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This penetration of commerce into the province of science isn't limited to continuing medical education. Since 1992, the United States has relied heavily on the pharmaceutical industry to pay the salaries of Food and Drug Administration (FDA) scientists who review new drug applications. The Prescription Drug User Fee Act (PDUFA) is now up for its periodic 5-year renewal, and Congress seems ready to reauthorize it with the same short-sightedness that afflicted that naive hospital administrator.
PDUFA was enacted at the end of the presidency of George H.W. Bush, when many in Washington believed that government was at the root of most of the country's problems. At that time, 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.
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. Several were taken from the Office of Drug Safety, which conducts adverse-effects surveillance — a move that helped to shrink and demoralize that unit.
User fees now account for more than 40% of the budget of the FDA division that reviews new drug applications (see bar graph). 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. "That's odd," he replied. "I thought our clients were the people of the United States." Other agency staffers report pressure to rush through the drug-approval process, 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.1
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In 2004, the public was shocked to learn that rofecoxib (Vioxx, Merck) could remain in widespread use for 5 years even though the drug nearly doubled the risk of myocardial infarction and stroke. Its withdrawal from the market aroused serious doubts about the adequacy of the FDA's drug-safety surveillance system. Last year, the Institute of Medicine (IOM) and the Government Accountability Office (GAO) released influential reports concluding that the country's capacity for identifying drug risks was greatly in need of repair3,4; the IOM report proposed a number of specific and plausible recommendations for reform. By coincidence, this year PDUFA is up for renewal.
For a time, it seemed possible that this combination of forces would lead to concrete steps to build a better system for drug approval and adverse-effects surveillance. But the legislative plans that are likely to be enacted do not even come close to achieving that goal. At a recent meeting on the FDA's future, all four former FDA commissioners in attendance agreed that the agency should be funded directly through the Treasury, rather than through industry payments. But Congress and the agency's leadership still don't get it. The FDA supports reauthorization of PDUFA and proposes that a trivial less than 7% of the user fees be used to strengthen its capacity for adverse-effects surveillance — an amount far short of what would be needed to repair the inadequate system described by the IOM and GAO.
Another key problem may not be fixed by Congress either. The FDA currently lacks the authority to require companies to conduct follow-up studies of suspected safety problems. Most such studies are therefore not performed, even when they are requested (see pie charts). But the requisite legislation to give the agency this vital authority also seems unlikely to emerge from this Congress.
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The present confluence of events surrounding PDUFA reauthorization could have provided the best opportunity in a generation to act decisively in mending our dysfunctional drug-approval and surveillance system. But Congress, the FDA, and the drug industry risk missing this opportunity. "The train has left the station" is how Capitol staffers describe the inevitable renewal of the plan and the rushed schedule of its legislative trajectory. But that needn't be the case. Recently, I joined a group of drug-safety experts — several of them former FDA scientists or authors of the IOM drug-safety report — in calling for the FDA's drug-related work to be funded by general federal revenues, rather than by the industry it regulates. We argued that if this change cannot be accomplished before the current user-fee act expires on September 30 (and with it the salaries of many FDA drug reviewers), then PDUFA should be renewed for 6 to 12 months at most, to give the country time to have the debate we deserve over the best way to ensure the efficacy and safety of our medications.5
Many in Congress still believe that the user-fee system is saving the public money. That view is as invalid as the smug conclusion of the hospital administrator I spoke with years ago. In regulatory policy, as in grand rounds, there's no such thing as a free lunch.
Source Information
Dr. Avorn is a professor of medicine at Harvard Medical School and chief of the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women's Hospital — both in Boston.
An interview with Dr. Avorn and Dr. Mark McClellan can be heard at www.nejm.org.
This article (10.1056/NEJMp078041) was published at www.nejm.org on April 13, 2007.
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