New Ways to Investigate Untold Health Stories (Antidote)
By William Heisel
It’s not as seductive as a candlelit bedroom.
But a dinner with medical colleagues after a board meeting can exert a powerful a pull on talented scientists flirting with the drug industry. 
Rarely one-on-ones, these dinners are usually threesomes:
1. The seducer: a representative for a medical communications company that has been hired by a drug company to help market a particular product or disease in need of new cures being cooked up by the company.
2. The object of seduction: a researcher with known expertise in the company’s target area.
3. The wing man: A veteran researcher who already has worked with a ghostwriter and can lend the communications company credibility.
In 2000, Dr. John Eden had dinner with a representative from DesignWrite, Mark Barbee, and a fellow researcher, Dr. David F. Archer. The meeting was Eden’s first brush with the company that would end up handing him an article it had written with funding from drug giant Wyeth, an article that downplayed the side effects of hormone replacement therapy (HRT). It was published in the wake of a groundbreaking study that was halted after showing a strong correlation between HRT and breast cancer.
Without Archer at that dinner, the DesignWrite rep would have been just another corporate suit. With Archer, suddenly Barbee was part of The Science Club. He wrote Eden in July 2000:
I very much enjoyed meeting you recently in New York at the Perspectives in ERT/HRT: Advisory Board Meeting. Just in case you are having trouble placing me, we had dinner the first night with Dr. Archer. I am one of the marketing managers for the Premarin Family of Products. Your comments were invaluable to us as we move our business forward.
Eden and Archer had been asked by Wyeth to present their thoughts on HRT, and now Barbee was hoping Eden would take the next step and allow his name to be used on an article that he did not write.
Considering the current environment, I would like to know if you would have an interest in working with a writer from DesignWrite to enrich the literature in the U.S. with a review article. DesignWrite works with Premarin Marketing Team on our publication planning. They have knowledgeable and gifted writers that would work with you on the article. Wyeth cannot pay you for this endeavor, but we can offer the assistance of a writer. Your insights into breast cancer and its relationship to HRT would be insightful information to U.S. healthcare providers.
Eden eventually said yes, a decision he now regrets.
Archer was already a veteran. In 1999, DesignWrite hooked him to “author” a review paper titled “Progestins in HRT.” Soon, he was putting his name to multiple papers and serving as an editorial consultant for the company.
Archer and a co-researcher, James H. Pickar, signed their names to a paper that had been written with help from DesignWrite/Wyeth: “Hormone replacement therapy: effect of progestin dose and time since menopause on endometrial bleeding.” They submitted the paper to the journal Obstetrics & Gynecology. The journal published the paper in December 2000.
A continuous combined regimen of CEE plus 5.0 mg MPA may be more suitable for women closer to the onset of menopause or for women starting therapy who are unwilling to tolerate irregular bleeding. The improved bleeding profile with CEE and 5.0 mg/day MPA is likely to enhance compliance with hormone replacement therapy.
This is a perfect advertisement for a version of Wyeth’s signature HRT combo: Premarin (CEE) and Prempro or Premphase (MPA). The author affiliations listed on the paper were the Jones Institute for Reproductive Medicine at Eastern Virginia Medical Center in Norfolk, where Archer continues to work (and pump out research articles) to this day and Wyeth, where Pickar works. The article also disclosed that “Author Archer has served as a paid consultant and has received grants from Wyeth-Ayerst Pharmaceuticals.”
Archer should be commended for disclosing his consulting work. But mentioning a drug company is not the same as full disclosure. Nowhere is there a mention that the article had been conceived, researched and written directly by DesignWrite and Wyeth. Here, again, Archer is lending seemingly independent credibility to DesignWrite and Wyeth. Without his name on the paper, the article would appear to be what it actually is, a product created by Wyeth to sell Wyeth products.
By providing this arms-length veneer of independence and objectivity, Archer helped DesignWrite open the door to journal after journal for Wyeth. He is part of a group of researchers working with DesignWrite that have allowed Wyeth to rack up a long list of “Premarin Family” review papers published from 1998 through 2001.
The journals are just as much to blame. Why do journal editors agree to publish papers purporting to review the scientific literature from an independent vantage point but signed by authors with obvious and, sometimes, stated conflicts?
Antidote called Archer to ask about the articles. He initially agreed to talk but cancelled at the last minute and later sent an email saying:
Please note, I was not “hired” by DesignWrite nor was I paid for these articles. My service as a consultant or status as a grant recipient was disclosed and noted in the various articles you reference. Similarly, Menopausal Medicine, published by the American Society of Reproductive Medicine, noted in its banner that the newsletter received support from Wyeth-Ayerst Laboratories.
