TCS Daily


Resuscitating FDA

By Henry I. Miller - March 8, 2005 12:00 AM

The FDA is the nation's most ubiquitous regulatory agency. It oversees products that account for twenty-five cents of every consumer dollar, with a value of over a trillion dollars annually. The agency is also a perennial favorite target of critics, who variously accuse regulators of too cozy a relationship with the drug industry or of excessive risk-aversion and delay of approvals. Then-FDA Commissioner Frank E. Young once characterized his agency as "a slow-moving target that bleeds profusely when hit."

Recent events have plunged the beleaguered FDA into turmoil. First, there were claims that the labeling of certain antidepressants failed to warn doctors that the drugs caused some adolescents to commit suicide. Then the agency was blind-sided by Chiron Corporation's inability to provide flu vaccine this season due to contamination at its manufacturing facility, depriving Americans of half the usual supply. Thereafter came questions about side effects from several widely prescribed anti-inflammatory analgesic drugs.

These events have precipitated a frenzy of attacks on the FDA. In November testimony before the Senate Finance Committee, one of FDA's medical officers accused his own colleagues of discounting recommendations from the agency's safety researchers and of consistently being in denial when data indicates safety problems from an approved drug. Senator Ted Kennedy (D-Massachusetts), the ranking Democrat on the senate committee with oversight over the FDA, called the agency's drug-safety record "a catastrophic failure."

These blanket condemnations misrepresent the reality and ignore the subtleties of drug testing, evaluation, approval and monitoring.

Shepherding a candidate drug from discovery in the lab to the marketplace typically requires 12-15 years and more than $800 million in direct and indirect costs. On average, it involves more than 60 clinical trials with more than 4,000 patients, but even this extensive testing often does not elicit all possible side effects from a new drug, especially if they occur in a vulnerable sub-population. Like death and taxes, drugs' side effects are inevitable. Their exact frequency depends, in part, on how hard one searches for them and how they are defined, but they are extremely common. In the U.K., approximately 5 percent of hospital admissions are in some way due to an adverse effect of a medicine; and between 5 and 10 percent of hospitalized patients are estimated to suffer an ADE. In one American study 6.7 percent of patients suffered serious side effects during their hospital stay.

Regulators make decisions about marketing approval on the basis of data that is always, in a sense, incomplete: Infrequent side effects, or "adverse drug experiences" (ADEs), might not show up until hundreds of thousands, or even millions, of patients are exposed to the drug in normal use. Drug companies must report to FDA adverse events and injuries caused by their products, but they depend on practicing physicians to provide these data. And because doctors are unlikely to notice side effects that occur only in a small percentage of their patient populations and are under no legal obligation to communicate adverse events at all, under-reporting is rampant.

The "safety" of a drug is a relative thing. Safety and efficacy, the two criteria required for marketing approval of a drug, are inextricably linked; regulators' judgments require a global, and often difficult, calculation of risk and benefit. Regulators and doctors tolerate greater uncertainty and more severe side effects for a potential cure for pancreatic cancer or AIDS, for example, than for treating age spots or indigestion. When FDA grants marketing approval, the drug is deemed to be safe and effective for the conditions on the label. The company and FDA painstakingly discuss the labeling, to specify uses, dosage, warnings and side effects. And at the end of the day, if FDA isn't completely satisfied, there's no label -- and no approval.

FDA is not the only gatekeeper that restricts consumers' access to prescription drugs: physicians must prescribe them and, for many Americans whose drugs are paid for by an HMO plan, the organization's formularies must include them. Going to the doctor is not like going to the supermarket, where you put in your cart whatever you want: Physicians are (or should be) used to saying no to patients who demand specific therapies. Many doctors now firmly -- and correctly -- deny patients unneeded and ineffective antibiotics for virus-caused colds, for example, and routinely do the same for other drugs.

The efficient detection of ADEs is essential, and there is a need in the United States to improve pharmacovigilance -- the monitoring of the safety of approved drugs. This should be achieved not by creating a new, independent agency, but by fixing the FDA we have. We should have learned from bitter experience the futility of regulation that focuses narrowly on "safety," to the exclusion of benefit: for example, the EPA's dangerous Superfund program and that agency's anti-consumer, anti-innovation oversight of pesticides and other chemicals.

For a start, we need to encourage physicians' reporting of side effects, perhaps by rewarding them with the Continuing Medical Education credits they need to retain licensure, to contract with organizations that treat large patient populations to monitor and report adverse events, and to share data with foreign regulators. We might also consider some variation on the U.K.'s "yellow card" system, in which doctors, dentists and pharmacists report ADEs to federal regulators (on a small, simple yellow card, of course).

We need reform of our system of drug development and its regulation, but we must ensure that the cure isn't worse than the disease.

Henry I. Miller, a physician and fellow at the Hoover Institution and Competitive Enterprise Institute, was an FDA official from 1979 to 1994. His latest book (co-authored with Gregory Conko), "The Frankenfood Myth How Protest and Politics Threaten the Biotech Revolution," was selected by Barron's as one of the 25 Best Books of 2004.
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