Merck Sales Associates Downplayed Safety Risks of Vioxx, House Committee Finds
Merck sales associates were given detailed instructions not to mention certain potential cardiovascular risks when promoting the company's COX-2 inhibitor Vioxx to doctors, according to an analysis of 20,000 pages of internal documents by congressional investigators for the House Committee on Government Reform delivered at a hearing Thursday, the Washington Post reports (Kaufman, Washington Post, 5/6).
Merck in September 2004 voluntarily withdrew Vioxx from the market, citing cardiovascular safety risks.
In March 2000, a Merck-funded study called VIGOR showed increased heart attack risks associated with Vioxx (Cohen, Newark Star-Ledger, 5/6). The study showed a fivefold increase in heart attacks among those who took Vioxx compared with those who took the painkiller naproxen. Merck said that the findings possibly were a result of a protective effect on the heart that naproxen provided, not an increased risk associated with Vioxx (Appleby, USA Today, 5/6).
According to company documents included in the congressional investigation, Merck in April 2000 developed a "Cardiovascular Card" for use in sales representatives' presentations to physicians. According to the committee, Merck's 3,000 sales representatives were instructed to refer doctors who raised questions about cardiovascular risks to the card, which indicated that Vioxx was eight to 11 times safer than other similar painkillers.
Information on the card was taken from several studies submitted to FDA and omitted any reference to the VIGOR study. An FDA advisory committee in 2001 voted that physicians should be informed of the VIGOR study findings.
According to the committee, Merck subsequently sent a memo to sales representative that stated, "Do not initiate discussions of the FDA arthritis committee ... or the results of the ... VIGOR study." Further, representatives were specifically directed to respond to doctors' questions about the study by saying, "I cannot discuss the study with you" (Newark Star-Ledger, 5/6). Additional cardiovascular risks of Vioxx were cited in an August 2001 study in the Journal of the American Medical Association (USA Today, 5/6).
After "extensive negotiations" with FDA, Merck in April 2002 agreed to a label change for Vioxx that included risks found in the VIGOR study. The label also included a statement that the significance of the findings was "unknown."
According to the committee, Merck told sales representatives "to emphasize the uncertainty of the VIGOR study to counter physicians' concerns," the Star-Ledger reports (Newark Star-Ledger, 5/6). Sales representatives were told to encourage doctors to submit any questions in writing to Merck's medical services department.
The company received 123,000 inquiries from physicians, according to Dennis Erb, Merck's vice president for regulatory issues (Alonso-Zaldivar, Los Angeles Times, 5/6).
According to the Post, Merck documents unearthed in the investigation indicate that sales representatives were given detailed instructions about how to approach physicians when selling Vioxx. "They were trained how to smile, speak and position themselves most effectively when talking with doctors," the Post reports (Washington Post, 5/6).
Representatives also were instructed how to use "verbal and nonverbal" cues to gain a physician's trust. Training materials indicated that representatives should shake a doctor's hand for no longer than three seconds.
Merck officials also informed representatives about "different personality types of doctors and recommended [sales] techniques for each type," the Star-Ledger reports (Newark Star-Ledger, 5/6). The training included motivational courses in which representatives were "taught not to take no for an answer." The courses compared milestones in sales of Merck drugs to points in the lives of Martin Luther King and Helen Keller.
Campaigns were titled "Project Offense" and "Project XXcelleration." In documents, doctors' concerns about risks were termed "obstacles." The company also used "sophisticated databases" to track the prescribing patterns of individual doctors and set targets for sales, according to the Los Angeles Times (Los Angeles Times, 5/6).
Representatives were given $2,000 bonuses for meeting sales goals (AP/New York Times, 5/6). According to the Los Angeles Times, Merck's marketing campaign was "astoundingly successful," with the "overwhelming majority" of prescriptions dispensed after concerns about heart risks had surfaced. Vioxx achieved sales of $2 billion annually "faster than any previous Merck drug," the Los Angeles Times reports (Los Angeles Times, 5/6).
