Merck’s Ghostwriters, Haunted Papers and Fake Elsevier Journals

8 05 2009

What is the purpose of publications? (…) The purpose of data is to support, directly or indirectly, the marketing of our product.” [1, 2]

pmed0020138g001It is well known that studies with significant positive results are easier to find than those with ‘negative’ results. This so called publication bias can arise from the tendency to submit or accept manuscripts that have a positive rather than a negative or neutral result. It can also be the consequence of deliberately overemphasizing positive results or even worse: the results can be “embellished”, (partly) faked or negative results can be “hidden

In fact, pharma-sponsored trials rarely produce results that are unfavorable to the companies’ products [3, 4, 5]. For instance, none of the published 56 trials of  NSAIDs in arthritis identified by Rochon et al in 1994 [3] had outcomes that were unfavorable to the company that sponsored the trials. Another study showed that studies funded by a company were four times more likely to have results favorable to the company than studies funded from other sources [1, 4]

Ghostwriters, who write articles that are officially credited to another person, are part of the tactics. Ghostwriters may be hired by companies to write articles for medical journals that appear under the names of scientists who didn’t substantially contribute to the paper. In extreme cases pharmaceutical companies and their agents control or shape multiple steps in the research, analysis, writing, and publication of articles. This so called ghost management can be outsourced to MECC’s, medical education and communication companies.

All the above approaches, -and more- are said to have been used by Merck to sell their Vioxx (rofecoxib) pills, the blockbusting painkiller, that could cause heart attacks and strokes [6]. Merck knew, but didn’t disclose (all) these adverse effects*. Later it appeared that many Vioxx- manuscripts were prepared by sponsor employees (ghost writers), but attributed to academic investigators who did not always disclose industry financial support. Distancing himself from one such article, first author Jeffrey Lisse said in an interview that:

“Merck designed the trial, paid for the trial, ran the trial…Merck came to me after the study was completed and said, ‘We want your help to work on the paper.’ The initial paper was written at Merck, and then it was sent to me for editing” [NY-times -[2005].

And although Merck has “voluntarily” withdrawn Vioxx from the market in 2004 and has agreed to pay billions to settle lawsuits in the US, the Vioxx-ghost keeps hunting Merck (and us).

In a few weeks 3 news-items have crossed my eyes.

A. The Guardian ( May 4) mentioned that Merck refused to compensate hundreds of Britons who have suffered serious cardiovascular  problems while on Vioxx.  Ministers apparently backed down from supporting these people after lobbying by the company.

B. May 1st NewsInferno com reported that Merck was accused of hiring a ghostwriter for a Circulation paper (2001) to minimize issues linked to Vioxx’s safety, while the well known cardiologist Dr. Marvin Konstam agreed to act as lead author. This was revealed by Prof. Jelinek during an Australian lawsuit against Merck.

C. The above news story was covered by Australian Newspapers including “the Australian“. In its article on the lawsuit, the Australian also devotes one sentence to a fake Elsevier/Merck journal. It says:

“The drug company also allegedly produced an entire journal — called The Australasian Journal of Bone and Joint Medicine — and passed it off as an independent peer review publication.”

It is this sentence that has caused a tsunami, starting with the Scientist, via blog.bioethics.net to  many other blogs of researchers, publishers, librarians and to newspapers. “Everybody” was alarmed.

What were the allegations? Are they all true? Who is to blame? Merck or Elsevier? Most importantly: is it an isolated incidence, something completely new and what is its impact?

Points addressed by the Scientist (mainly based on interviews, i.e. with George Jelinek)

  1. Australasian Journal of Bone and Joint Medicine, is published by Exerpta Medica, a division of Elsevier
  2. This Journal is not indexed in the MEDLINE database and has no website.
  3. It had the looks of a peer-reviewed medical journal, but contained only reprinted or summarized articles
  4. Most of the articles presented data favorable to the Merck products Fosamax (for osteoporosis) and Vioxx.
  5. So called “review” articles only cited one or two references. Even a meta-analysis contained 2 references, one of which referring to a real meta-analysis.
  6. The articles are “simply a summary of already published articles”
  7. There are several ads for Fosamax and Vioxx.
  8. It is unclear who wrote the editorials
  9. One member of the editorial board, Peter Brooks said that he didn’t ever get manuscripts to review while on the board. Neither was he paid for his role.
  10. There is no disclosure of company sponsorship.
  11. Merck paid an undisclosed sum to Elsevier to produce several volumes (confirmed by Elsevier).

