Internal E-mails Indicate Merck Was Aware of Vioxx Risks
Internal e-mails, marketing documents and interviews with outside scientists who questioned the safety of the arthritis medication Vioxx -- a COX-2 inhibitor that Merck in September decided to withdraw from the market -- indicate that the company "fought forcefully for years to keep safety concerns from destroying the drug's commercial prospects," the Wall Street Journal reports.
Several internal e-mails examined by the Journal indicate that Merck officials discussed the increased cardiovascular-related risks related to Vioxx and proposed to design studies that would "minimize the unflattering comparison" with less-expensive, older pain medications, the Journal reports.
In 1997, Merck official Briggs Morrison wrote that to conduct a study that would not indicate a significantly increased risk of blood clots among patients who took Vioxx compared with those who took aspirin -- a result that he said would "kill the drug" -- participants who took Vioxx also would have to take aspirin. However, according to a 1996 memo, such a study would limit evidence that Vioxx is gentler on stomachs than older pain medications. In response, Alise Reicin, currently a Merck vice president for clinical research, proposed a study that excluded individuals at high risk for cardiovascular problems to ensure differences among participants who took Vioxx and those who took older pain medications "would not be evident." The 1999 study, called Vigor for Vioxx Gastrointestinal Outcomes Research, involved 8,000 patients who took either Vioxx or naproxen; none of the participants took aspirin. Although the study excluded individuals at high risk for cardiovascular problems, the results indicated that participants who took Vioxx had four times the risk for heart attack as those who took naproxen.
In 2000, Edward Scolnick, research chief for Merck, wrote to colleagues that the cardiovascular events "are clearly there" and that the problem is "mechanism-based," or related to the effect that Vioxx has on the body. He added that he would seek additional data before he presented the study results to the public to ensure "it is clear to the world that this" was an effect of all COX-2 inhibitors, not only Vioxx.
In response to the Scolnick e-mail, Merck "offered no hint ... that there was a 'mechanism-based' problem with Vioxx or a 'hazard' that went beyond Vioxx's failure to offer the protective benefits of other painkillers," the Journal reports. One month after the e-mail, Merck officials issued a news release that said the company had confirmed the "favorable cardiovascular safety profile" of Vioxx, adding that the Vigor study found "NO DIFFERENCE in the incidence of cardiovascular events" between Vioxx and placeboes or Vioxx and older pain medications.
However, according to internal marketing documents, Merck sales representatives should tell physicians who raised concerns about whether Vioxx could increase the risk of cardiovascular problems for patients that the medication "would not be expected to demonstrate reductions" in heart attacks and was "not a substitute for aspirin." In a 16-page instructional document called "Dodge Ball Vioxx," Merck sales representatives are presented with sample physician questions about the safety concerns related to Vioxx, and the correct responses are listed as: "DODGE!" Ted Mayer, an attorney for Merck, declined to discuss the marketing documents but said that the company trained sales representatives to discuss Vioxx in a manner "consistent with FDA-approved labeling" and were "not trained to avoid physicians' questions."
Merck also "went on the offensive" against outside scientists who questioned the safety of Vioxx, according to the Journal. For example, Dr. Gurkirpal Singh, a COX-2 specialist at Stanford University who delivered presentations sponsored by Merck and other pharmaceutical companies, "pressed Merck repeatedly" for data on the cardiovascular risks of Vioxx, the Journal reports. After Merck refused, Singh added a slide to his presentation that "showed a man -- representing the missing data -- hiding under a blanket." In response, Merck canceled several of his presentations and said that they were "irresponsibly anti-Merck and specifically anti-Vioxx."
In addition, when Dr. Joan-Ramon Laporte of the Catalan Institute of Pharmacology in Spain edited a publication that included safety concerns about Vioxx, Merck officials sent him a "rectification" for publication. After he refused, Merck filed a lawsuit against him and the institute. A judge ruled in favor of LaPorte in January. However, when organizers for an annual Spanish family physician meeting in March denied a request from Merck to remove Laporte from the list of scheduled speakers, Merck withdrew about $140,000 in funds for the meeting. In other cases, Merck has asked outside scientists to "delete or tone down" negative statements about Vioxx and has removed the name of an employee from a Vioxx study with negative results (Wilde Mathews/Martinez, Wall Street Journal, 11/1).