June 28, 2011 - By Ruthann Richter
Eugene Carragee and colleagues have discovered that a product widely used in spine fusion surgery causes serious side effects. The findings raise questions about why these harms had not been mentioned in earlier studies, whose authors had received money from the maker of the surgical product.
Orthopedist Eugene Carragee, MD, has stepped into the eye of the storm in a new controversy over a bioengineered protein commonly used in spinal fusion surgery.
Carragee, editor-in-chief of The Spine Journal and professor of orthopedic surgery at Stanford, is leading a bold move by the journal to examine how researchers who received millions of dollars from the maker of the protein — the giant medical device maker Medtronic Inc. — did not report serious side effects, such as male sterility, in early published studies.
While Carragee isn’t looking to get embroiled in the fight, which could involve the Justice Department and Congressional hearings, he seems unfazed by the prospect. After all, he’s treated refugees in Cambodia, served with the U.S. Special Operations Forces in Korea and the Balkans and been wounded in Iraq.
“It won’t be like the road from the Green Zone to the airport,” he said, referring to the bomb-littered route in Basra, Iraq.
Carragee, 57, a one-time boxer and stevedore, said he began to notice reports of complications with Infuse, Medtronic’s name for the bioengineered protein product, in the medical literature in 2006. After he became the journal editor three years ago, he also began receiving many letters from orthopedists and others who reported problems with the treatment.
“My colleagues and I were starting to get letters saying, this doesn’t add up,” he said. “The sponsored studies kept saying they saw no complications at all, yet the non-company studies showed a lot of complications.”
A year ago, the editors of the journal decided to investigate. They systematically reviewed the original FDA data, as well as the spine literature, and found the risk of complications to be at least 10 to 50 times greater than previously reported in industry-sponsored studies. These complications include male sterility, urinary problems, infection, nerve and bone injury and possible cancer risk. Some authors of the early studies, who reported virtually no adverse side effects, received at a minimum between $1 and $23 million annually from Medtronic, the review found.
“If there weren’t millions of dollars riding on it, this would be a dry discussion on the appropriate use of statistics and methodology,” Carragee said. “The problem is in the last 10 years, between $3 billion and $5 billion has been spent on this product, and it’s not clear what benefit has been achieved compared with how many patients have been harmed by it. The industry estimate of harm is simply wrong.”
The review appears in the June 29 online publication of The Spine Journal, which is devoted entirely to the subject and includes an editorial by Carragee and colleagues. [The contents are outlined in a release and in a summary of the review from the journal as well as in another story by the medical school's communications office]. A separate study by Carragee was published online in the journal June 1.
Medtronic has released a statement from its CEO saying the journal’s review did not raise questions about the company data supplied to the FDA or about product labeling and saying it will continue to investigate questions regarding researchers’ potential conflicts of interest.
It’s not the first time Carragee has challenged the status quo in spine surgery: in 2006, he published a paper suggesting that many patients do better without certain lumbar surgeries, given time.
A graduate of Stanford medical school, Carragee directs the orthopedic spine service at Stanford, which he started in 1990. He has won numerous outstanding research awards for his work, including the development of a new assessment method for herniated discs and research in disc testing and spine instability.
A soft-spoken, unassuming man, Carragee said that he has taken up this latest fight because he feels a strong sense of obligation to patients. The son of a warehouse worker, he lost his mother and two siblings in the same year to cancer. He was just 10 years old.
“As a 10-year-old, you don’t understand the medicine, but you understand the empathy or lack of it. It’s pretty easy to tell who cares and who doesn’t,” he said. So as a physician today, “I feel a fundamental obligation to do it right.”
Raised on New York City’s Lower East Side, Carragee said he initially wasn’t much of a student in college, but he was a serious Catholic and decided to take time out from his education to volunteer with Catholic Relief Services in Vietnam in 1975, helping evacuees at the end of the war. It turned his life around.
He would later become involved in treating Vietnamese boat people who were flooding into Hong Kong, working with both the U.N. High Commissioner for Refugees and the U.S. Army. In 1992, while helping evacuate and treat Cambodian refugees with the U.S. Army, he was injured in an artillery explosion that fractured his hip; he calls it his “Forrest Gump” wound of war.
In 1998, he was transferred to become the Command Surgeon for a reserve unit of the U.S. Army Special Operations Forces, providing medical and strategic support around the world. He took a leave of absence from Stanford to do two tours of duty in Iraq in 2005 and 2007. During his second stint, he was seriously injured in an explosion in Diyala Province — including a chest injury, a dislocated shoulder and burns — and spent a year recovering. He does not like to talk about his military experience (some of which involved classified material), saying only that war and combat are terrible experiences especially for the young soldiers and Marines in forward areas.
“There are people performing great acts of valor. I wasn’t one of them,” he said.
But Alan Garber, MD, PhD, a former Stanford classmate who is about to leave the Stanford medical school faculty to become Harvard University’s next provost, said that Carragee is a humble guy. Garber called him “a genuine hero.”
“Here’s someone with a family and a great career, and he still takes the time to serve his country and puts himself in danger doing it,” said Garber. “He has tremendous integrity. Gene knows a lot and he never claims to know something he doesn’t. That’s why you can always be sure that when he says, ‘This is the case,’ you can believe him.”
Carragee said the most gratifying thing he does today is treat patients, and he’s troubled by the idea that some may have been unwittingly harmed by the use of Infuse, which consists of recombinant bone morphogenetic protein (rhBMP-2). In a recent retrospective study of 242 patients at Stanford treated with the protein, he found the risk of male sterility was between 6.7 and 7.2 percent. Early studies had indicated the risk was less than 1 percent. Carragee’s study, published earlier this month, suggested far fewer men would have opted for the procedure had they known the true risks.
“It’s not that the product shouldn’t be available for people who need it, but people should understand there are complications,” he said.
Charles Rosen, MD, clinical professor of orthopedic surgery at UC-Irvine, said that in bringing the issue to light, Carragee is “doing a really courageous thing, as he’s saving thousands of men from this fate.
“He is going against the tide of big industry in medicine and influential highly paid consultants for the sake of the public,” added Rosen, president of the Association for Medical Ethics. “He is sticking his neck out but he is doing it for the right reasons — for the integrity of the spine field and for the sake of patients.”
Carragee said he is just doing his job.
“This should be the bread and butter of what clinical publications do, which is critically evaluate the evidence and create a dialogue about the advantages and disadvantages of treatment,” he said. “It only appears courageous because some others haven’t done it.”
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