Ensuring that medical journal articles presented Zyprexa study results in a positive light was one way for Lilly to reach its sales goal, company officials said in its plan, according to the documents.
To do that, Lilly officials hired ghostwriters to prepare submissions to journals such as Progress in Neurology and Psychiatry, according to the unsealed documents.
The article then described how Lilly marketers set up a ghost-written article.
'The paper for the Progress in Neurology and Psychiatry supplement has been completed and sent to the journal for peer review,' Kerrie Mitchell, an employee of the public relations agency Cohn & Wolfe, wrote in a Feb. 23, 2001, e-mail to Michael Sale, a Lilly marketing official. The message was among the unsealed files.
'We ‘ghost’ wrote this article and then worked with author Dr. Haddad to work up the final copy,' Mitchell said in the e- mail. Eric Litchfield, a spokesman for Cohn & Wolfe, didn’t immediately return a call seeking comment.
Peter Haddad, a researcher at Greater Manchester West Mental Health NHS Foundation Trust in the U.K., was listed as the article’s lead author. Haddad didn’t respond to requests for comment.
The global Lilly team approved a draft of Haddad’s ghost- written paper in 2000, according to the unsealed documents.
Lilly marketers, rather than articles' putative authors, sometimes exerted pressure to get ghost-written articles published. For example,
Lilly officials e-mailed journal editors to complain about delays in publishing favorable Zyprexa articles, according to the unsealed documents.
In one instance, Lilly employees contacted the Journal of Clinical Epidemiology about delays of an article criticizing a previously published piece linking Zyprexa, as well as the class of atypical antipsychotics, to diabetes.
After Suraja Roychowdhury, Lilly’s senior scientific communications coordinator, wrote to the journal in November 2002, its editor, Andre Knottnerus, replied in an e-mail that it was 'a bit strange to be contacted via the Lilly product team. Dr. Buse and coauthors can contact us directly next time.'
Knottnerus was referring to the manuscript’s lead author, John Buse, a former president of the American Diabetes Association. A copy of the Nov. 22, 2002, e-mail was included in the unsealed documents.
Patrizia Cavazzoni, a Lilly staffer who co-wrote the article, e-mailed Buse on Jan. 9, 2003, seeking permission to send a separate e-mail asking to expedite publication. She also asked Buse if he would prefer 'to send it in your name?'
It isn’t clear from the e-mail chain whether the e-mail was sent by Buse or Cavazzoni.
Finally, Lilly developed a handbook for ghost-writers:
To ensure that ghostwritten Zyprexa articles met Lilly’s standards, company officials issued a guide to preparing them, according to the unsealed files.
The guide, 'Medical Press: Pre-Launch Feature Outline,' was undated. It’s unclear from the documents which teams in Lilly’s top 10 markets for the drug received it.
The primer provided a how-to for writing articles, such as instructing the author to use Zyprexa’s generic name, olanzapine, instead of its brand moniker, according to the documents. Scientists in medical research traditionally refer to a drug’s chemical name.
The guide also offered tips on how to find authors by identifying a 'key opinion leader' and providing them either an outline of the article or a finished copy. Authors could include a study investigator, an advisory board member or “Lilly-friendly” doctor, according to the documents.
A sample article laid out how a Lilly employee may find a doctor to ghostwrite a submission that would 'prepare the market' for the launch of an intramuscular injectable version of the drug. It also offered an outline for the contents of the article, beginning with background on another drug, droperidol, which had been withdrawn from several countries.
The article, with the suggested title 'Filling the Droperidol Gap,' noted that an anti-anxiety drug could be used, before going on to say, 'more advanced IM treatments may soon be available to provide a superior alternative.' The article explained that injectable Zyprexa had just received approval from the FDA, and recounted its clinical trial history.
'The anticipated forthcoming availability of atypical antipsychotics in an IM formulation could be a major step forward in the treatment of acute agitation associated with schizophrenia,' the sample article concluded.
We addressed ghost-writing frequently when we started Health Care Renewal, and have returned to the topic periodically (see these more recent links, from 2008, here and here). The most striking feature of this newest case is the use of a "ghost-writers' handbook" denoting how systematized the practice has become. With each new case, it becomes clearer how common the practice may be. Since the parties involved seem ashamed enough of the practice to try to keep it well hidden, it may be that ghost-writing is even more common than we now realize.
Nonetheless, while the practice may be common, and mutually advantageous for ghost-writers, the academics who front for them, and the marketers who hire them all, as we and others have said before, ghost-writing is dangerous to health. It deludes physicians and patients into thinking health care products are more beneficial and less risky than they really are. Ghost-writing also undermines science by shifting the agenda away from interesting and important questions to questions whose answers may mainly benefit vested interests. Finally, on a personal note, ghost-writing demoralizes honest academics who must run their own studies, write their own papers, and manage the logistics of paper submission in competition with fake authors backed by corporate money and corporate staff. Scientists and academics who allow and front for ghost-writers ought to be ashamed of themselves.
See also comments in the Clinical Psychology and Psychiatry blog, and discussion of some of the other recent revelations about Zyprexa marketing in the Hooked: Ethics, Medicine and Pharma blog.
ADDENDUM (14 June, 2009) - Also see comments by Prof Margaret Soltan on the University Diary blog on the "Stockholm Syndrome" as manifested by "key opinion leaders" in the pay of health care corporations.
ADDENDUM (15 June, 2009) - Furthermore, see comments by Dr Howard Brody in the Hooked: Ethics, Medicine and Pharma Blog.