Vioxx makers knew of drug's dangers three years before recall, says UW study

The maker of the controversial arthritis drug Vioxx knew of dangers associated with it for as many as three years before a massive nationwide recall, but withheld the information from federal officials and played down the number of deaths associated with the pain medication, according to an analysis published today by University of Washington professors.

The article, which appears today in the prominent Journal of the American Medical Association (JAMA), contends that Merck, which pulled Vioxx from the market in 2004, knew internally as early as 2001 that people at risk of Alzheimer's disease who were enrolled in two Vioxx clinical trials were dying at three times the rate of those taking a placebo.

The article, which examined previously secret Merck documents, contends the company switched calculations to minimize the number of deaths.

A Merck attorney, Jim Fitzpatrick of New York, countered today that the company disclosed all its clinical results thoroughly and that "we completely disagree" with allegations that Merck misrepresented its findings.

The article is one of two papers in this week's issue of JAMA investigating the clash of corporate interests and scientific integrity involving Vioxx, the subject of the most expensive drug recall in history.

In an accompanying editorial, JAMA's top editors call for "drastic actions" against corporate manipulation of clinical research and the practice of ghostwriting medical articles by unnamed authors on corporate payroll. It argues that researchers, regulators and even editors of medical journals such as JAMA are complicit. It singled out doctors who lend their names as authors on research papers for money for behavior "that is unprofessional and demeaning to the medical profession."

Both the article by UW professors and the companion paper on hidden authorship of articles on clinical trials rely on documents disclosed through some of the 27,000 Vioxx lawsuits against Merck. In November, the New Jersey company agreed to settle a majority of those suits for $4.85 billion without admitting guilt.

The co-author of the UW paper, Richard Kronmal, professor of statistics at UW, is a paid expert witness for Vioxx plaintiffs. The lead author is Bruce Psaty, UW professor of medicine.

Vioxx is a prescription arthritis drug and painkiller that was promoted as a gentler alternative to other drugs such as aspirin. Merck withdrew it in September 2004 after disclosing that a study found it doubled the risk of heart attacks and strokes.

But information was available well before 2004 that showed that Vioxx posed serious potential harm to subjects in clinical trials. As early as June 2000, unpublished data submitted to the Food and Drug Administration showed that taking Vioxx significantly raised the rate of heart attacks and strokes, as well as edema and hypertension, according to subsequent analysis by independent researchers.

Some of the same early evidence prompted pharmacists from Seattle's Group Health Cooperative to decide against adding Vioxx to its formulary. As a result, Group Health has never covered Vioxx for its members, said Jim Carlson, the co-op's director of pharmacy.

In the latest JAMA article, the UW researchers compared internal Merck memos about two Vioxx studies involving patients at risk of dementia against information the company submitted to the FDA and published later in two clinical papers.

In April 2001, a Merck statistician concluded that 34 people in the Vioxx groups had died, compared with 12 in the two placebo groups. But in its submissions to the FDA three months later, Merck used different methods to reduce the mortality risk, coming up with 29 deaths among Vioxx takers and 17 in the placebo groups.

Merck apparently did this in part by omitting some of the deaths that occurred after the subjects had stopped taking the drug, said Psaty.

"They were not being forthright," he said in an interview today. "They minimized the appearance of risk."

Kyung Song: 206-464-2423 or ksong@seattletimes.com