MONDAY, Aug. 14, 2006 (HealthDay News) -- Drug companies often influence physicians' prescribing practices without the doctors even knowing it, a new report contends.
"A lot of strategies are quite subtle, but because they are so pervasive, they really add up," said Dr. Michael Steinman, a staff physician with the San Francisco Veterans Affairs Medical Center and lead author of a paper that details the marketing activities of Pfizer Inc. on behalf of its drug gabapentin (Neurontin).
The drug was originally approved by the U.S. Food and Drug Administration in 1993 for the treatment of "partial complex seizures" involved in epilepsy. By the mid-to-late 1990s, however, it was widely used off-label for psychiatric conditions and pain.
Although gabapentin was eventually approved for one pain indication, Pfizer subsidiary Warner-Lambert settled litigation in 2004, admitting it had violated federal regulations by promoting the drug for pain, psychiatric conditions, migraine and other unapproved uses.
The court case gave Steinman and his colleagues an unusual opportunity to review about 8,000 pages of documents -- including internal correspondence and reports, presentations, transcripts and depositions -- that covered a period during which gabapentin was still only approved for treating epilepsy.
Their review is published in the Aug. 15 issue of the Annals of Internal Medicine.
"A lot of the marketing was related to off-label use, but the issue we were trying to frame wasn't so much on-label versus off-label but the sorts of marketing strategies used to promote drugs regardless of what the labeling was," Steinman explained.
The marketing often had the twin purposes, Steinman said -- influencing physicians to write more prescriptions for the drug without realizing they were being influenced.
"A lot of the strategies that were used to promote this drug were activities that doctors might not recognize as promotional at all," Steinman said. "The real danger is that doctors are being marketed to without their even knowing it. You don't know that the material should be taken with a grain of salt, and this might adversely impact the way you prescribe."
In 1998, the company had a $40 million advertising and promotion budget for the drug. From 1996 through 1998, "professional education" accounted for half to two-thirds of the budget, according to the study.
As part of this push, company officials identified physicians who were already frequent prescribers of anticonvulsants and further categorized them by the dollar value of anti-convulsant prescriptions they had the potential to generate.
Another targeted group was doctors who had the potential to influence gabapentin use among colleagues. Some doctors were recruited and trained to serve as speakers in "peer-to-peer selling" programs. Others were "thought leaders" or "movers and shakers," influential doctors affiliated with major medical centers. Some "thought leaders" requested or were allocated $10,250 to $158,250 in honoraria, research grants or educational grants between 1993 and 1997, according to the study.
The company also sponsored continuing medical education programs for doctors that appeared to be thinly veiled attempts to influence prescribing patterns, the study authors said.
"A lot of continuing medical education in this country now is run by medical education companies that are funded through unrestricted educational grants from drug companies," Steinman said. "Unrestricted means no-strings-attached, but we found that some of the same companies that are putting on medical education programs are also working for drug companies in different ways. There's an intrinsic conflict of interest. They're supposedly doing an objective program, but, at the same time, they're telling the company how they can increase sales."
Clinical trials could also have a hidden agenda, the study authors said. In one example they cited, 700 physicians were enlisted to participate in an uncontrolled, open-label trial of gabapentin in which they were instructed to increase the dose until patients were seizure-free or until a maximum of twice the FDA-approved limit was reached. The physicians enrolled an average of three patients each and were paid $300 per patient.
The question the study authors raised is, how can doctors negotiate this tricky terrain if they don't know how tricky it is?
"I don't have an easy answer," Steinman said. "It's become very hard to know where bias exists anymore, because the bright line between what is promotion and what is objective has become quite blurred, but it's not apparent that it's blurred."
"Most physicians are doing what they think is right, and the drug industry is not evil," Steinman added.
"The problem is that the reach of the drug industry is so deeply embedded into all aspects of the daily practice of medicine that it's really become quite hard to separate out what is promotional and what's not," he said. "The absence of a clear demarcation really puts us at great risk of prescribing either suboptimally for care of patients or in an excessively expensive way, which harms the health-care system as a whole."
However, Pfizer spokesman Bryant Haskins said, "Pfizer promotes all medications and provides medical education grants in
accordance with standard guidelines established by FDA and the American
Medical Association among others."
He continued, "As with all of our medications, our FDA-approved label dictates what physicians may say about our medications when physicians are speaking on behalf of the company. When physicians are acting as advisors, it is to provide clinical experience/expert opinion in the development of
clinical trial protocols or educational information."
Dr. Mark Fendrick, a professor of internal medicine at the University of Michigan School of Medicine, noted, "Ultimately, it comes back into the hands of practitioners. It's extraordinarily important for physicians to understand that it's ultimately up to them to be able to weigh the risks and benefits of every intervention they do. They can say no."
The details in the paper recall a recent move by the Journal of the American Medical Association (JAMA) to tighten its conflict-of-interest policy in response to scientists' failure to disclose all financial ties to pharmaceutical companies, Fendrick added. JAMA is not the only medical journal to have had such problems in recent months.
More information
SourceWatch has more on off-label prescribing.
