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Merck & Co. appears to have played down or "misrepresented" the risk of dying for patients who took its once-popular pain medication Vioxx, according to a new study by researchers who reviewed court documents.

What's more, another study indicates Merck employees were the secret "ghost authors" of many trial results and academic papers used to promote the drug, which netted billions of dollars in sales.

Vioxx was pulled from the market in the fall of 2004 after research showed the medication increased the risk of heart attacks and strokes and that its use may have contributed to thousands of deaths.

The two new studies are being published in this week's edition of the Journal of the American Medical Association.

They are based on an analysis of court documents filed as part of subsequent lawsuits against the drug maker.

Last year, Merck agreed to pay $4.85-billion (U.S.) to settle most of the Vioxx claims.

The court documents provide a rare opportunity to see precisely how some blockbuster drugs are tested and marketed - and the results cast into doubt the integrity of medical science, says Catherine DeAngelis, editor of JAMA.

"It is just manipulation," she said, referring to the increasing use of industry-financed drug trials and ghost-written promotional articles to fuel pharmaceutical sales.

Merck issued a statement yesterday saying that "a full unbiased evaluation of the Merck papers shows that many of the conclusions put forward by the authors of the JAMA papers are incorrect."

However, Dr. DeAngelis pledged that all the material will be posted on the Internet "so anybody who questions the veracity of these two studies ... can go right to those sites and find everything they want."

One of the studies, which was written by researchers who served as paid consultants for those suing Merck, focused on two clinical trails in which Vioxx was tested on patients with Alzheimer's disease and dementia. The company was exploring the possibility that Vioxx, which was already on the market as a pain reliever, could help prevent the advance of Alzheimer's disease.

The researchers compared internal company documents with those submitted to regulators at the U.S. Food and Drug Administration as well as published studies.

They say the internal company documents suggest a threefold increase in deaths for patients taking Vioxx, compared with those getting a placebo. But this information was not passed on to the FDA in a clear and timely fashion, according to lead researcher Bruce Psaty of the University of Washington in Seattle.

"The counting methods that they submitted to the FDA appear to minimize the risk," said Dr. Psaty, referring to safety-update reports submitted to the FDA in 2001. For instance, the company did not initially report deaths of patients who had stopped taking the medication. "Adverse drug effects, however, may persist after drug discontinuation," Dr. Psaty and his co-author Richard Kronmal noted in their study.

"I have to say that the FDA was on the ball," said Dr. Psaty. "Despite these efforts to minimize the appearance of risk, the FDA, in their review of the submitted data, identified a mortality rate and asked Merck about it," Dr. Psaty said.

In response, Merck officials expressed the opinion that there was not a safety issue and said the drug was "generally" well tolerated. They characterize the difference in death rates between the Vioxx and the placebo group as "small numeric differences ... most consistent with chance fluctuations."

Dr. Psaty said Merck was "either unwilling or unable to discern a safety problem." And some of the mortality data wasn't submitted to the FDA until 2003.

Yesterday, Merck said it still stands by its original interpretation that there was no pattern suggesting the elevated deaths in the Vioxx group were connected to the drug. A statement issued by the company said "some of the deaths were caused by car accidents, poisoning, infections and other causes that are not related to Vioxx."

The second JAMA study, which was also conducted by researchers involved in the litigation against Merck, deals with the murky world of guest authorship and ghost writers of clinical trial and review papers.

Their analysis of the court documents reveals that Merck staff or hired hands designed, conducted and wrote up the results of a series of Vioxx studies and then looked for academics and physicians willing to put their names on the papers before they were submitted to journals for publication.

"When a few academic investigators ... are putting their names on the publication it [gives] the sense that it was objectively designed and there is an air of independence to the trial," said the study's lead author, Joseph Ross of Mount Sinai School of Medicine in New York.

He said the guest authors might have made some editing changes to a final manuscript for a study. But "nobody knows how fairly or truly objectively it was conducted. It questions the rigour of trial," Dr. Ross said.

Physicians were also asked to lend their names and credibility to ghost-written review articles that promoted the use of Vioxx.

Dr. Ross said the documents indicate guest authors were routinely paid honorariums by Merck, but this information was not always disclosed in the published study or review articles.

"It is almost like plagiarism." Dr. Ross said in an interview. "They are not being honest about their contributions. They are putting their names on papers they didn't actually design and conduct."

JAMA's Dr. DeAngelis uses a stronger word, calling it a form of "prostitution."

But Dr. Ross is not saying that every Vioxx study was ghostwritten.

One pivotal Vioxx study, known as the VIGOR trial, carried the name of a high-profile Canadian physician: Claire Bombardier, director of rheumatology at the University of Toronto.

"Let me dispel any doubt. Our paper was not 'ghostwritten,' " Dr. Bombardier said in an e-mail statement in response to the JAMA studies. She added that she, along with her co-authors, worked "diligently" on the paper.

"We were, and remain, proud of the important contribution our article made to medical science."

In an interview, Dr. DeAngelis called this "a sad day."

"I don't blame the pharmaceutical companies. I blame us because none of this would have happened if physicians and clinical scientists would just say no."

She noted that the court case has focused attention on Merck and Vioxx.

"But don't think for one minute that only Merck is guilty of this because they are not."