Wyeth paid ghostwriters to produce medical journal articles favorable to its Prempro hormone replacement therapy, according to Congressional letters seeking more info about the drugmaker’s involvement in medical ghostwriting, The New York Times reports, adding that at least one article was published even after a federal study found the drug raised the risk of breast cancer.

The letters, sent electronically today by Chuck Grassley, the ranking Republican on the Senate Finance Committee, asks Wyeth and DesignWrite, a medical writing firm, to disclose payments related to the preparation of journal articles and the activities of doctors who were recruited to put their names on them for publication, the Times writes.

“Any attempt to manipulate the scientific literature, that can in turn mislead doctors to prescribe drugs that may not work and/or cause harm to their patients, is very troubling,” Grassley wrote Wyeth ceo Bernard Poussot. Phone calls and e-mail messages to Wyeth and DesignWrite were not immediately returned to the Times.

Grassley’s staff released dozens of pages of internal corporate documents gathered from lawsuits showing the central, previously undisclosed role of Wyeth and DesignWrite in creating articles promoting hormone therapy for menopausal women as far back as 1997 (look here for a brief rundown).

One article was published as an ‘Editors’ Choice’ feature in May 2003 in The American Journal of Obstetrics and Gynecology, more than a year after a federal study called the Women’s Health Initiative linked Prempro, a combination of estrogen and progestin, to breast cancer, the paper writes. The May 2003 article said there was “no definitive evidence” that progestins cause breast cancer and added that hormone users had a better chance of surviving cancer, the Times continues.

At the peak of hormone therapy, in 2001, more than 126 million prescriptions for such drugs were written for women in the US, and sales that year, primarily by Wyeth, were $3 billion. But after the federal finding, sales of the hormone drugs plummeted.

The documents show company executives came up with ideas for medical journal articles, titled them, drafted outlines, paid writers to draft the manuscripts, recruited academic authors and identified publications to run the articles — all without disclosing the companies’ roles to journal editors or readers, the Times writes.

The articles all involve reviews of clinical studies and other research. While such reviews are common in medical publishing, Grassley contends the Wyeth-commissioned articles involved expert authors whose names appear on the articles and became involved only after outlines or drafts of the articles were already written.

When accusations of ghostwriting have cropped up in patient lawsuits over its hormone drugs, Wyeth execs to date have insisted their publication practices were legit and the listed authors played significant roles in journal articles.

But the documents released Friday include a “publication plan tracking report” by Wyeth showing 10 articles in which manuscripts were completed by the company before they were sent to the putative author for review. Any revisions were subject to final approval from the company, according to the tracking report.

Such activities would seem to run afoul of medical journal guidelines. The International Committee of Medical Journal Editors says authorship means “substantive intellectual contributions” including conception or analysis of the subject and drafting or critical revision of the document, the Times notes. The World Association of Medical Editors says ghost authorship - which it defines as a substantial contribution not mentioned in the manuscript - is “dishonest and unacceptable.”

Congressional investigators were given the documents about a month ago by James Szaller, a personal injury lawyer in Cleveland who hasr collected the documents from court filings and made reference to some in an article he wrote last year for a law magazine, Trial. “For the last three years, I’ve looked at ghostwriting at Wyeth,” Szaller tells the Times. “There is a mammoth amount of material. The problem is that almost all of it is still under seal.”

In Friday’s letter, Grassley asked Wyeth to list all scientific reports prepared for the company by DesignWrite since January 1, 1995, to describe the named authors’ “extent of involvement” and to disclose fees paid to DesignWrite, authors and others. He also requested “all internal and external correspondence, communications and meeting minutes regarding each of the DesignWrite-prepared studies,” according to the Times.

The letter to DesignWrite requested all manuscripts prepared for Wyeth since 1995, along with information on related payments and a description of the author’s involvement, the paper reports.

The May 2003 article supporting Prempro was signed by John Eden, an associate professor at the University of New South Wales and director of the Sydney Menopause Center in Australia. Wyeth execs suggested Eden write such a paper in 2000, according to the documents, and had the outline and draft manuscript written for him. The Archives of Internal Medicine rejected the paper before it was published in The American Journal of Obstetrics and Gynecology - with no mention of Wyeth or DesignWrite connections, according to the Times. Eden did not respond to the Times.

In another case, documents show, Lila Nachtigall, a New York University professor and director of its Women’s Wellness Center, was recruited by Wyeth as author of a 1999 journal article extolling hormone treatment after the manuscript had already been drafted, according to the Times.

Nachtigall tells the paper she wrote all of the approximately 1,000 articles and three books she has had published. Asked about the Wyeth documents, she says: “If they came up with the idea or gave me an outline or something, I don’t remember that at all.” Nachtigall, who is still practicing at age 75, adds: “It kind of makes me laugh that with what goes on in the Senate, the senator’s worried that something’s ghostwritten. I mean, give me a break.”

Two months before the negative findings of the federal study were released, a May 2002 memo to DesignWrite employees said that Michael Dey, who was president of Wyeth’s Women’s Healthcare Business unit, asked a committee to increase the number of positive journal articles related to another of its hormone replacement drugs, Premarin. “Mike would like us to publish at least 1 study per month,” the memo said, according to the Times.

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UPDATE: “We now insert the following statement from a Wyeth spokesman: “Wyeth will provide a full response to Senator Grassley’s letter, which we just received. It is important to note, however, that this inquiry appears to represent an effort by plaintiffs’ product liability attorneys to recycle arguments that have been rejected by judges and juries alike. For example, NJ judge Jamie Happas, who is overseeing Hormone Therapy litigation in that state, said in an opinion commenting on some of the same articles addressed by Senator Grassley: “There is no dispute that the articles were subject to a rigorous peer review process and were factually and medically sound.” Similarly, Judge William R. Wilson, U.S.D.J. overseeing the federal Hormone Therapy litigation, concluded that there was no evidence that Wyeth supported articles that it knew were false or misrepresented the science. He noted that plaintiff’s own expert witness conceded that she had engaged in the practice herself. The authors of the articles in question, none of whom were paid, exercised substantive editorial control over the content of the articles and had the final say, in all respects, over the content.”