A U.S. Senate committee has launched an investigation into reports that doctors with financial ties to the medical device company Medtronic were aware of serious complications with a lucrative spine surgery product yet failed to reveal those problems in medical journal articles.
Citing reports in the Journal Sentinel, two leaders of the Senate Finance Committee sent a letter to Medtronic on Tuesday demanding an extensive trail of documents, including financial records and communications between the company and doctors who have received millions in royalties and other payments. Medtronic was warned not to destroy any of the documents, data or other information in the letter signed by committee chairman Max Baucus (D-Mont.) and senior member Chuck Grassley (R-Iowa).
The growing controversy involves Medtronic’s spine surgery product Infuse, which was approved by the Food and Drug Administration in 2002. Over the last year, Journal Sentinel reports have revealed large payments made to prominent surgeons around the country, including a University of Wisconsin-Madison orthopedic surgeon, who were involved in the clinical testing of Infuse or who wrote positive medical journal articles that failed to link the product to serious complications.
“We are extremely troubled by press reports suggesting that doctors conducting clinical trials examining the safety and effectiveness of Infuse on behalf of Medtronic were aware that Infuse, a treatment commonly used in spinal surgery, may cause medical complications, but failed to report this in the medical literature,” Baucus and Grassley wrote. “This issue is compounded by the fact that some clinical investigators have substantial financial ties to Medtronic.”
The letter was addressed to Omar Ishrak, who this month took over as chairman and chief executive of Minneapolis-based Medtronic.
Infuse, the brand name for bone morphogenetic protein-2, is a powerful biological agent used in spinal fusion surgery. The product stimulates bone growth and eliminates the need to harvest a small amount of a patient’s own hip bone to create a fusion between two vertebrae.
Medtronic says Infuse has been implanted in more than 500,000 patients by more than 2,300 surgeons. Its sales amount to several hundred million dollars a year.
Medtronic also is under investigation by the U.S. Department of Justice on allegations of off-label marketing of Infuse. Though doctors can use products in ways not approved by the FDA, companies are not allowed to promote them for such unapproved ways, which often have not undergone rigorous testing for safety and effectiveness. Research indicates that about 85% of Infuse use is off-label.
Sohail Mirza, a professor of orthopedics at Dartmouth Medical School, said he was pleased that the Finance Committee was investigating the matter.
“This is a sad failure of our profession,” he said. “It’s the Finance Committee doing public health work. Surgeons themselves or the FDA could have done the committee’s work earlier. Our patients would have been better served if surgeons, our professional associations, and our scientific publications had established a culture or policies that prevented this circumstance.”
In an emailed statement, Medtronic spokesperson Marybeth Thorsgaard said the company will respond the senators’ request.
She noted that three of the complications mentioned in their letter are listed as warnings on the FDA labeling for the product. Those complications involve retrograde ejaculation, which causes sterility in men; ectopic bone formation; and cervical complications such as swelling in the neck or throat.
She also said Medtronic acknowledged complications with the product to the FDA before its approval of Infuse “irrespective of any financial relationship between the company and the clinical investigator or study author.”
Responding to concerns raised by the senators about a link between Infuse and cancer, she said that in 44 clinical trials, cancer rates were not statistically different between patients who received Infuse and those who did not.
In a statement, Baucus said: “These reports that doctors conducting medical trials while on Medtronic’s payroll may have hidden serious side effects for patients are deeply troubling. We need to do everything we can to ensure companies aren’t concealing serious medical complications from patients just to increase profits.”
Patients must rely on their doctor’s knowledge of the risks and benefits of a medical device, Grassley added.
“If the medical literature has been written by those with financial ties to the device maker, the doctor and his patient should know that,” he said. “A lack of transparency leaves doctors and patients in the dark on something any of us would want to know before surgery.”
Prompted in part by Journal Sentinel reports, independent researchers at Stanford University last month found strong evidence that Infuse was linked to a complication that causes sterility in men, a connection that was not revealed in the medical literature. Their paper was published in the Spine Journal.
Eugene Carragee, lead author of that study and editor-in-chief of the Spine Journal, said his publication has received many complaints for more than a year, suggesting serious concerns about published Infuse studies. Carragee is chief of spine surgery at Stanford.
“There has been a corrosive suspicion surrounding researchers’ financial ties to Medtronic, possible company influence on data presentation and the basic safety reporting by some industry-sponsored surgeons,” he said in an email to the Journal Sentinel. “For the sake of our patients, I hope the Senate’s investigation will lay the matter to rest so doctors, patients, and their families can find out whether they can have confidence in those Medtronic studies, as reported, or not.”
Next week, independent researchers are expected to publish more papers revealing additional serious complications with Infuse that were not reported in numerous articles published over the last decade and co-authored by doctors with financial ties to Medtronic. The independent researchers said their research also was prompted in part by Journal Sentinel reports.
The Baucus/Grassley letter noted that last year the Journal Sentinel reported on a Medtronic-funded study published in 2004 that found that 75% of patients who got Infuse developed ectopic bone, a type of unwanted bone growth outside the targeted fusion area. The authors, several of whom had financial ties to Medtronic, concluded that “although not desirable” the bone formation in the spinal canal did not appear to have an ill effect on patients.
The paper was published in the Spine Journal before Carragee became editor, in 2008. In a Journal Sentinel report last year, independent doctors described the paper as more marketing than science.
Last year alone, three of that paper’s four authors received about $4 million in various royalty payments from Medtronic, the newspaper reported. None of the royalties was for Infuse.
A separate 2008 study by doctors without financial ties to Medtronic found neurological impairment from ectopic bone in five patients treated with Infuse.
Millions in royalties
The Baucus/Grassley letter also noted the male sterility complication.
Last month, the Journal Sentinel reported that since 2002, Medtronic and a group of doctors with financial ties to the company were aware that Infuse was linked to sterility in men.
But that crucial information was not revealed in medical journal articles written by those doctors, including surgeons who would receive millions of dollars in various royalties from Medtronic.
A Journal Sentinel analysis found that last year alone, Medtronic paid more than $6 million in royalties to a handful of doctors who, over the last nine years, co-authored several Infuse papers without cautioning that it was linked to male sterility. None of the royalty payments was for Infuse.
One of the authors, Thomas A. Zdeblick, is a University of Wisconsin School of Medicine and Public Health orthopedic surgeon. Zdeblick and Taz Consulting have received more than $23 million in royalty and other payments from Medtronic since 2002. Zdeblick also is the editor of the Journal of Spinal Disorders & Techniques, the medical journal where two of the Infuse papers were published.
Zdeblick did not respond to a request for comment.
“We are also concerned that other severe side effects of Infuse and similar bone-growth products developed by Medtronic may have been unreported or underreported in clinical literature,” Baucus and Grassley wrote. “Reports have linked Infuse to potentially fatal swelling in the neck and throat and radiating leg pain.”
Last year, the Journal Sentinel also found that doctors with financial ties to Medtronic produced substantially better results with Infuse in the clinical trial leading to the FDA’s approval of the product than doctors who did not have financial ties to the company.
The Baucus/Grassley letter requested a variety of records, including a detailed account of payments made by Medtronic to all of the Infuse clinical investigators.
The names of the Infuse investigators and their financial disclosures have remained redacted in FDA files since before 2002 when Infuse was approved by the agency. In May 2010, the Journal Sentinel filed a Freedom of Information Act request for the information. While the agency acknowledged that information should be public, it has failed to release it.
