Monday, December 15, 2008

The Haunting of Hormone Replacement Therapy

US Senator Charles Grassley (R-Iowa) is digging into what appears to be another ghost-writing case. As reported by the New York Times,

Wyeth, the pharmaceutical company, paid ghostwriters to produce medical journal articles favorable to its hormone replacement therapy Prempro, according to Congressional letters seeking more information about the company’s involvement in medical ghostwriting.

Mr. Grassley’s staff on the Senate Finance Committee 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.

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 issue of ghostwriting for medical journals has been raised in the past, involving various companies and drugs, including the Merck painkiller Vioxx, which was withdrawn in 2004 after it was linked to heart problems, and Wyeth’s diet pills, Redux and Pondimin, withdrawn in 1997 after being linked to heart and lung problems.

But the documents Mr. Grassley released Friday provide a detailed look at the practice — from the conception of ideas for journal articles through the distribution of reprints.

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.

A companion article tracked the process of creating a single article. It included the strategy meeting in which the article was conceived by Wyeth staff:

Agenda item II for a Sept. 19, 1997, meeting by company staff members involved the “SHBG Outline.” It is an apparent reference to the working outline of an academic article about the protein SHBG — sex hormone-binding globulin — in breast cancer. The planned steps included initiating contact with Dr. Lila E. Nachtigall, of the New York University Medical School, who would be asked to serve as the article’s author.

Then the ghost-writers were chosen:

A fax from Karen Mittleman, a DesignWrite writer, to Ann Contijoch, a professional medical writer with a Ph.D. in animal science, about developing and improving an outline and reference list for the article. (The document appears to be dated 2005, but that was the date it was obtained in a lawsuit; it was actually dated 1998.)

In the Times interview, Dr. Nachtigall said that Ms. Mittleman had helped her prepare slides for talks but that she had never heard of Ms. Contijoch.

Reached by telephone Friday, Ms. Contijoch said she did not remember whether she had drafted the outline or the manuscript but that she had provided 'editorial assistance,' like copy editing, while Dr. Nachtigall 'drove the content.'

Then the article outline was revised:

DesignWrite prepared a revised outline. Some of the outline’s language appeared verbatim in the final journal article.

Dr. Nachtigall told The Times that the outline might have been based on her previous work and that she must have prepared the references list herself.

Then the draft was sent to the supposed academic first author:

A subsequent letter, written sometime in 1998, to Dr. Nachtigall from Ms. Mittleman of DesignWrite told the doctor that the draft manuscript of the article was on its way to her.

The article finally appeared:

When the article was published in 1999 in the journal Primary Care Update for OB/GYNs, it listed Dr. Nachtigall as the author, but did not mention Wyeth or DesignWrite. The end of the article acknowledges 'editorial assistance' from Ms. Contijoch but does not further identify her.

In the Times interview, Dr. Nachtigall said, 'Ann Contijoch – I’ve never heard of that person.'

The article is Nachtigall LE. Sex hormone-binding globulin and breast cancer risk. Primary Care Update Ob/Gyns 1999; 6: 39-45.

By the way, at the end of the first NY Times article, Dr Nachtigall responded to Senator Grassley's inquiries thus:

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.

So as long as people are robbing banks, the police should not care about petty theft? In fact, we should care about this sort of ghost-writing, since it is a difficult to detect deception which disguises marketing as scholarship. This latest case adds to the evidence that ghost-writing is a prevalent problem.

As we and others have said before, ghost-writing is dangerous to health, as it deludes physicians and patients into thinking health care products are more beneficial and less risky than they really are. Ghost-writing also undermines science by shifting the agenda away from interesting and important questions to questions whose answers may mainly benefit vested interests. Finally, on a personal note, ghost-writing demoralizes honest academics who must run their own studies, write their own papers, and manage the logistics of paper submission in competition with fake authors backed by corporate money and corporate staff. So, Dr Nachtigall deserves no break.

1 comment:

Anonymous said...

On a related note Robert Lee Holt in the Dec. 12, 2008 WSJ article What You Don't Know About a Drug Can Hurt You subtitled: Untold Numbers of Clinical Trial Results Go Unpublished; Those That Are Made Public Can't Always Be Believed highlights how negative information is simply withheld from the public and concerned doctors.

Two important quotes from this lengthy article are:

"In September, medical informatics expert Ida Sim at UCSF and her colleagues reviewed 900 FDA filings involving 90 new drugs and reported that more than half of the clinical trials were still unpublished 5 years after the drugs had been approved."


"Moreover, when clinical data is published in one of 5,200 peer-reviewed biomedical journals, the information on health risk and benefits may be biased by spin and selective reporting, medical analysts said."

Ultimately the real issue becomes, not only is the published information of questionable value, but not all of the information available is made public. How can a doctor, let alone a patient, make an informed decision about a course of medical treatment when economic issues are the only driver in the information available to both of them.

My personal belief is that pharma's corporate culture of half-truths and spin so permeates much of medical culture that doctors and patients are being forced to question all available medical information. No longer can an endorsement by a medical institution, or medical leadership, be accepted due to not only undisclosed conflicts, but an unwillingness to disclose conflicts, even as part of a larger corporate directive.

Steve Lucas