The FDA is the nation’s most ubiquitous and influential regulatory agency. It oversees products that account for 25 cents of every dollar spent by consumers in the U.S.–over a trillion dollars annually. Because its oversight of drugs makes the agency a gatekeeper between manufacturers and the marketplace, it is essential that it operate with efficiency and a genuine commitment to making medicines available to patients who need them.
That ideal is far from the reality. Instead, we have an agency that has been leaderless and struggling for most of the past six years, and whose culture of risk-aversion puts all Americans at risk.
Drug R&D is becoming more difficult. The costs have skyrocketed, with the direct and indirect expense of bringing an average drug to market now exceeding $800 million. And there are other ominous trends:
‐ Longer clinical testing is extending the time it takes to bring new prescription drugs to market; new medicines that gained FDA approval from 2002-2004 required an average of 8.5 years to move through the clinical trials and approval phases, as compared to 7.2 years in 1999-2001.
‐Only 58 new drugs from 2002-2004 received marketing approval–a 47 percent decline from the peak of 110 from 1996-1998.
‐The number of applications to the FDA for marketing approval has been decreasing steadily since 1995.
‐Fewer than one in three drugs that are approved for marketing ever recoup their development costs.
FDA reviewers are conditioned to be risk-averse. As former FDA General Counsel Peter Barton Hutt has observed, “FDA employees have been praised only for refusing to approve a new drug, not for making a courageous judgment to approve a new drug that has in fact helped patients and advanced the public health.” His views are echoed by former FDA Commissioner Alexander Schmidt: “In all our FDA history, we are unable to find a single instance where a Congressional committee investigated the failure of FDA to approve a new drug. But the times when hearings have been held to criticize our approval of a new drug have been so frequent that we have not been able to count them. The message to FDA staff could not be clearer.”
As a result, regulators have become fearful of taking risks. They make decisions defensively, at the cost of denying to patients new drugs that can cure diseases and save lives. And they tend to delay or reject products of all sorts, from fat substitutes to vaccines to painkillers. That’s bad for public health and limits the options available to consumers.
A phrase that one commonly hears among FDA-watchers these days is that the agency lacks “adult supervision.” The agency has had a confirmed head for less than 20 months of the last six years, “a clear signal that FDA doesn’t matter much to the people who are running the country, and it can’t help but affect morale,” according to Donald Kennedy, former FDA commissioner and former president of Stanford University.
Acting FDA Commissioner Dr. Andrew von Eschenbach recently was nominated to fill the position permanently. One current senior FDA official said about him: “He is smart and pays attention. . . [but] I have the strong impression that no one is running FDA, and that even if anyone were, no one is running HHS and so nothing remotely controversial, which seems to include any decision on anything that hasn’t been decided before, can get done.”
Two Democratic senators have promised to block Dr. von Eschenbach’s confirmation indefinitely; and, in the absence of a permanent agency head, the next echelon of managers is especially critical. Dr. Janet Woodcock, the FDA’s deputy commissioner for operations, has been in a position to prevent or correct the agency’s deficiencies for more than a decade. Appointed in 1994 to head the FDA’s Center for Drug Evaluation and Research (CDER), which oversees industry’s testing of new drug candidates, sanctions their marketing, and monitors them after they are approved, Dr. Woodcock was promoted several years ago to deputy director of operations for the entire FDA. While she is a person of prodigious intelligence and knowledge, far too much has slipped through the bureaucratic cracks on her lengthy watch.
FDA Deputy Commissioner for Medical and Scientific Affairs Scott Gottlieb seems to have become the agency’s public face, frequently giving talks and granting interviews. But Dr. Gottlieb has never occupied a line position at a regulatory agency or reviewed or approved a single drug, medical device, or food product. “The [Gottlieb] appointment [came] out of nowhere. I’ve never seen anything like that,” said former Commissioner Kennedy.
It is not surprising, therefore, that in spite of good intentions Dr. Gottlieb misunderstands the FDA’s responsibility for the astronomical costs and harmful delays of drug development. “If we could develop better science, there could potentially be smaller trials” and lower costs, according to Dr. Gottlieb. Another of his remedies– ostensibly to speed the approval of generic drugs–is the imposition of “user fees,” another name for a discriminatory tax on a single corporate sector. Such fees have been in place for brand-name drugs for almost 15 years, and we’ve seen how well they’ve spurred drug development. All we have to show for them are the negative trends described above, to say nothing of increased development costs eventually passed along to patients.
What we need is not “better science” or new taxes on drug development but better management by senior officials at the FDA and discipline in the ranks. For example, in just the past few years, FDA officials have arbitrarily and unexpectedly directed clinical investigators to begin trials at inappropriately low dosages; they have limited approval of Phase 1 studies only to single-dose, instead of dose-ranging, studies; they have demanded unnecessary, invasive procedures on patients; they have required that foreign trials be completed and the results submitted before the U.S. trials could begin; they have introduced questionable warnings on labels; and they have required an excessive number of post-marketing studies.
This culture of unnecessary risk-aversion must somehow be changed, but several generations of feckless FDA leadership have been unable to accomplish it. I wish Dr. von Eschenbach luck–he’ll need it.
–Henry I. Miller, a physician and fellow at the Hoover Institution, headed the FDA’s Office of Biotechnology from 1989 to 1993. Barron’s selected his most recent book, The Frankenfood Myth… one of the 25 Best Books of 2004.