Following a Wyeth article

In the late 1990s and early 2000s, Wyeth needed to market its hormone therapies to postmenopausal women. It was facing competition from new drugs and increasing evidence that hormone therapies did more harm than good. Wyeth turned to companies like DesignWrite and OCC to create suites of articles and conference presentations that would expand the market and reassure women and their doctors. Because of a lawsuit, many documents from those interactions are now available for public scrutiny. Over six years, DesignWrite produced for Wyeth “over 50 peer-reviewed publications, more than 50 scientific abstracts and posters, journal supplements, internal white papers, slide kits, and symposia….” (http://dida.library.ucsf.edu/tid/iwb37b10)

Let’s follow an article from Wyeth’s work on its new hormone therapy Totelle, containing estradiol and trimegestone.

On August 16, 2002, Jean Wright, working for Parthenon Publishing, of Lancaster, UK, wrote to a group of Wyeth employees:

Please find attached the first draft of PC(2): A 2year comparison of the effects of continuous combined regimens of 1 mg 17bestradiol and trimegestone with regimens containing estradiol and norethisterone acetate upon endometrial bleeding and safety in postmenopausal women, for initial review. (http://dida.library.ucsf.edu/pdf/unc37b10)

Under the title of the draft is “Author: to be determined” (http://dida.library.ucsf.edu/pdf/uoc37b10).

A March 4, 2003 tracking report shows the following:

Paper PC(2) FAST TRACK
A comparison of the effects of continuous combined regimens of 1 mg 17p-estradiol and trimegestone with
regimens containing 1 or 2 mg 17p-estradiol and norethisterone acetate upon the bleeding profile and endometrial safety in postmenopausal women

First draft submitted for initial review August 11
Comments received from Daniele December 7
Revised draft submitted January 3
Comments received from Sophie February 5
Revised draft submitted to Gary February 28
Comments received from Richie, February 28
(http://dida.library.ucsf.edu/pdf/luc37b10)

At that point, this high-priority manuscript had been twice been revised by Parthenon in response to comments by Wyeth employees Daniele and Sophie, and had yet to be revised in light of Richie’s comments. The third draft was sent to the publication team on March 12, and the fourth on July 2 (
http://dida.library.ucsf.edu/pdf/dob37b10). It had not yet been seen by an outside author – though by April 2 authors finally appeared on the tracking report, and Wyeth’s Daniele (Spielmann) was the third author on the manuscript. A note on the author list said “Need to contact” (http://dida.library.ucsf.edu/pdf/chb37b10). By June 6, 2003, the manuscript had clear authors: “Bouchard P, Addo S, Spielmann D, and the Trimegestone 301 Study Group”. The last of these was the very long list of physicians who had provided patients for the Wyeth trial.

But that was not quite the end of the line for the manuscript. An October 27 tracking report lists:

(7-10-03) Being updated by Parthenon, then out to external authors for final review.
(7-17-03) Must be submitted by July 31st.
(8-18-03) This got held up during Wyeth sign-off process and has not been submitted.
(8-29-03) Sign-off almost completed.

(9-22-03) In final stages of sign-off at Wyeth.
(
http://dida.library.ucsf.edu/pdf/ylb37b10)

But confusingly, the author list had changed. It had become “Bouchard P, De Cicco-Nardone F, Spielmann D, Garcea N, and the Trimegest one 301 Study Group”. What has happened? An email by Daniele Spielmann explained: “The 2 italian authors agree with the paper and replace ADDO woho [sic] went to our competitors” (http://dida.library.ucsf.edu/pdf/dsc37b10). In a separate email Jean Wright of Parthenon wrote: “Please note that S. Addo has been deleted from the author list for PC(2). Daniele was doubtful whether she should be included because she now has connections with Organon” (Organon being another drug company) (http://dida.library.ucsf.edu/pdf/dpb37b10).

Although a 2004 tracking report listed the manuscript as accepted in the journal
Menopause (http://dida.library.ucsf.edu/pdf/gyc37b10), for some reason it actually appeared in the journal Gynecological Endocrinology, in 2005. Gynecological Endocrinology was a journal published by Parthenon (now part of the company informa).

What can we take from this short but tortuous story? Manuscripts like this run a gauntlet of reviews by planners and drug company scientists. They have already been vetted and revised many times before their authors are chosen. Chances are, as appears in this case, authors have little to add other than their names and endorsements. By the time that they are submitted to medical journals, ghost managed manuscripts have already gone through more careful scrutiny – though with somewhat different goals – than the journals will give them.

Authors are interchangeable. The authors were all “TBD” or “To be determined” until the publication team thought that the manuscript was almost ready to be sent out to a journal. Only then were the authors added, and perhaps without a lot of consultation. When Dr. Addo established ties to Organon, Wyeth no longer wanted to work with her, and simply replaced her with two other authors.