Off -label use of pharmaceuticals is common in cancer treatment for many reasons, including targeting certain kinds of tumors. It is employed in many other medical situations as well. Yet such use raises sticky ethical questions and muddies legal liability, because clinical trials will not have shown the drug to be effective for conditions other than those for which it has been approved. Some regard off -label drug use as an unethical form of human experimentation, yet it often becomes the standard of care and may sometimes be state-of-the-art therapy.
III. Case Study
Off -label use is legal in the United States, where the practice is so widespread that some studies show that 60 percent of prescriptions in the United States are written for unapproved uses. It is mainly older, generic medicines that fall into this category because often new uses for them are found. Frequently, there is medical evidence to support the new use. But the makers of the drugs have not put them through the formal, lengthy, and often costly studies required by the U.S. Food and Drug Administration (FDA) to officially approve the drug for these new uses. Insurance companies are reluctant to pay for drugs for uses that are not FDA-approved. Reimbursement is the biggest problem with off -label drug use. Denials of payment are common because insurance companies view off -label drug use as “experimental” or “investigational.”
According to the American Cancer Society, in cancer treatment these issues have been largely addressed through 1993 federal legislation that requires coverage of medically appropriate cancer therapies. This law includes off -label uses if the treatment has been tested in careful research studies and written up in well-respected drug reference books or the medical literature. And in 2008, Medicare rules were changed to cover more off -label uses of cancer treatment drugs.
In efforts to avert drug-related public health disasters, the U.S. Congress amended the 1938 Food, Drug, and Cosmetic Act in 1962. Still in effect, the 1962 amendments require that the FDA approve new drugs coming onto the market for specific conditions. Pharmaceutical companies must specify the exact conditions for which the drug is to be used; must show its safety, efficacy, and effectiveness; and must keep marketing and promotional materials within that scope. The “fine print” required on printed pharmaceutical advertisements, the warnings that accompany broadcast advertisements, and the “patient package inserts” (or PPIs) you get at the pharmacy may mention only the approved uses. Even if the unapproved uses of the drug have become commonplace, so-called off -label uses may not be mentioned.
The FDA has been careful not to regulate the practice of medicine and has left physicians free to use their own clinical judgment in prescribing drugs. Patients who have so-called orphan diseases, those suffered by small numbers of people, almost always rely on off -label prescriptions, and cancer patients are also often prescribed drugs off -label. Even common conditions such as acne can be treated with off -label drugs. Hormonal contraceptives have been prescribed for their “side effects” in cases of severe acne because Accutane, the drug approved for acne, causes birth defects and is strictly controlled. Male and female users must certify that they are using at least two forms of contraception while on Accutane.
Although physicians may prescribe off label, pharmaceutical companies are strictly barred from marketing drugs for off -label uses and can be sued if they mention off -label uses in marketing and promotions or try to persuade physicians to prescribe drugs for unapproved conditions. A high-profile case involved Parke Davis, then a division of Warner-Lambert, maker of the antiseizure drug Neurontin, which was approved in 1994 to treat epilepsy as an “add-on” after other drugs had failed to control seizures. Parke Davis undertook a successful campaign to get physicians to prescribe Neurontin not just to reduce seizures but also for pain. This campaign made Neurontin a blockbuster drug—until a sales representative blew the whistle on the off -label marketing strategy in 1996.
It is always to a company’s financial advantage to widen the market for its products. The question that remains unsettled is when pharmaceutical companies should go back and seek FDA approval for off -label uses.
Nancy D. Campbell
- American Cancer Society, Off -Label Drug Use. Feb. 23, 2010. http://www.cancer.org/treatment/treatmentsandsideeffects/treatmenttypes/chemotherapy/off-label-drug-use
- Angell, Marcia, The Truth about the Drug Companies. New York: Random House, 2004.
- Eaton, Margaret L., and Donald Kennedy, Innovation in Medical Technology: Ethical Issues and Challenges. Baltimore: Johns Hopkins University Press, 2007.
- Loughlin, Kevin, et al., eds., The Guide to Off -Label Prescription Drugs: New Uses for FDA-Approved Prescription Drugs. New York: Free Press, 2006.
- National Cancer Institute, Understanding the Approval Process for New Cancer Treatments. http://www.cancer.gov/clinicaltrials/learningabout/approval-process-for-cancer-drugs
- United States General Accounting Office, Off -label drugs, reimbursement policies constrain physicians in their choice of cancer therapies (report GAO/PEMD-91–14). September 1991. Washington, DC. http://archive.gao.gov/d18t9/144933.pdf