Boo! Wyeth And Its Ghostwriting Practices
16 CommentsBy Ed Silverman // September 8th, 2010 // 7:54 am
Two years ago, an investigation disclosed that Wyeth used a ghostwriting firm to generate material used to promote its hormone replacement therapies. By then, of course, the meds were linked to breast cancer in the 2002 Women’s Health Initative study. But the disclosure prompted a US Senate probe and has since been widely cited as an instance in which pharmaceutical marketing corrupted the process by which legitimate medical info is supposed to be disseminated (background).
But just how extensive was the Wyeth ghostwriting? Well, between 1997 and 2003, a firm hired by Wyeth called DesignWrite generated more than 50 peer-reviewed publications, more than 50 scientific abstracts and posters, journal supplements, internal white papers, slide kits, and symposia to promote its Premarin and Prempro meds. There were other firms, but DesignWrite was used most often and was paid between $20,000 and $25,000 for each of 20 review articles (you can read the publication plan for low-dose Prempro here, for instance).
“The beauty of this process is that we become your postdocs,” Karen Mittleman, a DesignWrite employee who supervised medical writers, wrote in a 2001 email to an academic author. “We provide you with an outline that you review and suggest changes to. We then develop a draft from the final outline. You have complete editorial control of the paper but we provide you with the materials to review/critique.” The author was puzzled over the concept of authoring, but not writing a paper.
All this and more is courtesy a paper published in PLoS Medicine, which reviewed approximately 1,500 documents - emails, contracts, internal memos, depositions - that were culled from litigation brought by some 14,000 women and their families against Wyeth - now owned by Pfizer - and obtained by PLoS and The New York Times last year. The paper was written by Adriane Fugh-Berman, a researcher at Georgetown University Medical Center in Washington DC, who has also been a paid expert witness for plaintiffs against Wyeth and Pfizer.
For the curious, the documents make interesting reading, so look here and search by using the name of a drug. Other drugmakers have also been cited for ghostwriting, most recently, GlaxoSmithKline in connection with its Avandia diabetes pill (see this) and Merck, which employed the practice to promote its Vioxx painkiller before it was yanked in 2004 over links to cardiovascular risks (see this). Although some industry defenders argue the recent disclosures refer to dated examples, industry critics say the practice may persist, but is not necessarily known because most instances do not involve high-profile litigation or government investigations.
“Medicine, as a profession, must take responsibility for this situation,” write Fugh-Berman. “Naivete is no longer an excuse. Perhaps physician-investigators should create and uphold a standard where relationships with industry are regarded as unsavory rather than sought after. Academic institutions and medical journals should take a hard line on ghostwriting. Patient care will benefit if physicians draw together as a profession to denormalize relationships with industry and avoid the role of corporate pawns in the future.”
In a statement, Pfizer says reiterates that Fugh-Berman is a paid expert “and even with her critical perspective, she could not establish that there were inaccuracies in any of the peer reviewed articles, or that their authors relinquished control over their work. The PLoS article breaks no new ground and fails to acknowledge the significant changes in policy undertaken by Pfizer and other companies to help strengthen disclosure in connection with medical literature.
“Most importantly, this article completely - and conveniently - ignores the fact that the published manuscripts were subjected to rigorous peer-review by outside experts on behalf of the medical journals that published them, and that their integrity and scientific rigor has even been recognized by multiple courts. For example, in Bailey v. Wyeth, New Jersey Superior Court Judge Jamie Happas wrote on July 11, 2008: ‘There is no dispute that the articles were subject to a rigorous peer review process and were factually and medically sound.’
“Pfizer has a publicly posted policy on authorship, which, among other things, ensures that the named authors of each article, typically the principal investigators, have sole supervision when preparing articles about Pfizer-sponsored trials. Pfizer adheres to the authorship criteria established by the International Committee of Medical Journal Editors (ICMJE) and the PhRMA Principles on Conduct of Clinical Trials and Communication of Clinical Trial Results and trains both clinicians and staff on these guidelines. For articles in which Pfizer is involved, authors are required to acknowledge the contributions of any non-authors assisting in the preparation of articles.
