FDA Wants to Relax Rules — But Is This Safe for Patients?

If only we could assume that when a drug is prescribed by a doctor, there’s research showing it to be safe for that particular medical condition… but we can’t. Doctors are allowed great freedom to use drugs and medical devices “off-label,” meaning for conditions that weren’t approved for by the FDA. This can be beneficial. Or not. In fact, just last week The Wall Street Journal reported on the latest version of a story that is happening all too often. This time, a substance used to promote bone growth during spine surgery has been associated with life-threatening complications, most of which occurred with off-label use.

This situation may get even more common, as the Food and Drug Administration (FDA) has recently drafted new guidelines that may further relax the requirements drug companies must adhere to in order to market their drugs for off-label indications. Randall Stafford, MD, PhD, associate professor of medicine at Stanford University, is concerned enough about what this may mean to issue a call for public awareness and caution. He recently published an editorial on the topic in the New England Journal of Medicine, so I called him to learn more about his concerns.


Under the current FDA regulations, drug makers are not allowed to directly promote drugs for off-label use, but are allowed to distribute published literature to doctors, such as articles from medical journals about the off-label use of a drug. Those articles are supposed to have been submitted for FDA review and the companies are supposed to be pursuing formal FDA approval for the new use… but (partially due to a lack of resources) the agency is notoriously lax in enforcing this requirement. The new requirements would be only that the distributed articles come from a peer-reviewed medical journal not influenced by the company and contain no false or misleading information.

It’s not that the practice of off-label use for drugs is always dangerous — sometimes it isn’t, but sometimes it is. Dr. Stafford acknowledges that off-label prescribing “permits innovation in clinical practice, particularly when approved treatments have failed. It also offers patients and physicians earlier access to potentially valuable medications and allows physicians to adopt new practices based on emerging evidence.” His concern lies with the fact that all drugs can have what he calls “expected and unexpected risks, whether used for approved or unapproved clinical conditions.” While some off-label uses are well-studied, most are not, he told me.


In his 2006 study of off-label prescribing of 160 common drugs published in the Archives of Internal Medicine, Dr. Stafford found that off-label use accounted for 21% of all prescriptions — fully 73% of these with little or no scientific support behind them. Drugs approved for depression, schizophrenia and seizures were most likely to be used off-label for treatment of bipolar disorder, dementia and chronic pain, respectively.

Dr. Stafford notes that there is good supporting research for the off-label use of aspirin for heart disease prevention, for example. But he says there are many more instances where drugs are prescribed off-label without such evidence… or even in the face of clear dangers. For instance, he cites the growing use of atypical antipsychotic medications such as quetiapine (Seroquel) for dementia — there is limited evidence of benefit and known risk of harm, including death, when this drug is used by the elderly, said Dr. Stafford.

Alarmingly, the fact that some physicians rely solely on drug companies for education about new drugs and information on new uses for old ones means they may not even realize they are prescribing a drug that hasn’t been FDA-approved for that condition. Dr. Stafford voices concern that reducing restrictions on off-label promotion increases the likelihood that “the distinction between on-label and off-label uses will continue to be blurred for many physicians.”


What can you do? Be careful and develop a healthy skepticism. Let your doctor know of your concerns on this topic. If a new medication is prescribed to you for an off-label use, ask him/her to provide safety and efficacy information for your particular medical condition. You can do your own research, too — well-respected independent organizations and government agencies have developed guidelines that help define the best drugs to use and most publish consumer-oriented materials. MedlinePlus is a useful resource for this purpose. The more you know about the medications you take, the better.