Wednesday, April 16, 2008

Ghosts Come Home to Roost

We posted quite a bit starting in 2005 about ghost-writing (see post here with links backward).

Back then it became evident that a particularly pernicious type of ghost-writing was much more prevalent than anyone seemed to realize.This sort of ghost-writing has several important elements.

  • Commissioned by Those With Vested Interests - The writing is commissioned by an organization with a vested, usually commercial interest, e.g., a pharmaceutical company.
  • Directed to Support Vested Interests - The ghost-writer, perhaps a free-lancing medical writer or employee of a medical communication company, writes an article meant to support that organization's interest, often by setting the stage for the organization's new products. For example, a pharmaceutical company about to market a new drug may commission articles that makes the condition for which the drug is used seem particularly common or important, or which emphasizes the negative aspects of current treatments.
  • Fronted by an "Expert" - Finally, an expert, often a well-known academic, agrees to become the article's ostensible first author.

In 2007, we posted to summarize an article on ghost writing which appeared in respected, but not widely circulated journals. Moffatt and Elliott made two clear points:

  • Ghost writing is common.
  • Ghost writing is wrong.

They also suggested some important things that ought to be done.

  • Universities need to treat the practice of signing on to ghostwritten journal articles as a case of academic misconduct.
  • Lawyers should start naming ghostwriters and sham authors as defendants in litigation against the pharmaceutical industry.
  • There needs to be a standing committee, task force, or office with an established institutional home whose job is to gather information about potential cases of ghostwriting, to sanction authors who have been determined to participate in ghostwriting, and to disseminate information about ghostwritten papers to the public.
  • There needs to be an effective strategy for identifying and discouraging ghostwriting.

Of course, this issue got little attention, and none of the measures noted above were implemented. Until yesterday....

Yesterday, a major article appeared in JAMA which described a case-study of ghost authorship and ghost writing of publications related to the drug rofecoxib (Vioxx, Merck, now withdrawn from the market) that used internal company documents made public in the course of litigation about alleged injuries due to Vioxx. [Ross JS, Hill KP, Egilman DS, Krumholz HM. Ghost authorship and ghostwriting in publications related to rofecoxib: a case study of industry documents from rofecoxib litigation. JAMA 2008; 299: 1800-1812. Link here.]

This article should be required reading not just for anyone interested in ghost writing, but for anyone concerned about what has gone wrong with health care. The main points of the paper were:




Merck used a systematic strategy to facilitate the publication of guest authored and ghost written medical literature. Articles related to rofecoxib were frequently authored by Merck employees but attributed first authorship to external, academically affiliated investigators who did not always disclose financial support from Merck, although financial support of the study was nearly always provided. Similarly, review articles related to rofecoxib were frequently prepared by unacknowledged authors employed by medical publishing companies and attributed authorship to investigators who often did not disclose financial support from Merck.

The authorship pattern observed within these documents suggests there was a widespread practice of inappropriately attributing authorship to academic authors and a failure to disclose relevant financial relationships.

Unlike the stories of ghost authorship we discussed in 2005, the JAMA article got a tremendous amount of press coverage. I should note that this included some rebuttals from Merck and some of those identified as "front" authors by the JAMA article. Here is a sampling, first of the authors:


The fact that the draft was written by a Merck employee for later discussion by all the authors does not in of itself constitute ghostwriting [Dr Louis Kirby, identified as an added academic author of one article, quoted by Stephanie Saul in the NY Times.]

But Steven H. Ferris, a neuropsychologist at New York University School of Medicine who is listed as the second author, said [the charges of ghost authorship were] ... not true. He said he was on a committee that reviewed the clinical records of 195 patients who received diagnoses of Alzheimer's during the study -- a task that took many hours, and for which he was paid.

'I was directly involved in a very substantive way,' he said this week. 'If an entity like JAMA is going to make an effort to expose a problem, they better get their facts straight. It is harmful if they don't.' [per the Washington Post.]
Having had a 20 plus year previous career in academic medicine, I can state with conviction that first, second, and third authors of major research papers published in important journals are expected to have been the people who conceived, designed, and implemented the study, analyzed its results, and were primarily responsible for the interpretation of thse results. Note that neither "author" above described his role in the trial in such terms.

