Manufacturers may promote off-label uses for drugs.

The FDA can't stop pharmaceutical companies from encouraging physicians to use drugs for unapproved purposes, ruled U.S. District Court Judge Royce Lamberth in July. Lamberth found unconstitutional the parts of the Food and Drug Administration Modernization Act (FDAMA) of 1998 that regulate drug manufacturers' distribution of information on off-label drug uses. (Washington Legal Foundation v. Henney, No. Civ. A 94-1306 RCL, 1999 WL 557679 (D.D.C. July 28, 1999).)

"The government, however benign its motivations, simply cannot justify a restriction of truthful nonmisleading speech on the paternalistic assumption that such restriction is necessary to protect the listener from ignorantly or inadvertently misusing the information," Lamberth wrote.

After the FDA approves a prescription drug for one ailment, doctors and researchers often find other ways to use it, and physicians are allowed to prescribe a drug for any use if it has been approved by the FDA for some purpose. Up to 50 percent of prescriptions written are for off label treatments. (Fen-phen Controversy Hints at a Larger Drug Problem, USA Today, Aug. 9, 1999, at 12A.)

Under the modernization act, the FDA could regulate promotion of off-label uses. A pharmaceutical company would need to meet certain conditions before sending journal articles on the off-label uses of its product to doctors. For example, a company would have to apply to the FDA for approval of the new application of a drug before promoting it, submit promotional materials for review by the agency before distribution, and report on promotional activities semiannually.

The Washington Legal Foundation, a nonprofit legal group, brought the suit against FDA Commissioner Jane Henney and Health and Human Services Secretary Donna Shalala in 1994. Lamberth found in summary judgment a year ago that the FDA guidelines were unconstitutional but agreed to review them after the FDAMA passed.

Ultimately, Lamberth rejected the requirements as violating the Constitution, reasoning the FDAMA had many provisions for restricting manufacturers' dissemination of medical articles, but the government did not have substantial interests to justify the restrictions. "To the extent that the policies contained in the FDAMA are premised on the FDA's goal of protecting health care providers from misusing truthful, nonmisleading information, those policies violate the First Amendment," Lamberth wrote in the decision. "The supplemental application requirement of the act amounts to a kind of constitutional blackmail."

As a result, drug companies may aggressively promote the off-label use of any product approved by the FDA.

The problem, according to Sidney Wolfe, director of Public Citizen's Health Research Group, is that physicians need balanced information about off-label uses, such as the information provided in peer-reviewed medical journals, but drug companies are not impartial providers. A manufacturer is unlikely to disseminate information that doesn't support its product, and doctors may be so busy that they rely on drug company handouts to find out about off-label uses.

The issue is "whether the distribution of favorable, out-of-context, hand-picked articles--paid for by the drug's manufacturer--should be allowed to encourage potentially dangerous prescribing of drugs for purposes that lack evidence that benefits outweigh risks," said Wolfe. (Sidney M. Wolfe, Promoting Off-Label Uses Too Risky, USA Today, Aug. 9, 1999, available at http://www.usatoday.com/news/ comment/ncoppf.htm.)

Even the FDA agrees that there are safe off-label uses for drugs, but some uses are hazardous. For example, Duract, an effective short-term painkiller, proved dangerous when prescribed beyond 10 days, which doctors routinely did. Heart drugs used to treat severe heart irregularities prescribed off-label for slight arrhythmia have caused an estimated 50,000 deaths.

In August, a Texas jury awarded $23 million to a woman who suffered heart damage after taking the off-label combination of fen-phen as a diet aid. (American Home Products Corp. v. Bernal, No. 13-99-089-CV, 1999 WL 640034 (Tex. Ct. App. Aug. 19, 1999).)

The FDA doesn't conduct research into off-label uses of drugs. The responsibility for conducting clinical tests of unapproved uses falls to private entities such as pharmaceutical companies.