The Curious Case of Off-Label Use

Abstract

In United States, new drugs and devices cannot be marketed until Food and Drug Administration finds that they are safe and effective for their intended use. To obtain FDA approval, pharmaceutical and device manufacturers must submit extensive animal, in vitro, and human study data demonstrating safety and effectiveness. Agency staff members--often joined by an external interdisciplinary advisory committee--review research reports to evaluate quality of data and make essential risk-benefit judgments that determine whether a medical product is safe and effective. Drug and device companies spend many years and millions of dollars preparing data required for FDA approval. Although agency review process is imperfect, it does ensure that a company's claims about its product are closely scrutinized by independent scientists, physicians, and patient representatives. Safety is evaluated in light of product's specific purpose: Are therapeutic benefits valuable enough and likely enough to justify known risks posed by product? Effectiveness, too, is determined in light of product's specific purpose: Does it have desired impact on enough people with condition at which it is aimed? When FDA approves a product, officials approve a specific label for product, too. That label must contain detailed scientific information about product, including approved indications, dosage and method of administration, and use in specific populations. This rigorous and fine-grained regulatory approach to product evaluation is circumscribed, however. When Congress created FDA, members said that they did not intend for agency to regulate practice of medicine. Thus, FDA oversees only product manufacturers and commercial activities. This general regulatory stance explains curious case of off-label use. After FDA approves a drug or device for its intended use, physicians and other authorized practitioners may prescribe product for uses not covered by approved label. The FDA severely restricts manufacturers' freedom to promote products for unapproved uses. Companies that want to expand formally approved uses for their products must submit safety and effectiveness data and secure FDA approval for new uses. But FDA takes a hands-off approach to clinicians prescribing products for unapproved uses. As a result, drugs and devices are prescribed in circumstances not covered by initial product evaluation. Off-label prescribing occurs not just clinicians give products to people with conditions not listed on approved label, but they depart from approved drug dosage, method of administration, or patient population. Unapproved product combinations, such as using two different drugs to treat a single condition, are another form of off-label prescribing. Surveys show that off-label prescribing occurs routinely. For example, a study published last year examined prescribing practices for 169 commonly used drugs. Researchers found that about 21 percent were prescribed to patients with diagnoses other than those included on label. Off-label prescriptions were relatively common for cardiac drugs (46 percent), anticonvulsant drugs (46 percent), and asthma medications (42 percent). Researchers also found that about 15 percent of all drugs were prescribed for off-label uses with little or no scientific support. For some types of drugs, figures were unusually high. For example, 96 percent of off-label prescriptions for psychiatric drugs and 89 percent of those for allergy drugs were based on limited or no scientific evidence. (1) The Debate over Current Policy The FDA's hands-off approach to off-label prescribing has many supporters. One is American Medical Association, which says approach respects the autonomous clinical decision-making of a physician. Off-label use is defensible, according to AMA, when such use is based upon sound scientific evidence and sound medical opinion. …