The Indictment of Pharma Industry Marketing Practices

Pharmacology Watch

A team from UCSF recently reviewed company documents that were entered into the public record as a result of litigation over the promotion of gabapentin (Neurontin) between 1994 and 1998. The result, a rather scathing indictment of the pharmaceutical industry's marketing practices, is published in the August 15 Annals of Internal Medicine.

The authors had access to thousands of pages of inside company documents from Pfizer, Parke-Davis, and Warner-Lambert regarding the marketing of gabapentin during a time that the drug was a blockbuster, with sales in the hundreds of millions of dollars.

The primary focus of the litigation was the promotion of off-label indications of gabapentin by Parke-Davis. The paper highlights the company's marketing strategy, which included identifying groups of physicians for targeted marketing. Local champion physicians were identified and trained as "peer-to-peer selling" program leaders. The company also identified physician thought leaders in academic medicine who were given large honoraria, research grants, and educational grants to promote the drug. Resident physicians were also targeted, and large sums of money were given to residency programs. Medical education was one of the cornerstones of the marketing plan.

Physician lectures, teleconferences, and other meetings were set up discuss treatment of epilepsy, but also to discuss off-label use of the drug. Parke-Davis employees frequently surreptitiously listened in on these meetings electronically, in part to gauge the effectiveness of the presentation. Physician moderators were paid well for their participation.

Parke-Davis also developed speaker's bureaus and created academic neurologic lecture series for the neurology community. Department chairs and clinical training program directors were frequently on the speakers lists of these programs. The company also gave unrestricted grants through third-party medical education companies which allowed speakers to legally discuss off label use of gabapentin and to grant CME credits.

A Parke-Davis memo describes these activities as a "growth opportunity" for off-label use of the drug. Physician advisory boards were also well paid to attend meetings where promotional activities were discussed. Research was also directed by the company, and there are indications that studies that gave favorable outcomes were more likely to be published than studies that were not favorable to the drug.

The company also promoted review articles and letters to the editor of journals regarding gabapentin for as much as the $18,000 per article. The authors point out that activities "traditionally considered independent of promotional intent" such as CME and research were cornerstones of marketing efforts, and when run through a third party, were legal marketing forums for off-label uses of the drug. The authors call for new strategies to "ensure a clear separation between scientific and commercial activity" (Ann Int Med. 2006;145:284-293). This paper is a must read for anyone involved in formulary management, cost effective prescribing processes, or medical education.

TNF Blockers: Should You Be Concerned?

The use of TNF blockers for treatment of rheumatoid arthritis has always been clouded by the potential risk of lymphoma or solid cancers. A new study suggests that the concern may be unfounded.

Researchers from Harvard and University of British Columbia performed a cohort study pooling data from 1152 RA patients who received a biologic DMARD (the TNF blockers etanercept, infliximab, adalimumab, or anakinra) and 7306 patients who received methotrexate. Both groups of patients had elevated risks of cancer compared to the general population, but the overall hazard ratio for hematologic and solid tumors for patients receiving a biologic DMARDs vs methotrexate was 0.98 (1.11 lymphoproliferative cancers 1.37 for hematologic malignancies, and 0.91 for solid tumors).

The authors conclude that biologic agents are unlikely to have a substantial increase in the risk of hematologic malignancies and solid tumors as compared with methotrexate users (Arthritis Rheum. 2006;54:2757-2764).

FDA Actions

The FDA has approved over-the-counter access for Plan B, the so-called morning-after pill. Over-the-counter sales of Plan B have been a contentious issue on Capitol Hill throughout the Bush presidency, and it took a change in leadership in the FDA to bring about the change in position. Plan B will be available for women ages 18 and older without a prescription; however, a prescription is still required for women ages 17 and younger. Plan B is marketed by Duramed, a subsidiary of Barr Pharmaceuticals.

Several SSRI antidepressants have made the switch to generic, including fluoxetine, paroxetine, citalopram, and sertraline. Now the first generic serotonin/norepinephrine reuptake inhibitor has been approved. Venlafaxine (marketed as Effexor) was approved for generic switch in August in 25 mg, 37.5 mg, 50 mg, 75 mg, and 100 mg strengths. TEVA pharmaceuticals have exclusivity on the generic for 180 days.

The FDA has approved the use of clopidogrel (Plavix -Bristol-Myers Squibb) in patients with ST segment elevation myocardial infarction (STEMI) who are not going to have coronary artery interventions. The new indication for the drug was based on the findings of 2 studies (COMMIT and CLARITY), which showed improved outcomes with use of the drug in STEMI patients, including those who had initial thrombolytic therapy.

In related news, a somewhat bizarre patent battle over clopidogrel is raging between Bristol-Myers Squibb and Canadian generic maker Apotex. The Canadian company challenged the patent, and introduced generic clopidogrel to the American market on August 8. On August 31, a federal judge in New York issued a restraining order to block distribution of the generic version of the drug; however, she did not require a recall of the generic pills already on the market. Bristol-Myers, which derives 30% of its yearly profit from sales of Plavix, is unsure how much generic product was distributed in 4 weeks; most estimates are approximately 3 months supply. Meanwhile, the patent trial is scheduled to begin in January.

The FDA's Center for Drug Evaluation and Research has issued a warning regarding concomitant use of ibuprofen and aspirin for patients who are taking aspirin for cardioprotection. Functional studies have shown that ibuprofen blocks the effect of aspirin on platelets if the 2 drugs are taken at the same time. Both drugs inhibit cyclooxygenase on platelets. Aspirin's effect is irreversible for the life of the platelet, whereas ibuprofen and other NSAIDs cause reversible inhibition. If ibuprofen is taken before or concomitantly with aspirin, the receptor site is occupied and aspirin is unable to exert its effect. However, if aspirin is taken 30 minutes before ibuprofen or 8 hours after, there is no competitive inhibition. The FDA is recommending that physicians be aware of the timing of ibuprofen and, perhaps, other NSAIDs when used with aspirin, and specifically recommend that aspirin be given 30 minutes prior to ibuprofen or 8 hours later. Recommendations regarding enteric-coated aspirin are unavailable at this time.

This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5416. E-mail: