NEJM: User-Fee Law Makes FDA “Accountable” to Big Pharma

With the highly controversial Prescription Drug User Fee Act (PDUFA) set to expire this September, a debate is raging through Congress, the U.S. Food and Drug Administration (FDA), the health-care industry, and the pharmaceutical industry about the relative merits of the user-fee program. To some, having drug companies pay user fees to the FDA is a necessary way to make sure the agency has an adequate budget to work with. However, a growing number of critics believe that the system leaves federal regulators beholden to the industry it is supposed to monitor.

An editorial published in this week’s New England Journal of Medicine has explicitly called for the dismantling of the user-fee system. “User fees now account for more than 40 percent of the budget of the FDA division that reviews new drug applications,” writes Dr. Jerry Avorn, a professor at Harvard Medical School. “Colleagues at the FDA have told me of a worrisome side effect of PDUFA: the growing sense that the organization is accountable to the industry it regulates. One FDA scientist who was often criticized for being too concerned about drug-risk data was told by his supervisor to remember that the agency’s client was the pharmaceutical industry.”

Despite growing concerns about conflicts of interest at the FDA’s Center for Drug Evaluation and Research (CDER), if anything the FDA has been actively working to boost Big Pharma user fees, not eliminate them. In January, the FDA announced a proposal to dramatically increase user fees collected from the pharmaceutical industry by $87.4 million, bringing the grand total to nearly $400 million.

The Prescription Drug Use Fee Act (PDUFA) was first approved in November of 1992, allowing funds from the pharmaceutical industry to be added to the FDA’s appropriations in order to bolster the FDA’s drug-review program. “At that time,” notes Dr. Avorn, “the FDA was having difficulty evaluating new drugs quickly and efficiently. The agency had been shaken by sit-ins held by AIDS activists protesting long review times, which they argued were killing them. The staff of the FDA was too small to adequately assess all the new drug applications the agency received.

“But the era’s dominant ideology derided ‘bloated government’ and demanded that Congress rein in ‘runaway spending.’ In that climate, the sensible policy solution provide the FDA with more federal funding to hire enough people to carry out its mission was a nonstarter. But just as the FDA’s slowness may have been costing patients with AIDS their lives, it was costing pharmaceutical manufacturers their income. So the industry stepped in and helped to design a plan under which companies would pay the salaries of agency employees who reviewed the companies’ submissions.”

PDUFA must be reauthorized by Congress every five years, which happened mostly without issue in 1997 and 2002. This time around, however, reauthorization by Congress is far from a given as many legislators seek to overhaul the FDA. Lawmakers in the Senate opened debate earlier this week to determine whether or not to keep the PDUFA system going. While Congress sees the PDUFA renewal issue as a chance to give much-needed repairs the drug-approval process, the FDA and the pharmaceutical industry are, not surprisingly, highly resistant to any changes to the system.

At very least, some lawmakers see PDUFA reauthorization as an opportunity to add some critical safety measures to the system. One bill, co-sponsored by Democratic Sen. Ted Kennedy and Republican Sen. Mike Enzi, includes several additional provisions, including placing limits on direct-to-consumer advertising for newly approved drugs, increasing public disclosure of clinical-trial results, and improving the FDA’s post-market monitoring of drugs they have previously approved.

Several other amendments are being bandied about that would also be tied to the PDUFA extension. These additional proposals may include strengthening the independence of FDA scientists and eliminating conflicts of interest among the FDA’s panel experts. (To be fair, the FDA has recently made significant strides to combat the latter problem.)

According to Dr. Avorn’s NEJM commentary, “There were problems with the user-fee approach from the beginning. The original legislation required that no portion of companies’ fees (about half a million dollars per drug reviewed) could be spent to evaluate drug side effects after approval–the time when many important safety concerns become apparent. The new law mandated strict deadlines for approval decisions. To comply, the FDA reassigned staff scientists to work on new drug applications, pulling the scientists from other regulatory activities.”

To most observers, many of these initial problems still persist. “Other agency staffers report pressure to rush through the drug-approval process,” notes Dr. Avorn, “although the FDA’s regulatory review times are already among the shortest in the world. Evidence is accumulating that this emphasis on speed may lead to problematic decision making. Data analyzed by Daniel Carpenter, a professor of government at Harvard University, suggest that drugs approved just before PDUFA deadlines are far more likely than those approved at other points in the review cycle to cause safety problems after they are in widespread use.”

To be sure, the severe health risks that led to the removal of Vioxx (rofecoxib) from the market in 2004 caught the attention of Congress and spurred lawmakers to take a much closer look at the FDA’s drug-approval process. While proponents of PDUFA claim that the additional user fees would make the safety-review system more robust, Dr. Avorn makes the valid point that “appropriately conducted studies would have revealed the cardiovascular toxicity of rofecoxib well before the end of its five-year run. By that point, the country was spending $2.5 billion per year on the drug, about a billion of which was public money. Documenting the drug’s risks and getting it off the market just one year sooner would have paid for a robust system of drug-safety surveillance for four years, without relying on a dime of user fees or additional taxpayer dollars. We spend more than $2 billion on the Iraq war in about a week. A nation as wealthy as ours can afford what it chooses to afford.”

In fact, as explained, the PDUFA system lacks virtually any provisions that would strengthen post-market surveillance of potentially dangerous drugs, a key failure that many hope Congress will address should they decide to re-approve the law. As it stands now, the user fees that roll into the FDA from the drug companies are used in pursuit of one overriding goal: getting Big Pharma’s products on the market as quickly and painlessly as possible.

Dr. Avorn notes: “Most federal regulatory agencies do not derive such a large proportion of their operating budgets from the industries they oversee. Nor is it typical for such relationships to be negotiated so cozily between the government and the trade group representing the industry. Yet the current FDA proposal for PDUFA renewal was developed in concert with the Pharmaceutical and Research Manufacturers of America. No similar influence has been exerted by any other group.”

Dr. Avorn and like-minded FDA critics sincerely hope that Congress does not squander this opportunity to make a difference. “Many in Congress still believe that the user-fee system is saving the public money,” says Dr. Avorn. “That view is as invalid as the smug conclusion of the hospital administrator I spoke with years ago.” That administrator had told Avorn that the hospital’s “grand-rounds program,” in which doctors received speaking fees, free food, and other gifts from the drug industry, helped improve meeting attendance and helped protect the hospital’s tight budgets. Of course, it also provided a major boost to the products that the drug companies were promoting in the first place.

“In regulatory policy, as in grand rounds,” says Dr. Avorn, “there’s no such thing as a free lunch.”

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