Thursday, January 22, 2009

The "Neurontin Legacy"

The January 8, 2009 issue of the New England Journal of Medicine includes an article by Landefeld and Steinman called “The Neurontin legacy – marketing through misinformation and manipulation”[1] that should be required reading for every physician, medical student, and hospital or health facility administrator, not to mention students of, and those involved in implementing, health policy. Neurontin, the brand name for the drug gabapentin, was approved by the FDA only for adjunctive (meaning “in addition to first-line drugs”) treatment of epilepsy, but was heavily (and illegally) marketed by the manufacturer (Parke-Davis, a division of Warner-Lambert, purchased by Pfizer in 2000) for a variety of other indications including first-line treatment of epilepsy and, more importantly, pain relief, especially “neuropathic” pain – pain that arises from problems in the nerves themselves, commonly in people with diabetes.

The article notes that in May, 2004, “Warner-Lambert agreed to plead guilty and to pay more than $430 million to resolve criminal charges and civil liabilities. A class-action suit was filed the next day in federal court on behalf of private parties who had paid for illegally marketed Neurontin.” This is an extraordinary settlement, and quite appropriate given the fantastic series of marketing “tactics” that “…included education, publications, and research whose promotional intent was disguised, in addition to more transparent activities, such as advertising and sales visits.” It is illegal to market for non-FDA-approved indications, but Parke-Davis did it both incredibly aggressively and effectively, with Neurontin’s sales rising from $98 million in 1995 to nearly $3 billion in 2004. The company commissioned “research” to show the drug’s effectiveness, suppressed publication of studies that showed it had no effect on neuropathic pain, and in the words of epidemiologist Kay Dickersin, who performed a “recently unsealed 318-page analysis of research sponsored by Parke-Davis…concluded that available documents demonstrate ‘a remarkable assemblage of evidence of reporting biases that amount to outright deception of the biomedical community, and suppression of the scientific truth…’” It is worthy of note that the exposure of the Neurontin affair was the result of the efforts, almost worthy of being called heroism, of a young biologist who named David Franklin who worked for Parke-Davis.

What is the importance of this scandal? Is it that thousands of people were treated with a drug that was neither FDA approved for the indications for which it was being promoted, and may have been ineffective? Perhaps, although there are many physicians who would continue to argue that, at least in their anecdotal experience, gabapentin is effective for neuropathic pain. Or is it that pharmaceutical companies use aggressive and unethical, bordering upon and sometimes crossing the line into illegal, tactics to promote the use of their products and thus the enormous profits that accrue? Perhaps, but anyone who did not know this has long been deceiving themselves. The pharmaceutical industry has been for many years either the #1 or #1 most profitable industry in the US. The $430 million fine, while significant, is a small part of the profits that Parke-Davis/Warner-Lambert/Pfizer made through the off-label use of the drug. Is it that the court cases involving Neurontin involved the release of enormous numbers of papers (including the Dickersin report mentioned above, as well as internal company documents) that clearly demonstrate the invidious nature of pharmaceutical company promotion? If anyone needed more evidence, it is there. “Promotion,” write Landefeld and Steinman, “was neither discrete, compartmentalized, nor readily apparent; instead, it was intercalated in nearly every aspect of physicians’ professional lives, from the accoutrements of practice to lectures, professional meetings, and publications. Although some pharmaceutical marketing may be less opaque, deceptive and manipulative, evidence indicates that drug promotion can corrupt the science, teaching and practice of medicine.”

If David Franklin is the hero in this episode, the villains, in this particular case and overall in drug marketing, are the pharmaceutical companies who are willing to use any tactics to increase their enormous profits. The victims are clearly the patients who paid more for drugs that may have been ineffective, or no more effective than less expensive drugs (and, from their perspective in their class-action suit, the insurers who paid for these drugs). The facilitators, however, are the physicians who were too willing to take their information (as well as gifts, sometimes small, sometimes large) from pharmaceutical company representatives), rather than more reputable sources, and not pay attention to the principles of conservative prescribing (rule #1: use the drugs that we know are safe and work, be cautious of new “miracle drugs”). They are also certainly medical organizations, the paid physician flaks who gave the talks, and even the medical journals that uncritically published some of the company written studies. They are also, however, sometimes the patients themselves, living in a culture of NEW! BETTER! IMPROVED!, of Technology over All, who frequently beseech their physicians for something new, more effective, especially with regard to pain relief.

We have met the enemy, and it is them. But, in the words of the immortal Pogo (Walt Kelly) it is also us. If they did before (and a frightening number did!) no physician should now have any business trusting pharmaceutical companies to be completely honest, nor believe that they owe use of new drugs to the “nice men and women” who are the drug reps, nor that drug samples (always, only the newest, most expensive drugs, never the old “standbys” or certainly anything available generically) are “free”, nor most of all believe that they are not affected by advertising and gifts. All physicians and students should read not only this piece but the classic “A Social Science Perspective on Gifts to Physicians from Industry”[2] to understand the sublimal efficacy of these tactics. And patients (the medical word for “people”) need to recognize this too, and demand not “new”, but “best”, defined as well-established, effective, and safe.

[1] Landefeld CS and Steinman MA, “The Neurontin legacy – marketing through misinformation and manipulation, NEJM Jan 8, 2009; 360(2):103-05
[2] Dana J, Loewenstein G, “A social science perspective on gifts to physicians from industry”, JAMA July 9, 2003;290(2):252-5.

1 comment:

Maria said...

Thanks for this

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