According to a statement of Merck (see pdf on their website):

“The Australasian Journal of Bone and Joint Medicine (..) was published by the medical publishing company Elsevier. Merck Sharp & Dohme Australia understood that Elsevier envisaged the complimentary publication would draw on the vast resources of Elsevier, publishers of many leading peer-reviewed journals including Lancet, Bone, Joint Bone Spine and others, to deliver novel and timely full-text articles and abstracts to physicians.”

In the same PDF Merck states that “ghostwriting” allegations concerning the 2001 Circulation paper about VIOXX [item B] are false and that professor Jelinek has witdrawn his accusation under cross examination. According to Merck, the lead author Dr. Marvin Konstam, was in fact very much involved in the study. Indeed, according to the Heartwire, Konstam maintained he acted properly. He  takes full responsibility for everything he has published.

Elsevier acknowledged the concern that the journal didn’t have the appropriate disclosures,” and although they said they had no plans in looking further into the matter, Elsevier disclosed today that in total 6 such fake Australasian Journals were produced (see Scientist).

Now what? An isolated blunder by staff of the Australian Branche of Elsevier who published a fake peer review while Elsevier headquartes and Merck were totally unaware?

First, although I don’t want to triviliaze the affair, obviously this Journal does not pretend to be a peer reviewed paper (i.e. see this pdf, obtained by the Scientist). Any doctor who even considers it to be a peer reviewed paper must have very little experience with critically reading of peer reviewed papers. It is clear from the start that all articles are just copied from other (Elsevier) Journals, the citations are given, articles are classed to type (in black boxes at the tope) and the so called meta-analyses just describes another meta-analysis, which is cited.

The editorial board is called “Honorary”. The advertorials and the repeated mentioning of Merck drugs makes it immediately clear that this Journal is just a so-called throwaway. True, it should have been disclosed at the front page and the Journal’s name and lay-out might suggest otherwise at first glance. And to me as a librarian it is particularly strange that there was an annual subscription for institutions of $250. Throw-aways are usually for free. Furthermore it is not included in Science Direct nor the usual bibliographic databases.

As a matter of fact, this Journal is what you would expect from an “Excerpta Medica Journal”: an excerpt of various articles. At least that’s what the name suggests and that’s what I remember from the old fashioned Excerpta Medica abstract journals I browsed as a post-doc.

But it is remarkable that “the reliable and authorative” Elsevier, publisher of journals like the Lancet, lends itself to a biased publication of articles that only serve as promotional material? Surely this is an exception?

Well, whereas Elsevier itself has dismayed the Lancet by sponsoring one of the largest military exhibitions in the world (CMAJ 2007), its medical and health sciences division Excerpta medica is clearly a separate business. On the Elsevier website 41 titles of Excerpta Medica are listed, but none of the Australian Excerpta clones. Here it says that:

Every journal contains bibliographic references and abstracts summarizing original articles from primary research and clinical journals. The records are carefully selected from 4,000 journals from 70 countries around the world, which makes the Excerpta Medica Abstract Journals very comprehensive.

The home page of Excerpta Medica states that it is an “Elsevier Business”, a strategical medical communications agency, partnering with their clients in the pharmaceutical and biotech industries to educate the global health care community to enable them to make well informed decisions (copied from EBM definition of Sackett, hé?)

excerpta

Under the heading “strategic planning” it is written that “Our relationship with Elsevier allows us access to editors and editorial boards who provide professional advice and deep opinion leader networks” ….(!!)

I’m not the first one noticing this.

In 2007 the same link was given by the PLOS-paper about ghost management[1], discussed above..

Here Excerpta is mentioned as an example of a MECC.

And not only in this paper. Both a Medscape[7] and a Perspectives in Biology and Medicine article[2] mention the role of Excerpta as a MECC. A citation from the latter:

Recovered documents show that the pharmaceutical company Wyeth hired the MECC Excerpta/Medica to produce several scientific papers on the dangers of obesity and on obesity treatment as part of their marketing strategy for Fen-Phen. Mundy documents that Wyeth paid between $15,000 to $20,000 for Excerpta to prepare each article, of which $1,500 would go to the “named author” as an honorarium. Some completed papers, simply listed as “author to be determined,” lacked a “named author,” while others had made their way in to print or were under review. One doctor, Dr. Richard Atkinson, was so pleased with the arrangement for “Therapeutic Effects of Dexfenfluramine: A Review” that he wrote a thank you note to Excerpta/Medica saying,“Let me congratulate you and your writer. . . . Perhaps I can get you to write all of my papers for me” (Mundy 2002, p. 164).

