- The Washington Times - Sunday, July 31, 2005

These are turbulent times for the Food and Drug Administration. The almost daily barrage of headlines questioning the safety of marketed drugs is probably depleting regulators’ stocks of aspirin and antacids. But as they try to soothe their own pain, regulators must not forget their mission: to ease the plight of patients who need new medicines.

Past criticism of FDA mostly concentrated on what arguably remains the agency’s most important shortcoming: the delays and escalating expense of getting drugs through the development pipeline and into the market. Lately, however, events have shifted the focus to safety. First there were claims certain antidepressants’ labels failed to warn doctors that the drugs caused some adolescents to commit suicide. Then the agency was blind-sided by contamination that rendered unusable half the nation’s flu vaccine last winter. Finally, there were revelations about previously unknown side effects of several widely prescribed anti-inflammatory analgesic drugs.

Regulators’ increasing sensitivity to safety may have become contagious: Drug manufacturers, too, seem to have begun to “err on the side of safety” to a degree that triggers voluntary removal from the market of safe and effective drugs.

Consider Tysabri, only the sixth medication approved — and the first in several years — for treating Multiple Sclerosis (MS), a debilitating autoimmune disease affecting the central nervous system. The stunning results of clinical trials — the frequency of clinical relapses was cut more than half — induced FDA to grant accelerated approval last fall. MS patients eagerly put their names on waiting lists for the medicine.

But this ray of hope for MS sufferers was short-lived. By the time several thousand patients were being treated with Tysabri, three confirmed cases of a rare neurological disorder caused by a virus were reported. (Because the drug suppresses certain aspects of the immune response, regulators, clinicians and the drug’s developers from the beginning were sensitive to infections as a possible side effect.)

Immediately — some say prematurely — the medicine’s manufacturers voluntarily halted production and distribution and withdrew Tysabri from the market. MS victims and many neurologists were bitterly disappointed. Now they can only hope a comprehensive review of all the clinical data — including results of new diagnostic tests on Tysabri recipients — will permit the drug’s return to the market.

The “safety” of a drug is relative. Safety and efficacy, the two criteria for marketing approval, are inextricably linked. Regulators’ judgments require a global and often difficult calculation of risk and benefit, including consideration of available alternative therapies.

We tolerate more uncertainty and severe side effects for a potential cure for pancreatic cancer or AIDS than for treating heartburn. When FDA grants marketing approval, the drug is deemed safe and effective for conditions on the label.

In the current climate of litigiousness and antipathy to big companies, one can understand the haste to withdraw Tysabri voluntarily from the market. What is also understandable (and lamentable) is the chattering classes’ hyping of the drug’s health concerns and of the stock market effects of its withdrawal, while ignoring that real people able to lead more normal lives with Tysabri now can’t get it.

Another casualty is patients’ ability, after consulting with health-care professionals, to make informed decisions about possible treatment options. That fundamental right should not be usurped by risk-averse, publicity-shy bureaucrats, anti-FDA health-care activists or members of Congress.

As more breakthrough drugs come before FDA for approval, the agency must curb its paternalistic instincts and find a way to more sensibly balance safety with patients’ right to assume responsibility for their own medical decisions. This would be a sea change for FDA, which in many areas — “off-label” prescribing, and disseminating new information about drug therapy, among others — has sought repeatedly to limit physicians’ and patients’ discretion on treatment decisions.

To this point, FDA has been even-handed on Tysabri. The clinical data justified the accelerated approval; ongoing analysis of safety data is a responsible action; and if the data support it, FDA should work with Tysabri’s producers to rapidly reintroduce the drug. Labeling restrictions, such as a prominent “black box” warning or strict limits on who can receive a drug, are “risk-management” options within FDA’s purview. In any case, FDA actions must be driven by the data.

The notion FDA should “err on the side of safety” must be qualified for patients with incurable or poorly treatable diseases: For them, there is no safety in the status quo, and they are only damaged further by paternalistic public policies that prevent them from exercising their own judgment about risks and benefits. If FDA must err, it should be on the side of patients’ freedom to choose.

Henry I. Miller, a physician and fellow at the Hoover Institution and Competitive Enterprise Institute, headed the FDA’s Office of Biotechnology from 1989-1993. His most recent book, “The Frankenfood Myth,” was chosen by Barron’s as one of the 25 Best Books of 2004.

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