The FDA Betrays Its Mandate

Why are so many drugs withdrawn from the marketplace after physicians realize that their patients are suffering serious, sometimes life-threatening side effects? Why aren’t these products  thoroughly tested before being sold to the public? The current issue of The New England Journal of Medicine (Sept. 6) places the blame right where it belongs—with the FDA. In “Sidelining Safety—The FDA’s Inadequate Response to the IOM”  Sheila Weiss Smith describes the Food & Drug Agency’s weak response to the  Institute of Medicine’s sharply critical report on the agency’s failure to “embrace a culture of safety.”

Smith provides an insider’s look at the FDA. An associate professor at the Center on Drugs and Public Policy at the University of Maryland’s School of Pharmacy, she  has sat on a number of FDA advisory panels. (She also served as a consultant to the IOM panel.)

From that perspective, she charges that he IOM report, which came out last September, makes it clear that the agency “is in need of monumental change: its philosophy is no longer aligned with its regulatory mandate” to ensure that risks of a drug do not outweigh the benefits.

The FDA’s response to the IOM certainly seems to confirm Smith’s diagnosis. Rather than focusing on safety issues, the FDA describes its "fundamental dilemma" as weighing the "tradeoff between safety and access.”  Here, Smith suggests, the “FDA betrays its mandate to make sure that U.S. drugs are both safe and effective . . .  The public expects the FDA to be the final arbiter of drug safety. . .  . By pitting safety directly against ‘access and innovation,’”  the agency suggests that it has two conflicting goals—making sure that the industry can get cutting-edge drugs to the market as quickly as possible, and making sure that those products will not harm the public.

Here I would suggest that it is the pharmaceutical industry, not the FDA,  that should be concerned with “access and innovation.” This is the industry’s  natural mandate. In order to grow earnings, drug-makers must constantly strive to bring new products to market., providing the access that the public wants—and deserves—to the most promising new discoveries. On the other side of the table, the FDA is charged with representing and protecting the public’s interest in safety and efficacy. There is a natural tension between these two roles—and rightly so. While the industry pushes for the swift approval that its shareholders want, the agency is expected to push back, requesting sound scientific evidence that new products have been thoroughly tested in well-designed trials.  From this dialectic of capitalism and government regulation of potentially dangerous products a balanced approval process should emerge.

Instead, the FDA seems to take the industry’s mandate as its own, “fast-tracking” drugs even when there is no crisis. As Smith points out “accelerated development programs and expedited reviews” make sense to “hasten the introduction of lifesaving drugs . . .  but they should not be an option for treatments intended for chronic conditions. Drugs designed to treat chronic diseases should have safety standards that tolerate minimal uncertainty.”  Nevertheless, the FDA has been interpreting  the 1992 Prescription Drug User Fee Act very broadly, and as a result, . “drugs for the treatment of common chronic conditions such as diabetes (troglitazone), obesity (dexfenfluramine), and pain (rofecoxib) were approved under expedited programs-- and later were withdrawn from the market for safety reasons..”  [my emphasis]

Smith also notes that “the very structure of the FDA marginalizes safety. All regulatory authority lies within the drug-evaluation divisions of the Office of New Drugs (OND) in the Center for Drug Evaluation.” Meanwhile, “the FDA's safety experts work in a separate Office of Surveillance and Epidemiology (OSE) — which is not even a part of OND — and serve only as consultants to the review divisions, having no direct regulatory authority. Although they may be asked to provide background information as context for interpreting an application, they do not regularly participate in drug reviews.”

Several IOM recommendations address “the importance of including safety experts as integral players in the drug-review process,” Smith notes. “Yet instead of undertaking a fundamental restructuring to integrate the relevant offices, the FDA merely initiated two pilot projects that involve OSE personnel in drug reviews to determine the ‘logistics and value’ of doing so.”

If the FDA doesn’t recognize the “value” of integrating safety experts into the review process, who will?

Too often, the FDA’s language reveals its skewed priorities. Responding to an IOM  recommendation that “scientists with expertise in pharmacoepidemiology or public health be included as regular members of all scientific advisory committees”  the agency replies that it would include such expertise "when safety issues are an important component of the issues before the Committee." [my emphasis]

“But safety should always be on the agenda!” Smith exclaims. Such expertise is absolutely necessary, she points out, “both to evaluating and review often sparse safety data at the time of drug approval” and to evaluate proposed postmarketing studies.

That the FDA views what it calls “safety  issues.” of only occasional interest is both shocking and alarming.