“As a science-based company, Pfizer places the utmost importance on the integrity of scientific research and authorship of medical literature. Medical writing companies assisted authors only in drafting manuscripts, and authors themselves had total control of the content of these papers, which were always based on sound science.
“In February 2009, Pfizer, as part of its commitment to increased transparency and public candor, became the first biopharmaceutical company to commit to disclosing publicly its financial relationships with physicians, medical organizations and patient advocacy groups payments, including fees for speaking and consulting and investigators who conduct clinical research.
“In 2006, Wyeth adopted a policy mandating that authors become involved early in the publication process and that any financial assistance by Wyeth or contributions by medical writers be acknowledged in the published text.”
Ghost from Flickr Creative Commons mattwi1s0n
pharmavet®
You know that this was a very high priority for Wyeth when they were willing to pay 3-4X the going rate for a a series of REVIEW articles. In the “ghostwriting business”, back in tose days, even an original research article, with data analysts, etc. would notmally fetch no more than $10K.
Justice in MI
Haven’t yet read the Fugh-Berman article, but the original document release was “impressive”–Designwrite pitching itself to Wyeth about where it could place pro-HRT articles, how to “neutralize” concerns about breast and endometrial cancer (especially via oncology journals), and how fast they could turn things over.
Good example of what one might call horizontal prostitution, or perhaps more simply, “whorizonatlism.”
Justice in MI
Spellcheck: Whorizontalism.
andty
how many politicians write their own speeches?
Ho's R Us
Wow. Andty, do you mean to equate a political speech with publication in a medical journal, supposedly some version of “science”?
If all communications are equal–political speeches, advertising, medical journal articles, etc.–than we are all whores (and “johns”) indeed.
Richard
Re: Andty,
Politicians are supposed to be representing the voting public and their interests. Shouldn’t they at least have to disclose who wrote their speech.
Second, an article in a medical journal goes through at least some type of peer review before acceptance and publication. You can’t say that for a politicians speech.
Mike
So what is really worse?
A ghost-writer that assists a busy clinician/researcher in getting his or her opinion/data published in a peer-reviewed paper in a timely fashion OR a cutting-edge research paper written by the graduate student assisting the busy professor that gets published and then retracted for falsifying or fudging data.
Can we all say stem cells!
RealityCheck
It is important, I think, to distinguish between ghostwriting in general and ghostwriting the aim of which is to “dismiss/distract” (to quote a Wyeth internal memo) serious risks.
The DesignWrite 1997 proposal to Wyeth reiterates several times that, among its core goals, was to minimize the then known risks of HRT re: endometrial cancer especially. This is said explictly.
Twenty years earlier, there is also a document summarizing an meeting between company officials and FDA in which it is noted, in several places, that FDA believes the company has been “obfuscating” cancer risks of HRT, and essentially does not trust it to do otherwise.
LF Velez
I have to wonder: Would current disclosure rules have helped crack the wall of obfuscation any sooner? If the DesignWrite writer who drafted the articles had to be cited as the primary author, and the funding source identified clearly as Wyeth, would anyone have thought “Gee, 50 articles all touting the magic of Prempro, all funded by the manufacturer. Could they perhaps be protesting too much about something?”
It’s easy from this end of history to say that HRT was a bad idea. It may
be that excellent PR kept people from asking hard questions sooner, but did
anyone stake their reputation on the opposing side before it became the
obvious “winner” in the sphere of public opinion? Would any of the reviewers who registered skepticism about these claims be willing to identify themselves? Wyeth had been putting their side of the story about hormones and their health effect for longer than any contact with DesignWrite — that’s their duty to their stockholders [I think the idea that pharma is some special business that is more concerned with human health than the bottom line has been put to rest by now, yes? Virtually every other drug on the market has its reputation tended and promoted in the same way...and if it had turned out that HRT really did do all the marvelous things Wyeth, Pfizer, and other companies have claimed, we wouldn't even be having this conversation: It's because people feel tricked about this drug that we are looking for someone to blame for having "fallen" for the HRT story for so long.]
