When there’s little proof a prescription drug will work

Millions of Americans each year are prescribed drugs that are not approved for their specific medical condition, a practice that is legal and logical in many cases. But a new study has found that fully 20% of all prescriptions are written for such nonapproved uses and that most of these -- three-quarters -- are not well-supported by scientific studies.

This widespread use of medications “off-label” could threaten patients’ safety while escaping the attention of federal regulators, some experts suggest.

“What surprised me about this study is that in many cases there is a paucity of scientific studies supporting the drug’s use off-label,” says Kenneth I. Kaitin, director of the Tufts Center for the Study of Drug Development. “It’s an issue that should be discussed in the medical community.” Still, Kaitin says, it’s unclear whether consumers are being put at undue risk. “There has not been a significant problem with off-label prescribing that I’m aware of,” he says.

The study, published last week in the Archives of Internal Medicine, polled 3,500 randomly selected doctors on all of their patient interactions over two consecutive days in 2001, including any drugs they may have prescribed. Researchers then retrieved information on the 100 most commonly prescribed drugs as well as 60 more drugs that were randomly selected.

Among other things, the scientists found that cardiac medications, anticonvulsants and asthma medications were the most likely to be prescribed off-label. Psychiatric drugs and allergy medications were the most likely types of drugs to be used off-label with little scientific support. In fact, scientific support was lacking for 96% of the psychiatric drugs prescribed off-label.

Dr. Randall S. Stafford, lead author of the study and an associate professor of medicine at the Stanford Prevention Research Center, said the findings were troubling. Even though drugs are thoroughly reviewed by the Food and Drug Administration before they’re allowed to go to market, “the FDA does not vouch for the safety and efficacy of all the various ways that drugs are used,” he says.

Drugs, he adds, are tested and approved at specific doses with detailed information about side effects that occurred during the trials -- but those data may be irrelevant when a medication is used for a different diagnosis and in different types of patients.

Off-label use of drugs is not rare. Once a drug reaches the market, doctors can legally prescribe it for any diagnosis. This long-standing practice has been lauded for allowing doctors the freedom to treat their patients based on the latest scientific studies and clinical information.

In certain areas of medicine, such as pediatrics, off-label use of medications is almost unavoidable because, until recently, drug manufacturers were not required to conduct research on how their products affect children. And in cancer treatment, off-label use allows doctors to try different strategies for seriously ill patients who have exhausted all other options.

Off-label use also makes sense when the drug is used for a condition very similar to its approved indication. For example, Stafford says, doctors can reasonably assume that a drug used to treat asthma will be effective for other lung diseases.

“There are plenty of situations where off-label use is completely legitimate,” says Stafford, “But there are other ways that drugs are used that are quite distinct from the FDA indication and where we don’t have good information.”

For example, he says, the Type 2 diabetes drug metformin is frequently prescribed for women with polycystic ovary syndrome. And gabapentin, a seizure drug, is widely prescribed for chronic pain. At the time the study was undertaken, in 2001, there was some preliminary evidence that those drugs had other beneficial uses, but it was not substantial.

However, safety issues are more likely to come to the attention of health regulators regarding an FDA-approved use of a drug than a nonapproved use, Stafford says.

The study did not address why doctors prescribe so many off-label medications bearing little scientific support. It is illegal for drug company sales representatives to promote off-label uses, although some experts think that practice occurs. (Pfizer, manufacturer of the gabapentin drug Neurontin, was convicted in 2004 for inappropriate marketing of off-label uses.)

Doctors often learn about novel drug uses from colleagues or from preliminary studies. The desire to offer patients the latest therapies may lead them to make a leap of faith with an off-label drug, Stafford says.

Consumers should ask if the prescription they receive is approved for their condition or has been adequately studied, he says. Doctors “need to think about the degree of evidence that supports what we do.”