user fee was tripled or quadrupled.”

“Will the public be reassured if they know safety studies are funded by user fees?” asks Kenneth Kaitin, Director of the Tufts Center for the Study of Drug Development. “In an ideal world Congress would commit the resources to fully fund the process, to eliminate the appearance of conflict of interest,” says Kaitin. “But we don't live in an ideal world, and until I see evidence that the FDA is compromised by the current relationship with industry, I don't see an alternative or better system that is available at this point.”