Medtronic, the world’s largest medical device maker, hit the motherlode with a bioengineered bone growth protein widely used since 2002 in spinal fusion surgery. Known as INFUSE® Bone Graft, it’s a genetically engineered version of a protein that’s naturally released by the body and used during surgery to stimulate bone growth – for example, in order to strengthen the lower spine by fusing two adjacent vertebrae together.
But Medtronic forgot to mention that many of its favourable studies published about INFUSE had been drafted and edited by its own employees (including marketing department staff, in a practice called medical ghostwriting) while 13 physicians claiming to be the study authors had been paid $210 million by Medtronic over a 15-year period, according to a U.S. Senate investigation.
Senator Max Baucus, D-Mont, explained:
“Medtronic’s actions violate the trust patients have in their medical care. Medical journal articles should convey an accurate picture of the risks and benefits of drugs and medical devices, but patients are at serious risk when companies distort the facts the way Medtronic has.”
INFUSE was FDA-approved for limited use in the lumbar spine (lower back) and for some oral/dental procedures. Specifically, the agency approved INFUSE Bone Graft to treat degenerative disc disease and open fractures on the tibia. It was marketed and sold as one of the alternatives to the painful harvest of a bone graft from the patient’s hip.
INFUSE is not approved for any other uses, but it has nevertheless been used off-label by some surgeons in cervical spine (neck) procedures (despite reported serious problems associated with cervical procedures including difficulty breathing, swallowing or speaking, compression of the airway, respiratory depression, nerve damage, or death).
Those very favourable studies published in peer-reviewed medical journals initially depicted INFUSE as a major breakthrough in back surgery. These rave reviews helped turn the product into a profitable revenue star. Medtronic generated $3.4 billion in sales from its spinal unit in the 2011 fiscal year, of which about $800 million came from INFUSE.
But many of these favourable Medtronic-funded studies were ultimately accused of overstating the benefits of INFUSE (even during approved uses) while removing or downplaying concerns about serious complications including male sterility, infection and increased back/leg pain.
The investigation by the U.S. Senate Committee on Finance was prompted in part by Journal Sentinel/MedPage Today joint investigations that showed how “the practice of medicine has been corrupted by conflicts of interest involving doctors, drug and device companies and medical journals.”
These media investigations also reported:
“Highly positive studies published in peer-reviewed medical journals depicted Medtronic’s spine fusion product as a major breakthrough in back surgery, but those studies were drafted and edited with direct input from company employees, while the doctors listed as authors were paid millions, according to a U.S. Senate investigation.”
Not surprisingly, Medtronic said it disagrees with many of the findings in the Senate report, claiming in a news release:
“The vast majority of the ($210 million) payments were royalty payments made to compensate physicians for their intellectual property rights and contributions, not consulting payments. In general, royalty and consulting payments are a commonplace and appropriate practice in the medical device industry.”
The individual payments to the 13 surgeons were substantial, by anybody’s definition. According to The Journal Sentinel‘s John Fauber:
“Financial ties between University of Wisconsin orthopedic surgeon Thomas Zdeblick and Medtronic date back to 1996 and include more than $34 million in consulting and royalty payments, according to documents from a U.S. Senate investigation.
“The payments to Zdeblick were the most for any individual among the $210 million paid over 15 years from 1996 to 2010 by Medtronic to a group of surgeons who wrote favorable medical journal articles about the company’s spine surgery product, INFUSE.
“In addition, Zdeblick received an additional $1.5 million in 2011 and 2012, according to Medtronic’s website.”
Among the 5,000 documents turned over by Medtronic to Senate investigators was a 2001 PowerPoint presentation by Zdeblick that he delivered to other doctors. These slides indicate that he knew that the sterility complication rates in a clinical trial of INFUSE were higher in men who got the product (up to 10.3%) than those in the control group (1.5%). Zdeblick noted that the 10.3% rate was “statistically different” from the control group rate. An estimated 50,000 men undergo INFUSE procedures each year in North America.
But here’s where the story gets just a wee bit slimy. When Journal Sentinel staff emailed him last year asking whether he had made a mistake by not telling doctors who had read his papers about this complication, Zdeblick’s response was:
“Wrong! In my experience there is no direct link between INFUSE and (the complication).”
A later statement from the University of Wisconsin then claimed that Zdeblick had “no recollection of presenting such data.”
Both of Zdeblick’s papers were published in the Journal of Spinal Disorders & Techniques, where Zdeblick coincidentally has been editor-in-chief since 2002.
This is extremely handy when you can be both the author of a paper you want to get published, and a medical journal’s editor-in-chief who gets a say in picking papers to publish!
His journal role was also the subject of a 2009 Journal Sentinel investigation that found this journal frequently published favourable articles about Medtronic products under Zdeblick’s watch. The story noted that Zdeblick’s financial relationship with Medtronic was not disclosed by the journal.
In addition to reports of INFUSE adverse effects, a June 2011 issue of The Spine Journal indicated a number of problems with the process in which INFUSE had been approved by the FDA in the first place. The Spine Journal pointed to a variety of financial conflicts of interests, for example, between the doctors reporting to the FDA that may have not been disclosed.
Dr. Eugene Carragee, chief of spinal surgery at Stanford School of Medicine in Palo Alto, California, also served as editor of The Spine Journal, which published an unprecedented issue that repudiated the papers written about INFUSE by doctors with known financial ties to Medtronic. Dr. Carragee later wrote:
“We do not have an accurate assessment of safety in 85-90% of the people receiving this product. Obviously, this remains a big problem.”
The Spine Journal’s editorial decision to focus on this one single issue was so unusual that it attracted widespread attention, such as this reaction from former New England Journal of Medicine editor, Dr. Marcia Angell, who told MedPageToday:
“This is really extraordinary. I’ve never seen a journal publish an issue devoted to debunking a popular treatment, and, by implication, the authors of the studies that promote the treatment.”
Several doctors who had been involved in these Medtronic-sponsored studies defended their reports, telling The New York Times that their studies were “scientifically sound and free of company influence, either directly or indirectly”.
One of them – quelle surprise! – was Zdeblick, who told The Times that he did not have a “direct financial interest in the success of INFUSE or Medtronic.”
Last year, Stanford researchers published a study of their own patients that found strong evidence that INFUSE is indeed linked to the sterility complication. As reported in The New York Times:
“That finding is in stark contrast to earlier research by doctors paid by Medtronic, who found no connection between the product INFUSE and a condition that causes sterility.”
In an e-mail to the Times, Zdeblick dismissed Dr. Carragee’s Stanford study as being “of limited value” because it reflected the results of a retrospective look at patients rather than a clinical trial. Such reports “are notorious for being misleading,” he wrote.
Total payments from Medtronic to the individual doctors highlighted in the Senate investigation ranged from about $3 million to the $34 million paid to Zdeblick. A Kentucky corporation associated with two of the 13 doctors also received $64.8 million from Medtronic between 1996 and 2010.
Finally, Medtronic’s PR machine gets the last few words in their statement:
“Medtronic has worked diligently over many years to lead the industry in reforms designed to eliminate or mitigate potential conflicts of interest, including disclosure of payments to physicians.”
Allow me to offer here the benefit of my 30+ year background in corporate, government and non-profit public relations in order to translate that PR-speak into plain English for you:
“Blah blah blah . . . “
UPDATE, May 7, 2014: Medtronic to spend $140 million to settle Infuse spinal fusion lawsuits.
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