DOCTORS RIGHTLY treasure the freedom to prescribe a drug for purposes beyond those sanctioned by the Food and Drug Administration. But something’s gone awry in the drug-approval system when so-called “off-label’’ uses begin to predominate — especially in cases where there’s little evidence of the drug’s efficacy.
The FDA evaluates all prescription drugs before they enter the US market. But doctors often prescribe a given drug for use in populations, such as children or pregnant women, on which its effect wasn’t tested, or against diseases it wasn’t initially intended to treat. Among the most popular drugs an estimated 20 percent of prescriptions are off-label. In oncology, the figure is thought to be much higher, at 50 to 75 percent of all prescriptions. According to the Tufts Center for the Study of Drug Development, for 22 expensive cancer therapies — so-called monoclonal antibodies — off-label uses outnumber FDA-approved uses two-to-one.
These uses are often justified. It can take years to prove that a drug designed for disease A is also helpful for disease B, even after some medical evidence surfaces in favor of the new use. Patients with cancer and other life-threatening diseases may have little time to lose.
But those benefits need to be measured against the health and economic consequences of prescription practices that are backed by little medical evidence. In 2006, one landmark study found that 73 percent of off-label uses among the most commonly prescribed drugs lacked good scientific support. But once off-label uses become standard practice, manufacturers have little reason to sponsor clinical studies testing whether their drugs actually work in those unproven settings.
The federal stimulus law appropriated $1.1 billion to support research that compares treatments that have not been rigorously studied side-by-side. Given the prevalence of off-label prescription in some diseases — for example, several brands of schizophrenia drugs are commonly prescribed off-label for depression — Washington must fund studies evaluating whether any of these off-label uses are warranted. The government — not to mention insurers and employers — could help patients and save millions of health care dollars not just by identifying ineffective uses, but also by validating those that do help.