Merck Officials Explain Internal Documents Related To Safety Risks of Vioxx

Merck has begun "offering explanations" for internal documents that allegedly indicated the company was aware of the safety risks of the COX-2 inhibitor Vioxx years before the voluntary withdrawal of the medication in late September, the Wall Street Journal reports (Martinez, Wall Street Journal, 11/15).

In a previous article, the Journal described a 16-page internal instructional marketing document called "Dodge Ball Vioxx," which presented Merck sales representatives with sample physician questions about the safety concerns related to Vioxx and listed the correct responses as: "DODGE!" (American Health Line, 11/1).

On Friday, Kenneth Frazier, general counsel for Merck, said that the title of the document referred to a sales-training game that encourages sales representatives to answer physician questions with language approved by FDA. The game includes two teams that question each other on Vioxx, and if one team selects a card that reads "dodge," that team can pass on a question, he said.

Frazier also "provided context" for an internal e-mail sent by Merck research chief Edward Scolnick in which he referred to the safety risks of Vioxx (Wall Street Journal, 11/15). In the e-mail, Scolnick wrote that Vioxx research indicated cardiovascular events "are clearly there" and that the problem is "mechanism-based," or related to the effect that the medication has on the body (American Health Line, 11/1).

According to Frazier, Scolnick made the comments on the same day that the results of the clinical trial on which he based his conclusions became available to Merck, and "as such it represented the initial impressions on the data." Frazier added that Merck subsequently "unblinded" two placebo-controlled Vioxx trials on Alzheimer's patients and found no increased risk for cardiovascular events (Wall Street Journal, 11/15).

The New York Times and Washington Post on Saturday examined the removal of Curt Furberg, a professor at Wake Forest University, from an FDA advisory committee scheduled to review the safety of COX-2 inhibitors next year, after he publicly questioned the safety of Bextra, a COX-2 inhibitor manufactured by Pfizer.

Preliminary results of a University of Pennsylvania study presented last week at the American Heart Association annual conference in New Orleans indicated that Bextra doubles patient risk for heart attack and stroke. Furberg said FDA informed him that he would no longer participate on the committee after he said publicly that the results of the study indicate that Bextra appeared to have similar risks to Vioxx and that Pfizer attempted to conceal the information (California Healthline, 11/12).

According to Victoria Kao, a spokesperson for FDA, Furberg is "not barred forever from the panel" but was asked not to participate because of an "intellectual conflict of interest," the Times reports. Furberg, who said that he did not expect FDA to remove him from the committee, might present his data and opinions in a public comment period at the meeting (Kolata, New York Times, 11/13). "I think they're trying to control criticism at the committee meeting," Furberg said, adding, "The fact that I've commented on the issue should be irrelevant."

Sandra Kweder, deputy director of the FDA Office of New Drugs, said that the agency often removes advisory committee members who have financial or intellectual conflicts of interest. She added that FDA could reconsider the decision (Kaufman, Washington Post, 11/13).