I chose to participate in the development of these articles, in some cases, because I believed the information was worthy of being shared with other physicians and, in other cases, because participation provided me the opportunity to review results to which I might not otherwise have had access.
By “banner,” he means the list of editorial staff that runs on the inside of the newsletter. The company’s logo appeared, about the size of a paper clip, at the bottom of the page.
Antidote asked Dr. Anthony Scialli, an adjunct professor in obstetrics and gynecology at Georgetown University Medical Center and a senior scientist for the Tetra Tech Sciences consulting firm, what he thought about Archer’s level of disclosure. Here’s what he had to say:
Authors should be listed as authors, so the nonlisting of a professional writer as an author would not be appropriate. There are frequently times when an author has not actually written a paper. Consider, for example, five scientists who publish a paper together. Often one of them will have written the first draft and the others will make changes and suggestions until a consensus document emerges. In these cases, the non-writing authors will have contributed ideas or will have designed the study or provided some tangible contribution.
Instead of Archer being the lead author and the DesignWrite writers being left out entirely, Scialli said, it should be the reverse:
If a professional writer is paid by a company to write a piece and a non-author doctor is asked to approve it, the appropriate outcome would be for the professional writer to be listed as the author and for the non-author doctor to be thanked in an acknowledgement for having reviewed the paper. If the non-author doctor makes substantial enough changes to the paper, he or she might be listed as a coauthor. In either case, the funding for the paper should be disclosed.
Archer declined to answer any follow-up questions. Antidote will post more about Archer’s adventures on Monday.
Dr. Archer’s Ghost Part 2: This gun for hire has only one bullet
In June 2002, Dr. David F. Archer had a paper published under his name that reassured women everywhere that they could take antibiotics and birth control pills at the same time and not worry about pregnancy. The article was music to the ears of executives at Wyeth, the drug company giant.
Archer had championed two pharmaceutical categories important to Wyeth: birth control pills and antibiotics. Some gynecologists and family practice doctors had been reluctant to prescribe both, mainly because women had reported becoming pregnant while taking them at the same time. No worries, said the paper. Titled: “Oral contraceptive efficacy and antibiotic interaction: a myth debunked,” it explained:
Available scientific and pharmacokinetic data do not support the hypothesis that antibiotics (with the exception of rifampin) lower the contraceptive efficacy of oral contraceptives.
Archer’s author affiliations appeared purely academic: “Clinical Research Center, Jones Institute for Reproductive Medicine, Eastern Virginia Medical School.” And his conflict of interest disclosure had the appearance of complete transparency:
David F. Archer, MD, has received grants for clinical trials from Wyeth-Ayerst Laboratories, Ortho Pharmaceutical, Organon, Inc, Lilly, Schering Plough, Berlex Laboratories, Pharmacia Corp, and TAP; he is a consultant to Wyeth-Ayerst Laboratories, TAP, Organon, Inc, Lilly, Pharmacia Corp, and Schering Plough; and he serves on the speakers’ bureaus of Wyeth-Ayerst Laboratories, Organon, Inc, Pharmacia Corp, and Lilly.
One way to read this long list of every major drug company is: “This guy has worked for so many drug companies he couldn’t possibly have a favorite.”
Wanna bet?
In article after article, Archer has promoted Wyeth’s products by using his name as good science seal of approval. DesignWrite, a medical communications company hired by Wyeth, conceives of the articles, writes them and then asks Archer to sign his name. From the Drug Industry Document Archive, here’s DesignWrite’s schedule showing when Archer’s contraceptive paper was going to be published, one of eight DesignWrite projects that had been accepted for publication.
It might help explain how Archer has published more than 200 studies. This is an enviable amount among researchers, some of whom work for more than two years just to get one paper published. When most of the work on a research paper is already done, though, and all you have to do is submit the finished product to a journal, it’s not hard to publish frequently.
The outlines are written with the help of DesignWrite and Wyeth employees long before Archer or any other authors are contacted. And they read like actual drafts. Did DesignWrite and Wyeth’s involvement affect Archer’s conclusions in that contraceptive study? That’s something I’ll deal with in a future post.
For an article titled, “Efficacy of Combination Conjugated Equine Estrogen and Trimegestone on the Incidence of Endometrial Hyperplasia,” OCC North America, another medical communications company, put together a four-page outline that provided everything Archer and the other authors needed to help sell Wyeth’s key messages.