Most of Merck's initial response seemed to come from its lawyers, for example,


A spokesman for Merck's legal team dismissed the JAMA authors as 'people in the pay of trial lawyers.' [per the Washington Post]

[James] Fitzpatrick, Merck's attorney, said: 'It is correct that Merck would sometimes use an outside company to compile the literature in a field and do the first draft, much the way a professor would use a research assistant to do the same thing.' [Per the Washington Post.]

Jim Fitzpatrick, a Merck outside lawyer, said the company agrees that authorship and financial relationships should be properly disclosed. The company adopted guidelines in 2003 to commit to further transparency in its publications, he added. Merck acknowledged that it sometimes worked with outside medical writers 'to facilitate the publication' of the studies, but said academic researchers 'were involved with the drafting and review of the papers that bear their name.'

Merck research chief Peter Kim said, 'We are disappointed that such false and misleading statements about Merck from trial lawyers have made their way into a medical journal.' [per the Wall Street Journal.]

A Merck legal spokesman said the company sometimes uses outside companies to draft articles that summarize research on its drugs. 'That's a common evolving practice in the industry,' said spokesman Kent Jarrell.

'We do not consider that ghostwriting,' added Jim Fitzpatrick, lead counsel in Merck's defense against numerous lawsuits over Vioxx. He said the company expects that the person recruited to sign the article 'would carefully review and make sure that the paper accurately reflected his or her scientific opinion.' [per the Boston Globe.]

Note that none of these responses provided anything concrete to refute the major points of the article, that Merck or MECCs in its pay found "front" authors for the clinical trial report articles who were not, in fact, the people who conceived, designed, and implemented the trial, and analyzed its results and crafted their interpretation. Doing minor edits of a draft someone else writes does not an author make.

The Ross et al article was accompanied by an editorial by the Editor in Chief and Executive Deputy Editor of JAMA [DeAngelis CD, Fontanorosa PB. Impugning the integrity of medical science: the adverse effect of industry influence. JAMA 2008; 299: 1833-1835. Link here.]

Its main conclusions were:


The profession of medicine, in every aspect—clinical, education, and research—has been inundated with profound influence from the pharmaceutical and medical device industries. This has occurred because physicians have allowed it to happen, and it is time to stop.

What are the lessons from the 2 articles in this issue of JAMA, from other publications that have examined related issues, and from extensive experience with how clinical research has been manipulated by for-profit companies? First, manipulation of studies and misrepresentation of study results could not occur without the cooperation (active and tacit) of clinical researchers, other authors, journal editors, peer reviewers, and the FDA. Second, public trust for clinical research is in great jeopardy especially when the extent of how widespread such practices have become is unknown. Although we truly believe that the vast majority of researchers and other authors are honest and have the highest scientific integrity, manipulation of studies and publications by the pharmaceutical and medical device industries is either increasing or there has been more exposure of these practices. Third, in addition to clinical research, clinical practice and medical education also are greatly influenced by for-profit companies. Drastic action is essential, and cooperation of everyone involved in medical research, medical editing, medical education, and clinical practice is required for meaningful change to occur.

Some of the press coverage included more vivid comments by DeAngelis.


I consider that being scammed. [Referring to ghost written article in JAMA, per article by Stephanie Saul in the New York Times.]

The manipulation is disgusting. I just didn't realize the extent. We're the ones who have allowed this to happen. Now we've got to make it stop. [per the AP.]

[Ghostwriting is] a terrible form of prostitution. We've given up the profession. We've got to get it back. [Per the Philadelphia Inquirer.]


DeAngelis and Fontanarosa had a list of 11 detailed action items, many of which were relevant to those suggested by Moffatt and Elliott above. However, item 11 was radical.


Individual physicians must be free of financial influences of pharmaceutical and medical device companies including serving on speaker's bureaus or accepting gifts.

Maybe this time someone will be listening.

We on Health Care Renewal have been talking for years now about how clinical research and medical education have been influenced and manipulated to promote vested interests. It now appears that a substantial portion of the clinical evidence base and a substantial amount of medical education have been so undermined.

Dr DeAngelis is right. We have given up medicine and now we have got to get it back. If we don't, we will be left with unimaginably expensive health care that does little good except to the pocket books of the well connected.

ADDENDUM (16 April, 2008) - On the PharmaLot blog, Ed Silverman noted that Dr Ferris (see above) seemed to have trouble recalling his actual role in the Vioxx trial. Also on that blog, Ed Silverman noted that Senator Grassley is looking into the role of one of the MECCs mentioned in the Ross et al article.

No comments:

Post a Comment