One-fifth of all medications prescribed by in-office physicians are prescribed for uses not explicitly approved by the Food and Drug Administration, according to a recent study conducted by Ph.D. candidate David Radley at Dartmouth Medical School's Center for Evaluative Science. He also found that in three-fourths of those situations there was little or no scientific evidence to support the medication's usage.
The practice of prescribing off-label medications, or medications prescribed for uses not approved by the FDA, has come under increasing scrutiny in recent years. But before Radley's study physicians and legislators could only guess at the prevalence of off-label prescribing.
"Off-label uses typically lack the same degree of scientific scrutiny labeled uses receive," Radley said. "Our original motivation was to understand how frequently drugs were prescribed off-label because of the potential risk to patient safety."
In 2001 Radley and his colleagues from the Massachusetts Institute of Technology, Harvard University and Stanford University obtained data from the National Disease and Therapeutic Index, a privately-conducted survey that gathered information about patient diagnosis and drug treatment from 3,500 physicians during two consecutive work days. His team identified 160 drugs, which accounted for 725 million prescriptions and 60 percent off all drug use in 2001.
The authors established the indications for which the FDA approved each drug. After identifying all off-label prescriptions, they classified those which had strong scientific support for improving the observed condition and those that did not. There is strong scientific support, for example, in using asthma medicine to treat other lung diseases.
The study found that 21 percent of the 725 million prescriptions were off-label and of that 21 percent, 73 percent lacked scientific support. But this also means that 85 percent of the prescriptions were FDA approved for the specific indications, or that there was strong scientific support for that particular use.
"Those with strong off-label support we're really not too concerned with," Radley said. "We're concerned with that section of off-label use that really lacks scientific support."
Currently, new drugs must go through a rigorous approval process which includes numerous patient safety tests and clinical trials before they are approved for widespread use.
"The FDA regulates market entry, but remains largely hands off when it comes to treatment decisions; they let physicians choose what they feel is the most appropriate therapy," Radley said.
However, the FDA does not allow direct-to-consumer advertising -- the drug advertisements on TV or in popular magazines -- for off-label uses.
While off-label prescribing gives doctors the flexibility to develop innovative treatments and manage uncommon illnesses, this can also be a risk to patient safety, especially in populations not studied in the FDA approval process, Radley said.
"Prescription drugs are rarely tested in children. Almost all medication for children is off-label drug use. Another common population that doesn't get tested in FDA studies is women, most often pregnant women," Radley said.
Radley and his co-authors hope to expand their research on off-label prescribing by identifying waste in the American healthcare system.
"One aspect of off-label use that may be particularly relevant will be understanding the cost of an off-label drug compared to a standard on-label drug both used for the same condition. Relatively costly off-label uses should raise greater concerns regarding inefficient use of health care resources," Radley said. "It would be a question of how much extra we are spending including extra prescriptions and extra office visits."
The study was funded by the U.S. Agency for Healthcare Research and Quality and Merck and Company, Inc. In the past week Radley's research has appeared in USA today and on National Public Radio. The study was published in the May 8 issue of the Archives of Internal Medicine.