Published in 2005, Archer co-authored another paper titled “Endometrial effects of bazedoxifene acetate, a novel selective estrogen receptor modulator, in postmenopausal women.” The researchers concluded:
Bazedoxifene at dosages up to 40 mg/d was well tolerated and did not stimulate the endometrium. The significant decreases in endometrial thickness and decreased uterine bleeding observed with doses of 30 and 40 mg/d as compared with placebo suggest endometrial antagonism, representing a novel characteristic not previously associated with any selective estrogen receptor modulator.
Six of the seven researchers listed as authors on this paper had worked with DesignWrite/Wyeth in the past. This paper made it clear where the authors were coming from by listing the lead author’s affiliation as Wyeth. This is a rarity. Out of Archer’s 200+ papers, only three in the National Institutes of Medicine’s PubMed database list Wyeth as the affiliation of the lead author:
June 1998 – “Amenorrhea frequency with continuous combined hormone replacement therapy: a retrospective analysis. Menopause Study Group.”
June 2005 – Endometrial effects of bazedoxifene acetate, a novel selective estrogen receptor modulator, in postmenopausal women.”
Archer also is a gatekeeper for other researchers. He is the editor of Menopausal Medicine, published by the American Society for Reproductive Medicine. He also serves on the editorial board of Menopause, the journal of the North American Menopause Society. How closely can a conflicted editor be expected to guard against authors with conflicts?
Right after the Women’s Health Initiative findings, Menopausal Medicine published an article by another frequent DesignWrite collaborator, Dr. James V. Fiorica. Titled “Mammographic breast density and hormone replacement therapy,” it said:
Use of hormone replacement therapy (HRT), including therapy with unopposed estrogen or estrogen plus progestin, increases breast density in some postmenopausal women shortly after the initiation of treatment. This change in breast density has led to some speculation that mammographic detection of cancer may be compromised in HRT users. However, researchers have shown that detection of breast cancer is not impaired by HRT use. Moreover, advances in mammographic technology are improving the sensitivity and specificity of even the most difficult-to-read mammograms.
To underscore the point, Archer called out the key drug company message in his “From the Editor” note:
James V. Fiorica, M.D., presents the current status of hormone therapy and mammography density. He concludes that although hormones increase mammographic breast density, there is no evidence for a decreased or impaired detection of breast lesions.
This sounds like solid science, right? It acknowledges the biological effects of HRT on breast density but then explains how those effects relate to breast cancer. But where are Fiorica’s references? Unlike the other authors in the newsletter, one of whom cited 30 other papers, Fiorica’s references are not listed.
Here’s the biggest omission. Fiorica, Archer and the newsletter fail to disclose that the article actually was written by DesignWrite/Wyeth. Instead, it says at the very end, “The author has revealed the following potential conflict of interest: Speaker: Wyeth.” And Archer apparently was playing on both sides of the field. He was supposed to be, as the journal editor, the ultimate arbiter of the strength of the submissions to Menopausal Medicine. But, as documents in the Drug Industry Document Archive show, he also was working directly with DesignWrite on tailoring the article. The history of how this article evolved can be seen here.
Make no mistake, research papers written by communications companies like DesignWrite on behalf of drug companies are marketing first and foremost. DesignWrite’s “Publication Planning and Management” statement makes it clear:
A scientific publication plan is as vital as a carefully designed media plan in overall product marketing
Goal is to establish a diverse published database that supports promotional and scientific efforts in all appropriate markets
Assure publication of key available data for launch and postlaunch indications
Present substantial documentation with data demonstrating the benefits of the Premarin Family of Products
If you believe that these companies see the researchers as independent voices helping the companies guide their scientific endeavors, read this email from one DesignWrite writer to a Wyeth executive trying to find friendly researchers to sign ghostwritten work:
We’ve had good experience with Pinkerton, Shoupe, Dorin, Carr, Lobo, Gallagher, Archer, and Utian as authors. Some are more hands on than others, but all were responsive and provided good feedback. The key is to have a lead author who is entrenched in the data and can be firm with the co-authors regarding deadlines.
Regarding your query for additional authors, our suggestion would be to have your medical communications company do a literature search on the other investigators to see their recent publications. A lit search would also be a useful for identifying additional Prem TMG advocates.
Don’t take Antidote’s word for it. Go to the Drug Industry Document Archive and search for Archer’s name.