Industry-sponsored research that paid millions of dollars for some physicians touting a bone growth product used in spinal fusion surgery has left other doctors flabbergasted. Their diagnosis: trouble.
Eugene J. Carragee, MD, editor-in-chief of The Spine Journal was one of those flummoxed by the resultant studies that he and his co-editors vehemently assert failed to mention potential problems with the product.
As Carragee notes, spine care involves a small circle of physicians. He's had dinner with some of the physicians he is now sharply criticizing and has attended conferences with them. The circle is now broken.
"This is not a big community," Carragee told HealthLeaders Media. "I know all of them by sight, and probably [have]had dinner with them. They are charming people, great dinner companions, with a lot of energy and good surgical skills, but that's not what we are talking about here."
Carragee, who won a Purple Heart for his military service in Iraq, acknowledges he's not one to shy away from controversy. He's now involved in one that's not going to go away soon.
An orthopedic surgeon with the Stanford University School of Medicine, Carragee and a team of experts wrote a scathing analysis last month in The Spine Journal debunking reports written by physicians who made millions of dollars from a device manufacturer that found no complications with its bone growth product.
The Spine Journal is the scientific, peer review journal of the North American Spine Society, comprised of more than 6,200 members.
While the physician reviewers found no problems with Medtronic's Infuse product, The Spine Journal team said it uncovered plenty, characterizing the other physicians' reports as misleading and biased. Medtronic, the nation's largest maker of medical devices, is being scrutinized over promoting Infuse, a bioengineered material used mostly in spinal fusions. The company estimates that Infuse is used in about one quarter of the more than 400,000 spinal fusions performed in the U.S. annually.
Specifically, The Spine Journal report contradicts early industry-sponsored clinical research on rhBMP-2, a controversial synthetic bone growth product often used in spine fusion surgeries. That research reported no adverse or complications involving hundreds of patients over 10 years.
But The Spine Journal, in a series of reports comprising the June issue, asserts that the use of rhBMP-2 has been associated with various early inflammatory reactions, cancer, infections, implant dislodgement, and occasionally life-threatening complications. The dispute underscores what Carragee says is the search for "transparency" in a tangled web of money and potential conflicts involving physicians and device manufacturers, with patient care in the balance. Those issues are at the core of multiple federal investigations into what the five physician authors wrote in The Spine Journal as "biased and corrupted research" that reflect special interests and are potentially harmful to patients.
Meanwhile, the physicians who have been criticized by Carragee and his team have denounced the The Spine Journal reports, blasting them as inaccurate. An official of Medtronic did not respond to a HealthLeaders Media request for comment, but the company's chairman and CEO, Omar Ishrak, issued a statement that "integrity and patient safety are my highest priorities," according to The New York Times.
Recently, there have been a back-and-forth series of letters – and attacks – that is nothing short of astounding. These aren't politicians. These are physicians. The media has described The Spine Journal's across-the-bow commentaries as unprecedented, but Carragee says he and his colleagues are just doing what they have to do. He has an easygoing demeanor and laughs a lot. He wants to right what he perceives as wrongs.
Carragee says The Spine Journal anticipates publishing more reports on clinical trials in an effort to improve "transparency in medical reviews published in journals that he says is long overdue.
A few years ago, Medtronic received approval to use Infuse for bone growth use in what Carragee called a "narrow indication" from the Food and Drug Administration. Since then, "there has been an explosion of use off-label," Carragee says. "There weren't complications listed in multiple papers from the industry. That was a red flag; that was not credible," he adds.
"By 2009, we started looking at it. We certainly weren't the only people thinking something pretty weird was going on," Carragee says.
The Senate Finance Committee has begun investigating whether Medtronic's large payments to physicians played a role in the lack of reporting complications. Senate Finance Committee chairman Sen. Max Baucus, (D-MT), and senior committee member Rep. Chuck Grassley, (R-IA), have asked the medical device manufacturer to "produce documents related to its controversial bone growth product Infuse," the committee stated. The committee raised concerns in a letter sent to Medronic "over recent media reports that indicate medical researchers in charge of Infuse clinical trials may have been area of and failed to report evidence that the product may cause sterility in men and potentially-harmful growth." The letter notes "many of these investigators had substantial ties to the device manufacturer."
The product, officially called Infuse Bone Graft, represents about $700 million in annual sales for Medtronic. The Justice Department opened an inquiry into the off-label use of Infuse in 2008, according to The Wall Street Journal. Carragee says he's given the Senate Finance Committee "some documents ahead of (publication)," adding, "There are a lot of papers in the pipeline."
Investigators and the media are scrutinizing physician relationships with Medtronic, The Wall Street Journal further reported. Over the past decade, 15 surgeons have collectively received $62 million from the medical device company, for unrelated work, based on an analysis of Medtronic documents and financial disclosures.
Thomas Zdeblick, director of the University of Wisconsin-Madison Spine Center and professor and chairman of the Department of Orthopedics & Rehabilitation in Madison, is one of the physicians who allegedly wrote studies supporting Infuse without characterizing its potential detrimental impacts, according to The Spine Journal. He did not respond to a HealthLeaders Media e-mail.
In a response letter to the publication, Zdeblick wrote that The Spine Journal's criticisms were "Inappropriate and irresponsible."
"Although interesting, a single publication in the medical literature does not constitute a 'truth," Zdeblick wrote.
Referring to Carragee's overseas stint in the military, he described his "18-month" hiatus as impacting his style as a surgeon. "I am concerned not only with the validity of the conclusions drawn but also with the tone of the commentary chosen to accompany the article," Zdeblick added.
Carragee and his colleagues responded to Zdeblick in a letter, writing that the physician made "unwarranted personal and professional attacks."
''The old saying is 'follow the money' and in this case, there is plenty to follow," Carragee and his co-authors wrote. Carragee wrote that Zdeblick had a "$23 million financial relationship" with Medtronic that has been the "subject of a publicly documented investigation by Sen. Charles Grassley (R-IA)." Zdeblick also receives "millions of royalty dollars" from a tapered fusion device product sold separate from the Infuse Bone Graft, but must be used together with the product, they wrote.
"If a guy has done good work and discovered great things and gets royalties for it, he should get paid for whatever the market bears," Carragee says. "The question is: should he be writing the basic seminal paper on it as well. Or maybe he should be writing a white paper for the company."
"I think we have to separate advertising copy from scientific articles," he adds. "If you want to write advertising copy, plenty of people will have a section for it."
Carragee criticized the lack of proper procedures in documenting disclosures and other areas that could reveal potential conflicts of interest. The Spine Journal also is changing its disclosure requirements for its top staff, he says.
The journal has taken steps to restructure its editorial process ensuring divestiture and disclosure of potential conflicts.
"If we want people to be transparent, we ought to be transparent," he says.
Joe Cantlupe is a senior editor with HealthLeaders Media Online.
