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Off-label Prescriptions: Patient Protection vs Biomedical Innovation

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Image courtesy of NIH Image Bank

by Brenda Kostelecky

The serendipitous nature of scientific research is well appreciated and many drugs that were developed for one disease have later been found effective in treating other conditions. Examples of such drugs include azidothymidine (AZT), a major breakthrough in HIV/AIDS treatment that was initially developed to combat cancer, and imatinib, which was first approved for treatment of chronic myeloid leukemia and later to combat gastrointestinal stromal tumors. Exploration of additional uses for existing drugs has tremendous potential to benefit patients with conditions that currently lack quality treatments and those patients for whom traditional treatments are available but have failed. There are a number of ways to explore new drug uses, one of which is off-label drug prescriptions. Although the U.S. Food and Drug Administration (FDA) approves new drugs for very specific uses, doctors are allowed to prescribe an FDA approved drug for any additional “off-label” uses. There is some rationale for allowing doctors to prescribe drugs off-label. Patients want access to the best medicines available and doctors want to preserve all possible weapons in their treatment arsenal.

Does the practice of off-label prescribing encourage innovation of beneficial therapies while adequately protecting patients? Policymakers and the FDA continue to grapple with this question and try to ensure scientific evidence informs the use of medical products. Off-label drug use comes with serious concerns. The fact that a physician prescribes a drug conveys the message to patients that its use is scientifically supported. In fact, evidence suggests that approximately 20% of all prescriptions are written for off-label drug uses and that 73% of those uses are supported by little or no scientific evidence. One problem is that given the current speed of research, busy physicians often struggle to stay abreast of the latest available scientific evidence. Corporate motive is also a concern because off-label drug use can be lucrative for pharmaceutical companies and may pit their profits and desire to sustain future drug development efforts against patient protection.

One step the FDA has taken to limit scientifically unsupported drug prescription is to prohibit the direct marketing of drugs to doctors by pharmaceutical companies for off-label uses. Companies are, however, allowed to distribute journal articles supporting off-label drug uses to physicians. Although these articles must be peer-reviewed, they may be limited to very small patient populations, compare the drug only to a placebo when another suitable treatment is available, or be industry-sponsored. In addition, studies reporting positive findings are far more likely to be published than studies finding no effect and may give physicians the false impression that the published data is representative of all trial data.

While there is hot debate about how extensive the FDA’s role should be in both patient protection and innovation, FDA Commissioner Margaret A. Hamburg, M.D., contends that these two objectives need not be at odds with one another. Dr. Hamburg suggests that if the FDA ensures the best drugs – rather than the most effectively marketed drugs – rise to the top, innovations that can truly help patients will be promoted. One potential way the FDA could ensure doctors prescribe treatments based on evidence is to conduct comprehensive evidence analysis and regularly provide educational material to physicians on the current state of scientific research. Greater patient protection could be provided by requiring patients’ informed consent so they are aware of the risks and uncertainty regarding off-label drugs they are prescribed. Greater investment in regulatory science to develop new methods and standards could help speed development and FDA approval of quality medical advances. Some of these mechanisms could underpin a comprehensive approach addressing potential pitfalls to ensure that off-label prescription supports the FDA’s dual goals of true biomedical innovation and patient protection.


(1) Zidovudine (AZT). From Wikipedia.
(2) Imatinib. From the U.S. National Library of Medicine.
(3) Regulating Off-Label Drug Use — Rethinking the Role of the FDA. Stafford RS, N Engl J Med 2008; 358:1427-1429.
(4) Cooking the Books: The statistical games behind “off-label” prescription drug use. Sanghavi D, Slate 2009.
(5) Innovation, Regulation, and the FDA. Hamburg, MA, N Engl J Med 2010;363:2228-32.


Written by sciencepolicyforall

November 22, 2011 at 2:23 pm

Posted in Essays

Tagged with , ,

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