The committee report states, "When concerns about Vioxx's safety arose, Merck appeared to use this highly trained force to present a misleading picture to physicians about the drug's cardiovascular risks." The report also said that Merck instructed its sales force to "emphasize outdated and misleading data that indicated Vioxx was safer than alternatives" (Newark Star-Ledger, 5/6).
Committee ranking member Henry Waxman (D-Calif.) at the hearing said, "This sales force is given extraordinary training so that it can capitalize on virtually every interaction with doctors. Yet when it comes to the one thing doctors most need to know about Vioxx -- its health risks -- Merck's answer seems to be disinformation and censorship" (Washington Post, 5/6). He asked, "Why did doctors write so many Vioxx prescriptions even as evidence of harm mounted?" He added that the company's "goal was sales, not education" (AP/New York Times, 5/6).
Rep. Gil Gutknecht (R-Minn.) called Merck's omission of potential risks in its presentations "confusing and, in some respects, embarrassing." He added that no one "wants to take responsibility for putting out information that an outside observer might call ... disingenuous."
FDA officials at the hearing testified that they were unaware of the details of Merck's marketing campaign, the Los Angeles Times reports (Los Angeles Times, 5/6).
Steven Galson, director of FDA's Center for Drug Evaluation and Research, said that Merck is legally obligated only to provide information that was approved in drug labeling (Newark Star-Ledger, 5/6). Galson said that that the promotional materials used by Merck sales representatives were "accurate based on the label, which was the standard we use" (Rovner, Congress Daily, 5/5).
However, Galson added that is "important that the company convey truthful information that is up to date." He also said that Merck appears not to have given doctors "the entire picture" (Newark Star-Ledger, 5/6). Galson acknowledged that the agency may have taken too long to remove Vioxx from the market (CQ HealthBeat, 5/6).
However, he said FDA is taking steps to improve awareness of drug risks (New York Times, 5/6). "The most important lesson ... is that the American public, practitioners and patients want to get clear and accurate information ... in their own health care decisions," Galson said.
Addressing Galson, Gutknecht said, "It seems to me there's a disconnect here. You're saying your policies are legal, but are they ethical? Isn't this the scandal?" (Washington Post, 5/6). Gutknecht also said, "Both the FDA and the pharmaceutical company sort of missed the mark" (Tansey, San Francisco Chronicle, 5/6).
Erb said at the hearing, "We believe Merck acted appropriately and responsibly to extensively study Vioxx after it was approved for marketing to gain more clinical information about the medicine." He added that the company "promptly disclosed the results of those studies to the FDA, physicians, the scientific community and the media" (Los Angeles Times, 5/6).
When asked by Committee Chair Tom Davis (R-Va.) whether a "wide awake" physician would have been aware of the drug's risks, Erb said, "That is correct" (AP/New York Times, 5/6). Erb added, "We believed wholeheartedly in the safety of Vioxx and that Vioxx was an important treatment option. My own father was a regular user of Vioxx" (Freking, AP/Las Vegas Sun, 5/6).
According to the San Francisco Chronicle, the committee's findings "could bolster moves by Congress to beef up the FDA's powers" (San Francisco Chronicle, 5/6).
Davis said, "As the committee conducted its investigation, it became apparent that the relationship between the Office of New Drugs and the Office of Drug Safety has its challenges." He said that the challenges include "a lack of communication between the offices, as well as communication up the chain of command" (CongressDaily, 5/5).
The committee report could also "prove a bonanza to plaintiffs in civil suits" against Merck alleging that Vioxx caused severe side effects or death, the Chronicle reports (San Francisco Chronicle, 5/6).
Erb said that Merck is in "preliminary discussions," with FDA to determine whether to apply for approval to resume marketing Vioxx in the United States.
An FDA advisory committee in February "narrowly" voted to recommend that Vioxx could be allowed back into the U.S. market under certain conditions, the AP/Times reports (AP/New York Times, 5/6).