Newsweek's Mary Charmichael reported today in an article entitled "Phizer's Headache: Lawsuit charges drugmaker was deceptive about Neurontin":
After it paid $430 million to settle a 2004 lawsuit over illegal promotion of its anti-seizure drug Neurontin, Pfizer, the world's largest pharmaceutical company, may have thought its legal troubles with that medication were over. Not so fast: A new lawsuit, brought by the same attorney, alleges that the company's misdeeds went much further than originally charged. According to newly unsealed court documents, not only did the company and its subsidiaries push Neurontin for unapproved uses--the practice at the center of the first suit, which Pfizer admitted to as part of its settlement--they did so knowing that the drug was ineffective for several of those conditions (the settlement involved allegations of both criminal and civil violations). Pfizer, according to the documents, engaged in "outright deception of the biomedical community, and suppression of scientific truth"--stalling or stopping the publication of negative study results; manipulating both trial designs and data to make the drug look more effective than it was; and using questionable tactics to enhance the drug's image and increase its sales.(http://www.newsweek.com/id/162906)
Charmichael thoroughly describes the details of the charges and the current evidence against Pfizer in this case. Examples of bad research by Pfizer were presented by such credible authorities as John Abramson of Harvard Medical School, Dr. Douglas McCrory of Duke University, Nicholas Jewell of University of California at Berkeley and several others. The problems with Pfizer's research included unblinded studies, non-random sampling, lack of controls, negative studies written up to sound positive, and "cherry-picking results."
The problems with Neurontin began almost right away. The Food and Drug Administration (FDA) approved the drug in 1994 as a medication for treating partial seizures. It was effective only when added to the regimen with other anti-seizure medications. That partial effectiveness is not all bad. Some sets of medications work like that. For example a combination of acetaminophen, aspirin, and caffeine can be very effective for controlling headache pain when each medication on its own would not help. Acetaminophen, aspirin, and caffeine each are useful on their own for other ailments. Also, with methicillin-resistant staphylococcus aureus infections (MRSA), a combination of gentamicin and vancomycin may be used, or some other combination. Gentamicin and vancomycin each on their own are useful antibiotics for other infections.
The drug was designed to mimic the shape and thus function of gamma-aminobutyric acid (GABA) in the central nervous system. GABA is a neurtoransmitter between nerves and muscles and therefore its implication in movement disorders, epilepsy, and spasticity associated with some diseases was likely. GABA levels or malfunction of GABA receptors were also suspected to contribute to anxiety and schizophrenia.
In 2002 the FDA approved Neurontin for treatment of another condition, a very specific ailment, postherpetic neuralgia. After that, the drug was used for "off-llabel" ailments including migraine headaches, neuropathy, nystagmus, bipolar affective disorder, anxiety, obsessive-compulsive disorder, insomnia. Other uses included muscle spasms in multiple sclerosis, "complex regional pain syndrome," "postoperative chronic pain," hot flashes and tinnitus. (http://en.wikipedia.org/wiki/Gabapentin).
However, more recently, several larger, controlled, and double-blind studies have found that gabapentin was no more effective (and in one study, slightly less effective) than placebo. They cite Pande, AC; Crockatt JG, Janney CA, Werth JL, Tsaroucha G. (2000). "Gabapentin in bipolar disorder: a placebo-controlled trial of adjunctive therapy" (Abstract). Bipolar Disorders 2 (3 Pt 2): 249–55. doi:10.1034/j.1399-5618.2000.20305.x. PMID 11249802. Retrieved on 2006-08-14. (http://en.wikipedia.org/wiki/Gabapentin)
How did a narrow usefulness for a medication grow into usefulness for so many ailments? Marketing. In the time frame when Pfizer and Park-Davis were marketing this drug and others, it was common practice for drug reps to schedule appointments in doctors' offices and spend loads of money on extravagant buffet lunches (lunch time was the only time doctors and their staff were able to take a breather and listen, so drug reps bought lunch and the offices were willing to listen to the spiel). Lots of free goodies such as notepads, pens, keychains, and gadgets would be showered on the office staff. Massive quantities of free samples of the medication would be dropped off so doctors could not only help patients save money on prescriptions, but also report back on the effectiveness of the medication, and most important, prescribe the medication to more and more patients. Physicians and ancillary medical personnel were paid by drug companies to attend seminars promoting their products. Just for showing up and listing, a person could get $500 cash or more. Nobody likes to bite the hand that feeds them and so good will between drug reps and physicians encouraged the use and prescription of Neurontin and other medications.
Neurontin is one of Pfizer's best-selling drugs, and was one of the 50 most-prescribed drugs in the United States in 2003. However, in recent years, Pfizer has come under heavy criticism for its marketing of Neurontin, facing allegations that, behind the scenes, Parke-Davis marketed the drug for at least a dozen supposed uses for which the drug had not been FDA approved.
By some estimates, so-called off-label prescriptions account for roughly 90% of Neurontin sales. While off-label prescriptions are common for a number of drugs and are perfectly legal (if not always appropriate), marketing of off-label uses of a drug is strictly illegal. In 2004, Warner-Lambert agreed to plead guilty and pay $430 million in fines to settle civil and criminal charges regarding the illegal marketing of Neurontin for off-label purposes, and further legal action is pending. The courts of New York State, for example, have refused to certify a class of injured parties who took Neurontin for off-label use, finding that they had failed to state that they had any injury.
The University of California, San Francisco (UCSF) has archived and studied the documents made public by this case, which opens a unique window into pharmaceutical marketing and their illegal promotion. However, Pfizer maintains that the illegal activity originated in 1996, well before it acquired Parke-Davis (through its acquisition of Warner-Lambert) in 2000. Several lawsuits are underway after people prescribed gabapentin for off-label treatment of bipolar disorder attempted or committed suicide. (http://en.wikipedia.org/wiki/Gabapentin)
The American College of Physicians has an excellent website that details the current laws regarding pharmaceutical marketing and promotion. They write:
In 2005, twenty eight states (AR, CA, CT, FL, HI, IL, IA, ME, MA, MN, MT, MS, NV, NH, NJ, NY, NM, OH, OK, OR, PA, RI, SC, TN, VT, WA, WI, and WY) proposed legislation to address marketing and direct-to-consumer advertising of pharmaceuticals. (http://www.acponline.org/advocacy/state_policy/reports/pharm_market.htm)
The end to unethical promotion of pharmaceuticals may be in sight.