Health News Review

In the second part of their 3-part guest blog series on ghostwriting of medical papers, researchers Jonathan Leo, PhD, and Jeffrey Lacasse, PhD address “Medtronics, InFuse and the University of Wisconsin.”

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InFuse, manufactured by Medtronic and approved by the FDA in 2002, is used for promoting the growth of bone graft material during surgery.  In 2008, the FDA issued a public health notification because some patients who had received InFuse went on to develop life-threatening swelling in their necks and throats. In 2011, Dr. Eugene Carragee reported that the patients in a clinical trial of InFuse experienced a higher number of side effects, such as retrograde ejaculation and the development of certain cancers, compared to controls.  But most problematic, Dr. Carragee suggested that a 2009 industry sponsored publication did not report this accurately.  These revelations led to several articles by John Fauber of the Milwaukee Journal Sentinel that raised several problematic aspects of the InFuse trials and conflicts of interest.  There were numerous problems documented. The most shocking one was that from 1996 to 2010, Dr. Thomas Zdeblick, one of the lead investigators and a professor of surgery at the University of Wisconsin, had been paid $34 million dollars in consulting fees.  The total for all thirteen doctors and two corporate entities involved with the studies was $210 million. This eventually led to Senator Charles Grassley and the Committee on Finance investigating the trials.

Following a sixteen-month investigation, the committee, comprised of twenty-four senators, issued a nineteen-page report – the appendix consisted of over two thousand pages.  Besides the ghostwriting charges, there were numerous charges about undeclared conflicts, underreported adverse effects and overstated efficacy, a lack of oversight by journals and universities, and the involvement of the marketing department with the papers.  In their words, “Medtronic was heavily involved in drafting, editing, and shaping the content of medical journal articles authored by its physician consultants who received significant amounts of money through royalties and consulting fees from Medtronic.”  The report also lists the papers involved and how much money was paid to the clinicians for their consulting work. For anyone who wants an introduction to the conflicts of interest in medicine the report is an eye-opener.

Not surprisingly, after the Committee report was published, Medtronic declared that the papers in question were not ghostwritten. In their words: “Medtronic vigorously disagrees with any suggestion that the company improperly influenced or authored any of the peer-reviewed published manuscripts discussed in the report.” In addition to Medtronic, the Dean at the University of Wisconsin Medical School also defended the papers: “Neither Dr. Zdeblick nor UW approves of ‘ghostwriting in any scientific circles.” The Journal Sentinel also reported that: “An emailed statement from Robert Golden, dean of the medical school, said Zdeblick has no knowledge of any ghostwriting by Medtronic on any of the papers.” At the time the Dean made these comment he also said he had not seen the Senate report.

This presented an interesting situation for anyone wanting to determine if the papers were really ghostwritten. Who was correct, the Senate Finance Committee or the paper’s defenders? To answer this, there is only one question that needs to be answered. Did the internal company documents show that there were there individuals who made significant contributions to the papers who were not listed on the bylines?

In 2004, a paper about InFuse published in the Journal Spine concluded that: “this review of the results, which represents the first use of osteoinductive proteins in a PLIF procedure, are encouraging.” On page 15 of the Senate Report there is a discussion about a January 10, 2003, e-mail to Dr. Burkus (a named author) from Rick Treharne, a Medtronic executive, stating, “I added a few paragraphs at the end that you may not agree with.”  His proposed addition starts with, “In conclusion, this detailed, independent review of the results…” His additions were incorporated into the final published paper. Regardless of his conclusions, and whether or not they are accurate, shouldn’t someone who writes the major concluding points of a paper, be considered an author?  After the paper was first submitted to the journal, the initial peer reviewers raised some objections about the paper’s bias. Treharne and another Medtronic executive then drafted a letter addressing these concerns which was submitted to the journal by one of the named authors.  The letter sought to reassure the journal editor that the authors of the paper were independent. On the paper’s byline Treharne is not mentioned.  He is not thanked for his contribution in the acknowledgement section. In our eyes, and we think most of the general public’s eyes, this omission makes this a ghostwritten article.

In 2005, a paper published in the Journal of Bone and Joint Surgery reported on the clinical and radiological findings following the use of InFuse in spinal surgery.  According to the Senate report, on February 1, 2003, Dr. Burkus sent a draft to Medtronic officials asking for “final comments.” And then on March 7 of that year, Dr. Julie Bearcroft, the Director of Technology Management in Medtronics Biologics Marketing Department, emailed Dr. Burkus an updated version with her proposed changes to the draft. And then on June 16, 2004, she wrote an email to other Medtronic employees stating: “I have made significant changes to this document (some at the request of Dr. Burkus) both in format and in content.”  According to the Senate Report, Bearcroft also recommended not including a table on adverse events in the published paper. Although Dr. Bearcroft participated in drafting the study, and in her words made “significant changes” to the document, she was omitted from the byline. After reviewing this evidence it appears to us that these papers were ghostwritten.  We can only conclude that anyone who defends these papers from the ghostwriting charges is not doing so on the basis of the facts presented in the Committee’s report, but is basing their defense on a definition of ghostwriting that allows invisible authors – a non sequitur if ever there was one.

In part 3 tomorrow, we look at ghostwriting issues swirling around the psychiatric drug Paxil.

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See part 1 of the series:  When Should a Medical Paper be Considered Ghostwritten?  Three Easy Steps to Finding Ghost Authors.”

Part 3:  “Psych drug Paxil – and conclusion

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Jonathan Leo examines the biological basis of mental disorders such as ADHD, schizophrenia, and clinical depression. Rethinking ADHD: From Brain to Culture, a co-edited volume with psychiatrist Sami Timimi, was released by Palgrave Macmillan in 2009.

Jeff Lacasse has published research on barriers to evidence-based mental health practice, including articles on critical thinking in mental health, clinical treatment of children, and psychiatric medications.

Together they have published several articles on the serotonin theory of depression and ADHD. Over the past several years their articles on ghostwriting have appeared in PLoS Medicine, The Chronicle of Higher Education, and Society.

Their research has been covered in popular media outlets such as The Wall Street Journal, Scientific American, Science,The Chronicle of Higher Education, Fortune, Nature, and the Economist.

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Comments

carol posted on January 24, 2013 at 4:35 pm

It’s outrageous that Medtronic had employees ghostwrite these studies. Doctors use research to help make important, often life-changing decisions for a patient in need. Having biased studies may not be illegal, but it is certainly unethical. At least Dr. Krumholz, who is leading the Yale review of Infuse, is determined to bring transparency to this issue and eliminate industry influence from research.

http://www.publichealthwatchdog.com/medtronic-infuse-artificial-bone-graft-may-cause-cancer-male-sterility-and-other-serious-side-effects/