Off-label drug promotion: Reform, regulation and the FDA

Off-label prescribing of prescription drugs is an integral part of clinical practice but is also highly contentious. Manufacturers seek latitude to inform physicians about the broadest range of uses of their products. The Food and Drug Administration (FDA) seeks to control claims of clinical effectiveness and safety that it has not fully vetted. A series of legal and regulatory steps over the past ten years have addressed the issue, but the contours of acceptable practice remain murkier than ever. When it approves a drug, the FDA limits marketing to those uses for which the drug has been approved and that are set forth on its label. However, once a drug is on the market, physicians may prescribe it for any purpose. These off-label uses represent 20 percent of all pharmaceutical sales and close to 50 percent for some drugs. Some of these uses are essential to clinical practice, however others are highly speculative. The Food and Drug Modernization Act of 1997 (FDAMA) set standards for acceptable promotion activities, but enforcement of these rules was restricted by a federal court decision based on free speech concerns. In response, the FDA issued guidance to manufacturers that encouraged them to adhere to strict limits. These guidelines expired with the expiration of FDAMA in 2006. In the waning days of the Bush administration, the FDA updated its rules to permit more flexibility in off-label promotion. The response of the Obama administration has not yet been determined. This presentation will review the state of the law and the new FDA regulations and will evaluate major reform options according to several dimensions. The dimensions include legal constraints, political feasibility, implementation issues, clinical needs, and enforcement effectiveness. The proposed reforms include requiring manufacturers to initiate formal clinical testing of all off-label uses that they promote, requiring prior FDA approval of all off-label promotion materials, requiring balanced presentation of positive and negative findings concerning off-label uses, and, at the other extreme, permitting broad dissemination of off-label information. Based on this review, a proposal for major reform will be presented that considers regulatory, patent, legal, and policy issues.