Off-label promotion of prescription drugs has become a source of substantial controversy in the past decade. Before a new drug reaches the market, its safety and efficacy must be certified by the Food and Drug Administration (FDA). But the FDA does not simply approve a drug for general use. Rather, it approves drugs for the specific uses requested by manufacturers, who choose the universe of possible indications when they undertake pre-marketing clinical trials. The approval is therefore tied to a particular disease that is the subject of the manufacturer's pre-approval testing and the FDA's formal review. The conditions for which the product is approved are spelled out in the official drug label, including the dose evaluated by the FDA, and the details of administration in which the FDA has determined the drug showed efficacy. The label also describes the safety concerns related to the use.
Once a drug is approved, however, the FDA cannot control how physicians actually prescribe it. Physicians can prescribe any drug for any medical condition, even outside of the parameters of the label, for a so-called "off-label" use. Therefore, off-label use is the prescription of a pharmaceutical product at a dose and/or for a condition that the FDA has either not reviewed or not approved. Off-label uses of drugs are commonplace. For example, most drugs historically were tested and approved for use in adults; therefore, physicians who wanted to treat similar indications in pediatric patients by definition had to use the drugs off-label.1
The practice of off-label drug use raises important public health concerns. To continue with the previous example, differences in physiology and pharmacodynamics in pediatric patients may result in far different effects in these patients than in adults.2 Recently, certain selective serotonin reuptake inhibitor (SSRI) antidepressants were linked, paradoxically, to increases in suicidal ideation in children.3 More shocking was the case of valdecoxib (Bextra), a cyclooxygenase-2 inhibitor type of non-steroidal anti-inflammatory drug that, in 2001, was submitted to the FDA for approval as a treatment for pain associated with osteoarthritis, rheumatoid arthritis, menstrual cycle pain, and acute pain.4 The FDA approved the drug for only the first three indications, rejecting acute pain as an indication because of specific dangers identified in pre-marketing trials.5 After approval, however, the drug's manufacturer engaged in off-label promotion that successfully expanded use of the product to all pain -related indications, including the one that the FDA specifically rejected.6 Therefore, off-label drug use can impose enhanced risk without proven benefit.7
In addition to individual patient risks, off-label use poses a challenge to the health care system. For example, antipsychotic drugs today are widely used off-label in elderly patients with dementia and affective disorders.8 However, a higher mortality risk has been seen in this population with the drugs in the class,9 including the newer atypical antipsychotic drugs.10 In addition, the use of antipsychotics accounts for billions of dollars in annual spending by public health insurers, the lion's share of which comes from offlabel use." Spending related to off-label use is of critical policy importance because it can raise drug costs for government payers like Medicaid- the federal- and state-sponsored health insurance program for the poor- that are already facing tight budgets.12
Current FDA regulations regarding manufacturer promotion of off-label uses weigh the rewards and risks of off-label use. Although the FDA cannot restrict physicians from prescribing drugs off-label, it does expressly forbid pharmaceutical manufacturers from promoting use of drugs for off -label purposes. While there may be some peer-reviewed evidence that an off-label use is safe and efficacious, the manufacturer has (for some reason) not submitted that evidence to the FDA for evaluation and approval. …