And Medscape:

What made Excerpta Medica such an inspired choice is that it is a branch of the academic publisher, Reed Elsevier Plc., which publishes many of the world’s most prestigious science journals. Excerpta Medica manages two journals itself: Clinical Therapeutics and Current Therapeutic Research. According to court documents, Excerpta Medica planned to submit most of the articles it produced to Elsevier journals. In the actual event, Excerpta managed to publish only two articles before Fen-Phen was withdrawn from the market in 1997. One appeared in Clinical Therapeutics, the other in the American Journal of Medicine (another Elsevier journal). In neither case did the authors of the articles disclose that they were paid by Excerpta Medica. So clean was the laundering operation, in fact, that many of the authors did not even realize that Wyeth was involved.

By the way Fen_Phen was not particularly effective, and was linked to valvular heart disease, leading to the death of hunderds of people. Even after withdrawal Wyeth spent $100 million on public relations to convince the public that the response had been overblown.

Hereby I do not want to suggest that Excerpta has played a similar role in the Vioxx case, but it does illustrate that Excerpta is a MECC with dangerous principles as it organized the ghostwriting for Wyatt elaborately, using its connections with Elsevier in a very nontransparent way.

I also don’t want to suggest that the followed procedure is unique for Excerpta. Several other MECC’s follow the same approach. For many other examples see the references below, especially [1, 2, 7]. It is really tarnishing. And worth a reading.

However, In my opinion we have to fear more from the strategic publication planning of the MECCs in authentic journals then the fake Australian Excerpta series. Firstly, because the known Journals are far more trustworthy and have far more impact than the throwaways. Secondly because the phenomenon of ghostwriting is widespread, also among “first class Journals”. A conservative benchmark for ghostwriting of papers published in biomedical journals is roughly 10%[2], but in particular cases the percentage may be much higher [1]. This has caused Richard Smith, former editor of the BMJ to sigh that “Medical Journals Are an Extension of the Marketing Arm of Pharmaceutical Companies.”

Anyway, I bet that my doctor did not describe Vioxx for my backache 10 years ago because he read “The Australasian Journal of Bone and Joint Medicine”. Rather he must directly or indirectly have learned from the results of the VIGOR trial published in the New England Journal of Medicine.

With respect to the citation I began with, it is not from Merck, but from Pfizer as an answer to the question: “What is the purpose of publications?” on the header on a Pfizer sales document (2000)

References

  1. Sismondo, S. (2007). Ghost Management: How Much of the Medical Literature Is Shaped Behind the Scenes by the Pharmaceutical Industry? PLoS Medicine, 4 (9) DOI: 10.1371/journal.pmed.0040286
  2. Moffatt, B., & Elliott, C. (2007). Ghost Marketing: Pharmaceutical Companies and Ghostwritten Journal Articles Perspectives in Biology and Medicine, 50 (1), 18-31 DOI: 10.1353/pbm.2007.0009
    The whole issue is dedicated to this topic: Perspectives_in_biology_and_medicine.
  3. Rochon PA, Gurwitz JH, Simms RW, Fortin PR, Felson DT, et al. A study of manufacturer-supported trials of nonsteroidal anti-inflammatory drugs in the treatment of arthritis. Arch Intern Med. 1994;154:157–163. [PubMed]
  4. Lexchin J, Bero LA, Djulbegovic B, Clark O. Pharmaceutical industry sponsorship and research outcome and quality. BMJ. 2003;326:1167–1170. [PubMed]
  5. Smith R. Medical Journals Are an Extension of the Marketing Arm of Pharmaceutical Companies. PLoS Med. 2005 May; 2(5): e138. Published online 2005 May 17. doi: 10.1371/journal.pmed.0020138.
  6. Ross JS, Hill KP, Egilman DS, Krumholz HM. Guest Authorship and Ghostwriting in Publications Related to Rofecoxib: A Case Study of Industry Documents From Rofecoxib Litigation JAMA. 2008;299(15):1800-1812.
  7. http://www.medscape.com/viewarticle/492877

Photo Credits

Margaret Shear, Public Library of Science, see [6]

*Merck has never admitted that Vioxx could cause a cardiovascular risk, but the general idea is they just covered it up.








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