Merck wrote drug studies for doctors

By Stephanie Saul
International Herald Tribune
Apr. 21, 2008

The drug maker Merck drafted dozens of research studies for a best-selling drug, then lined up prestigious doctors to put their names on the reports before publication, according to an article to be published Wednesday in a leading medical journal.

The article, based on documents unearthed in lawsuits over the pain drug Vioxx, provides a rare, detailed look in the industry practice of ghostwriting medical research studies that are then published in academic journals.

The article cited one draft of a Vioxx research study that was still in want of a big-name researcher, identifying the lead writer only as "External author?"

Vioxx was a best-selling drug before Merck took it off the market in 2004 over evidence linking it to heart attacks. Last fall, the company agreed to a $4.85 billion settlement to resolve tens of thousands of lawsuits filed by former Vioxx patients or their families.

The lead author of Wednesday's article, Dr. Joseph Ross of the Mount Sinai School of Medicine in New York, said a close look at the Merck documents raised broad questions about the validity of much of the drug industry's published research, because the ghostwriting practice appears to be widespread.

"It almost calls into question all legitimate research that's been conducted by the pharmaceutical industry with the academic physician," said Ross, whose article, written with colleagues, was published Wednesday in JAMA, The Journal of the American Medical Association, and posted Tuesday on the journal's Web site.

Merck acknowledged Tuesday that it sometimes hired outside medical writers to draft research reports before handing them over to the doctors whose names eventually appear on the publication. But the company disputed the article's conclusion that the authors do little of the actual research or analysis.

The final work is the product of the doctor and "accurately reflects his or her opinion," said a Merck lawyer, James Fitzpatrick.

And at least one of the doctors whose published research was questioned in Wednesday's article, Dr. Steven Ferris, a New York University psychiatry professor, said the notion that the article bearing his name was ghostwritten was "simply false." He said it was "egregious" that Ross and his colleagues had done no research besides mining the Merck documents and reading the published journal articles.

In an editorial, JAMA said the analysis showed that Merck had apparently manipulated dozens of publications to promote Vioxx.

"It is clear that at least some of the authors played little direct roles in the study or review, yet still allowed themselves to be named as authors," the editorial said.

The editorial called upon medical journal editors to require each author to report his or her specific contributions to articles. "Journal editors also bear some of the responsibility for enabling companies to manipulate publications," the editorial said.

JAMA itself published one of the Vioxx studies that was cited in Ross's article.

In that case, in 2002, a Merck scientist was listed as the lead author. But Dr. Catherine DeAngelis, JAMA's editor, said in a telephone interview Tuesday that, even so, it was dishonest because the authors did not fully disclose the role of a ghostwriter.

"I consider that being scammed," DeAngelis said. "But is that as serious as allowing someone to have a review article written by a for-profit company and solicited and paid for by a for-profit company and asking you to put your name on it after it was all done?"

Although the role of pharmaceutical companies in influencing medical journal articles has been questioned before, the Merck documents provided the most comprehensive look at the practice yet, according to one of the study's four authors, Dr. David Egilman, a clinical associate medical professor at Brown University.

In the Vioxx lawsuits, millions of Merck documents were supplied to plaintiffs. Those documents were available to Egilman and Ross because they had served as consultants to plaintiffs' lawyers in some of those suits.

Combing through the documents, Ross and his colleagues unearthed internal Merck e-mail messages and documents about 96 journal publications, which included review articles and reports of clinical studies. While the Ross team said it was not necessarily raising questions about all 96 articles, it said that in many cases there was scant evidence that the recruited authors made substantive contributions.

One paper involved a study of Vioxx as a possible deterrent to Alzheimer's progression.

The draft of the paper, dated August 2003, identified the lead writer as "External author?" But when it was published in 2005 in the journal Neuropsychopharmacology, the lead author was listed as Dr. Leon Thal, a well-known Alzheimer's researcher at the University of California, San Diego. Thal was killed in an airplane crash last year.

The second author listed on the published Alzheimer's paper, whose name had not been on the draft, was Ferris, the New York University professor. Ferris, reached by telephone Tuesday, said he had played an active role in the research and he was substantially involved in helping shape the final draft.

"It's simply false that we didn't contribute to the final publication," Ferris said.

A third author, also not named on the initial draft, was Dr. Louis Kirby, currently the medical director for the company Provista Life Sciences. In an e-mail message on Tuesday, Kirby said that as a clinical investigator for the study he had enrolled more patients, 109, than any of the other researchers. He also said he made revisions to the final document.

"The fact that the draft was written by a Merck employee for later discussion by all the authors does not in and of itself constitute ghostwriting," Kirby's e-mail message said.

The current editor of the journal Neuropsychopharmacology, Dr. James Meador-Woodruff, the chairman of psychiatry at the University of Alabama, Birmingham, said he was not the editor in 2005 but planned to investigate the accusations. "Currently, we have in place prohibitions against this," Meador-Woodruff said.