In an extraordinary move, a group of spine specialists are publicly repudiating the research of other experts that has backed the widespread use of a Medtronic bone growth product. In a series of reports published in a medical journal on Tuesday, the specialists called the research misleading and biased.
The repudiation, appearing in a full issue of The Spine Journal devoted to the topic, represents a watershed in the long-running debate over conflicts of interest for the sponsorship of scientific studies by makers of drugs and medical devices. It is extremely rare for researchers to publicly chastise colleagues, and editors of leading medical journals said they could not recall an instance in which a publication had dedicated an entire issue for such a singular purpose.
Medtronic, the nation’s biggest maker of medical devices, has been facing intensifying scrutiny over its promotion of Infuse, the bone growth product at the center of the controversy. The bioengineered material is used primarily in spinal fusions, a procedure in which spinal vertebrae are joined to reduce back pain.
Infuse is used in about a quarter of the estimated 432,000 spinal fusions performed in this country each year. The articles published on Tuesday charge that researchers with financial ties to Medtronic overstated Infuse’s benefits and vastly understated its risks by claiming there were none.
“It harms patients to have biased and corrupted research published,” five doctors wrote in a joint editorial that accompanied the reports. “It harms patients to have unaccountable special interests permeate medical research.”
“The spine care field is currently at a precarious intersection of professionalism, morality and public safety,” Dr. Christopher M. Bono, editor of the special edition, said in a statement. “As physicians and journal editors, we felt an obligation to present a thorough examination of this controversial issue.”
It is too early to predict how the articles will affect the financial fortunes of Medtronic, which earned an estimated $900 million from Infuse in its most recent fiscal year. But the potential consequences seem significant, and the company’s new chief executive, Omar Ishrak, decided to issue a statement in response.
Mr. Ishrak noted that the articles did not challenge the data Medtronic had submitted to the Food and Drug Administration that led to Infuse’s approval in 2002 for use in one type of spinal fusion. Separately, other company officials said Medtronic planned to retain independent experts to examine the issues raised by the publication.
“Integrity and patient safety are my highest priorities,” Mr. Ishrak said.
Medtronic officials acknowledged in interviews that it was common for them to review studies of its products before publication. However, they sought to distance themselves from the content of the published reports, and said outside researchers, not the company, had determined the significance of data and how it should be presented. At the heart of the issue are potential side effects related to Infuse’s use that emerged during patient studies conducted about a decade ago by outside researchers with significant financial ties to Medtronic.
Medtronic, as required, reported that data to the F.D.A., and the agency considered the rate of those complications significant enough in some cases to require the company to list them on Infuse’s label. But in reporting on such studies in 13 medical journal articles published during the last decade, researchers whose studies were paid for by Medtronic maintained that Infuse’s use was not tied to any complications.
In one article released Tuesday, experts said those reports played down Infuse’s risks and slanted them to favor Infuse’s performance over a bone graft, the material traditionally used in a fusion. Those experts estimated that the incidence of adverse events in connection with Infuse’s use ranged from 10 to 50 percent, depending on how it was used.
Those side effects, they said, include male sterility, infection, bone loss and unwanted bone growth. A stronger version of Infuse, called Amplify, was recently rejected for approval by the F.D.A. because of concerns about possible cancer risks.
In 2008, the agency warned the public that it had received reports of life-threatening injuries associated with the use of Infuse in the cervical portion of the spine, a use that was not approved by the agency.
Dr. Eugene J. Carragee, editor of The Spine Journal, said he believed that Infuse was a valuable product for patients who were not candidates for a bone graft. But he added that the publication had undertaken the review because he and other experts hoped to cleanse the scientific record.
While Dr. Carragee said some researchers involved in the earlier reports were not influenced by links to Medtronic, he found it difficult to give those with major financial ties to the company such a pass. The median amount of Medtronic money received over time by researchers involved in some studies ranged from $12 million to $16 million, with most of that going to a few individuals, The Spine Journal estimated.
“A consistent number of people involved with these studies got extraordinary sums,” he said.
Both Dr. Howard C. Bauchner, editor in chief of The Journal of the American Medical Association, and Dr. Gregory D. Curfman, executive editor of The New England Journal of Medicine, said they could not think of a time when a journal had devoted an entire issue to questioning an approved product.
In recent years, medical journals and professional medical associations have adopted stronger standards requiring researchers to disclose financial conflicts of interest.
Along with Infuse’s approved use in one specific type of spinal fusion, doctors also use it in other types of spinal fusion procedures, something that they are free to do. Since 2008, however, the Justice Department has been conducting a criminal investigation to determine whether Medtronic illegally promoted Infuse for such so-called off-label uses; the company says it did not do so.
Tuesday’s articles added to an expanding number of studies pointing to serious side effects suffered by patients given Infuse. The journal also published an editorial by Dr. Charles L. Branch Jr., a Medtronic consultant, who said that the growing controversy over Infuse reflected a need to develop better ways to monitor and examine the off-label uses of medical products.
Infuse “appears to have been assigned the role of the poster child for all that is wrong with ‘off-label’ or physician-directed use of a novel beneficial technology,” wrote Dr. Branch, a neurosurgeon at the Wake Forest Baptist Medical Center in Winston-Salem, N.C.
Several researchers who were involved in the Medtronic-sponsored studies have defended their reports as scientifically sound and free of company influence, either directly or indirectly.
For example, one of them, Dr. Thomas A. Zdeblick of the University of Wisconsin, said that he did not have a “direct financial interest in the success of Infuse or Medtronic.” Over the years, Dr. Zdeblick has received over $20 million in royalty payments from Medtronic in connection with patents on devices, including one that is used with Infuse.
Dr. Carragee and his colleagues have called Dr. Zdeblick’s position “hardly credible” and “a fascinating denial of what, in our opinion, is an obvious and enormous conflict of interest.”
Asked to respond, Dr. Zdeblick reiterated his position in an e-mail, adding, “I will wait for science, not opinion, to dictate what’s really going on here.”
Dr. John K. Burkus, a surgeon in Columbus, Ga., and the lead author of four of the questioned studies, did not respond this week to e-mails and calls seeking comment. However, he has previously defended his studies and took exception last month with a report by Dr. Carragee that asserted a link between Infuse and male sterility.
Last week, two members of the Senate Finance Committee, Max Baucus, a Democrat from Montana, and Charles E. Grassley, a Republican from Iowa, sent a letter to Medtronic requesting records involving payments and communications with researchers on the Infuse studies.
