The FDA's New Guidance for Off-Label Promotion Is Only a Start.

nosis or treatment of delineated symptoms, conditions, and diseases for which a drug is indicated. Although marketing ma terials are not permitted to promote additional uses, physicians are free to prescribe any approved drug for any pur pose, even a use that the FDA has not approved. With a sizable share of the po tential market at stake, the incentive for manufacturers to promote un approved indications is substantial. In 1997, Congress included standards for off-label promotion in the Food and Drug Administration Modernization Act (FDAMA). This act allowed manufacturers to distribute copies of peerreviewed articles and book chapters and to sponsor independent continuing medical education programs describing uses of products beyond the approved indica tions.4 There were two important conditions: (1) the materials had to be provided to the FDA, and (2) the manufacturer had to verify its plans to seek approval for the new indications. In 1998, however, the federal district court for the District of Columbia prohibited the FDA from enforcing the additional conditions in the case of Washington Legal Foundation v. Friedman on the grounds that they infringed on free speech rights.5 In response to the court ruling, the FDA issued regulations adopting the FDAMA standards as a “safe harbor” against prosecution.6 Under this ap proach, failure to comply is not necessarily a violation, but strict compliance guarantees immunity from prosecution for engaging in false or misleading adver tising. Since then, numerous enforcement actions have been brought against drug companies for overstepping the bounds of legitimate off-label promotion, including one action that led to a $30 million fine against Pfizer over its marketing of gabapentin (Neurontin).7 In 2006, a psychiatrist was arrested and charged with accepting more than $100,000 from Jazz Pharmaceuticals for promoting offlabel uses of gamma hydroxybutyrate (Xyrem), a product that had been approved to treat narcolepsy.8 FDAMA’s limitations on off-label promotion expired on September 30, 2006, and Congress has yet to reauth orize them. The FDA’s draft guidance is an attempt to fill the void. The agency continues to require that materials be re printed from bona fide independent peerreviewed sources, but it omits mandates for prior agency approval and for manufacturers to verify their intent to conduct clinical trials of unapproved uses. However, it adds two important stipulations: (1) the lack of approval of the indications in question must be clearly disclosed, and (2) if any published findings in the peer-reviewed literature contradict the efficacy of a drug’s off-label use, an article reflecting that conclusion must be distributed as well.