An expensive clotting drug approved to treat only hemophilia has become extremely popular in hospitals to stem bleeding during heart surgery, brain hemorrhages, trauma, liver transplants, and prostate removal. Yet a massive new analysis of 64 studies of these “off label” uses of the drug, recombinant factor VIIa (rFVIIa), has found no evidence that it prolongs life and, in some cases, it causes dangerous embolisms. “The stakes are high here in terms of patient outcome and costs,” says study leader Veronica Yank, a clinician at Stanford University in Palo Alto, California, who specializes in prevention research.
In a second paper, Yank and her colleagues showed that in U.S. hospitals in 2008, 97% of the use of rFVIIa, which costs $10,000 a dose and is made by Novo Nordisk of Bagsværd, Denmark, was off-label. It's legal for physicians to prescribe drugs off-label, but Jerry Avorn, a clinician at Brigham and Women’s Hospital in Boston, who co-wrote an accompanying editorial, says hospitals have a responsibility to act on these findings. And if they don’t? “If I were a liability attorney, I’d find that interesting,” Avorn says.
The U.S. Food and Drug Administration approved rFVIIa in 1999 as an “orphan drug” for use in hemophiliacs who had developed immune responses against other, more common blood-clotting factors already available. Surgeons soon began using it in many different settings, including combat, with little evidence of efficacy. Several studies warned about the widespread off-label use of the drug, but none was as comprehensive as the two new papers, which will be published tomorrow in Annals of Internal Medicine.
As Avorn notes in his editorial, there is "reason to wonder how the use of an obscure recombinant coagulation factor marketed exclusively to hematologists became used so widely." Novo Nordisk officials have denied that they have improperly promoted off-label use of rFVIIa, but concerns about “financial arrangements” between the company and the U.S. Army led the Department of Defense to launch an investigation in January 2010 that is still under way. Company officials insisted in a February 2010 conference call with stock analysts that U.S. Army doctors used the drug at their own discretion and that "we’ve not been marketing the product to the Department of Defense." Avorn says he has no direct knowledge of the company's marketing practices. "But I do think it’s useful that the question has been raised as to how this came to be such a popular approach,” he says.