Michael Steinman, MD -----
A review of internal documents from the pharmaceutical company Parke-Davis reveals a comprehensive and often ethically questionable campaign to market the seizure drug gabapentin to physicians, according to a paper by researchers at the San Francisco VA Medical Center and the University of California, San Francisco.
The researchers describe how Parke-Davis, a subsidiary of Pfizer Inc., sponsored consultants’ meetings, scientific research, peer-reviewed publications, and continuing medical education programs during the mid-to-late 1990s with the goal of encouraging doctors to prescribe gabapentin, including for uses and at doses for which it had not been officially approved.
“It adds up to a concerted effort to use activities that doctors commonly perceive as unbiased or scientific in order to advance marketing goals for the drug,” concludes lead author Michael Steinman, MD, a staff physician at SFVAMC and an assistant professor of medicine at UCSF. “While certain of these practices have already been disclosed, this paper provides a wide-ranging view of how scientific and educational activities were used as part of an overall strategy for drug promotion,” he adds.
The paper appears in the August 15, 2006 issue of Annals of Internal Medicine.
Documents used in the paper have been assembled by the UCSF Library as a core collection in the Drug Industry Document Archive (DIDA), which is being released online on August 15. The archive, a fully searchable record of company marketing strategy reports, internal correspondence, and descriptions of company-sponsored activities, is located at http://dida.library.ucsf.edu. Documents in the archive were obtained from public access files.
The Library is already the electronic home to a growing collection of 50,000,000 pages of tobacco company documents, known as the Tobacco Industry Document Collections, which are used by researchers worldwide to explore the operations and practices of the tobacco industry.
The Parke-Davis documents were made public as the result of a lawsuit against Parke-Davis by a former employee who alleged that the company promoted gabapentin, which it sold under the name Neurontin, for so-called off-label uses not officially approved by the FDA. Although physicians can legally prescribe a drug for any indication they feel is appropriate, off-label promotion of a drug by a manufacturer is prohibited under Federal law.
At the time the lawsuit was filed, gabapentin was officially approved only for secondary treatment of a specific form of epilepsy in teenagers and adults - a “relatively narrow indication, and thus not a huge market,” according to Steinman.
Parke-Davis promoted the drug for “pain, psychiatric conditions, migraine, and other unapproved uses,” say the authors. They note that during the 1990s, there was tremendous growth in these unapproved uses, which by the end of the decade accounted for nearly nine out of every ten prescriptions for the drug.
“There’s been an absence of internal industry documents that shed light on the process of how drugs are promoted,” Steinman notes. “These documents provide a window into how Parke-Davis went about promoting the drug, both for on-label and off-label use.”
He says the “key message” of the paper is that “much of the promotion of gabapentin occurred through educational and research programs sponsored by the drug maker and through its corporate partners.”
In such circumstances, says Steinman, “it appears that many educational and scientific activities were twisted by promotional influence and were no longer truly independent or objective. This is dangerous, since physicians may be largely unaware of the bias to which they are being exposed.”
Steinman and his colleagues identify several tactics employed by Parke-Davis in pursuit of its marketing strategy. These included hiring private companies to create continuing medical education programs consistent with marketing goals for gabapentin; sponsoring medical advisory boards and consultant meetings for which moderators and participants received honoraria and other benefits from Parke-Davis; sponsoring a large study that aimed to familiarize physicians with the idea of using gabapentin in higher-than-approved doses; discouraging the publication of research results unfavorable to Parke-Davis’s marketing goals; and sponsoring apparently independent scientific publications in the medical literature on topics that paralleled company marketing goals.
Many of these activities were organized through third-party companies paid by Parke-Davis through “unrestricted educational grants,” say the authors. While this created an aura of independence and scientific objectivity, in reality these companies had extensive ties with Parke-Davis, they say. In some cases, the same companies that developed educational programs for Parke-Davis also worked with the drug maker on strategies for marketing gabapentin.
According to Steinman, the success of these programs was “augmented by efforts to gain support from leading physicians through financial relationships and other ties.” Parke-Davis identified and targeted individual physicians who were considered opinion leaders in their fields, paid them to speak or consult on behalf of the company, and facilitated their participation in research on gabapentin, according to the authors. In developing these relationships, says Steinman, Parke-Davis sought to use these opinion leaders to disseminate favorable messages about gabapentin to their colleagues.
Steinman concludes, “The current system for separating commercial from scientific speech is inadequate. A self-regulatory approach has not worked. There are enormous loopholes through which commercial content can influence the course of medical debate.”
To address the problem, the authors call for “rigorous regulatory oversight, strict sequestration of commercial and scientific activities, and a fundamental re-evaluation of the interactions between individual physicians, professional organizations, and industry.”
The UCSF Library’s Drug Industry Document Archive site supports full-text search functions and display of PDF images, and features a special section with highlights of documents in the archive.
“DIDA continues the UCSF Library’s leadership in creating portals into new areas for research and training that shed light on the operations and practices of specific industries, in this case the pharmaceutical industry and its marketing practices,” says UCSF University Librarian Karen Butter. She notes that while DIDA was created in partnership with UCSF faculty, the archive is intended to support research not only at UCSF but throughout the world.
Co-authors of the paper are Lisa A. Bero, PhD, of UCSF, and Mary-Margaret Chren, MD, and C. Seth Landefeld, MD, of SFVAMC and UCSF. Steinman, Chren, and Landefeld served as unpaid expert witnesses on behalf of the plaintiff in the litigation that produced the core documents of the archive, and Steinman and Landefeld assisted in the creation and development of the archive.
The research was supported by funds from the Department of Veterans Affairs, the California Tobacco-Related Disease Research Programs, the National Institute on Arthritis and Musculoskeletal and Skin Diseases, the National Institute on Aging, and the John A. Hartford Foundation.
Seed funding for the Drug Industry Document Archive was provided by a gift from Thomas Greene to the University of California Board of Regents. Mr. Greene’s law firm represented the plaintiff in the litigation.
SFVAMC has the largest medical research program in the national VA system, with more than 200 research scientists, all of whom are faculty members at UCSF.
UCSF is a leading university that consistently defines health care worldwide by conducting advanced biomedical research, educating graduate students in the life sciences, and providing complex patient care.