Aside from all this, how can journal editors simultaneously insist that
medical writers don’t make significant contributions to content [therefore we shouldn't be considered authors] AND ALSO that we are nefariously controlling the content to the point of warping medical practice? Surely if medical writers have more power over the course of medical history than the peer review process, _that’s_ worth authorship status!
[sigh]
harpy
I don’t think it’s because people feel “tricked” about this drug, LF Velez. I think people are upset because they or a loved one got cancer (and heart attacks and strokes) and some of them died. menopause may not be a lot of fun, but I’ve never heard of it killing anyone. and the people to blame are easy to find - Wyeth (now Pfizer), DesignWrite, and any doctor that allowed his/her name to be used to support research they had no way of knowing was true.
bmartinmd
Yes harpy, I think the outing of the “john” (ie, the physician-author) is warranted in these cases. (Although it’s not entirely parsed out by Fugh-Berman how much each physician-author contributed to each article or changed its tone. In some cases, the authors clearly balked at the overbearing nature of DesignWrite.)
I also think it’s important to distiguish between the ghostwriting of reports of randomized, controlled trials (RCTs) (and whether they credit pharma-employee authors) and reviews or commentaries. And among the latter, it’s important to distinguish between reviews and editorials that accompany the publication of RCTs, which can be very influential, and those that appear in company-sponsored supplements–which have little, if any, influence on practice, IMO, because they are summarily tossed.
Fugh-Berman concludes, “Marketing messages in credible journals have almost certainly contributed to widespread use of HT among millions of women who had no medical indication for the drug.” But she does so without evidence and without stressing the relative influence of various article types and the context of their publication. Moreover, I think she should have broken down her article assessment more distinctly on the basis of date: pre- and post- the 2002 publication of the Women’s Health Initiative data.
Justice in MI
re: LF Velez comment, I guess the bottom line is whether a cat & mouse approach to integrity is appropriately all that defines a pharma company’s obligations (to shareholders).
If so, all the stuff that people like Jeff Kindler have been saying over the past year should be saying with the same knee-jerk cynicism that has so often accompanied such statements in the past.
So is that, indeed, the “mature” response?
Justice in MI
second “saying” should be “taken”….long day.
bmartinmd
Re: LF Velez comment also. The idea that postmenopausal HRT was a good idea was pretty much blown sky-high with the publication of the Women’s Health Initiative study in 2002 (and to a much lesser extent with HERS in 1998). But it wasn’t just Wyeth balking at the news. Physicians, who for years prescribed HRT, were reluctant to completely 180 their practice (and acknowledge they’d been wrong all along). It’s hard to dramatically alter the status quo of medical practice on such a massive scale, and while Wyeth may have attempted to stem the change, don’t discount the hurdle of an ingrained mindset.
Justice in MI
Agree that physicians have their own responsibilities, and problems, in responding to new information. But it is also obvious that when a company goes out of its way to use smoke and mirrors, HCPs will be that much less likely to change rx’ing habits.
This from a _1976_ FDA response to Ayerst–25 years before the Nurses’s Health Study:
1. “The above letter [Ayerst dear doc re: endometrial cancer] is warped in tone and intended to obfuscate issues rather than to highlight new information related to risk.”
2. “…the FDA does not trust Ayerst to write a reliable letter…”
3. The Ayerst letter “…has incensed the FDA at all levels including the Commissioner of Food and Drugs.”
So here we have some specifics rather than platitudes. For its own part, Ayerst claimed to be taking full responsibility for the publication of reliable information about its product.
So, again, I ask–Is it the “mature” response to assume such claims, in such contexts, are inherently bs when they come from whatever company? And [sigh] to expect otherwise is just, well, babyish.
pharmavet®
JiM, Ayerst may not have had the best scientists, but their legal team excelled over everyone else’s. I’ve worked with some of their outside council in the past who, for example kept Wyeth-Ayerst-AHP bulletproof from generic competition for Premarin for over two decades. Basically, they were able to lure FDA attorney’s away from their slave wage jobs in Rockville, and, at $500/hour and many, many billable hours later made Premarin a multibillion dollar product and themselves multimillionaires in the process.