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Senate Committee Report Says Medtronic Manipulated Studies


A 16-month US Senate Committee on Finance investigation into Medtronic, the maker of InFuse, a recombinant bone morphogenic protein-2 (rhBMP-2) product used in spinal fusion surgery, has found "questionable ties" between that company and physician consultants who tested and reviewed its products.
In a report released yesterday, the Finance Committee, which has sole jurisdiction over Medicare and Medicaid, determined that without public disclosure of their roles, Medtronic employees collaborated with physician authors to edit, and in some cases, write, segments of published studies on rhBMP-2. The studies as published may have inaccurately represented the product's risks and may have placed added weight on adverse effects of alternative treatments, according to a press release issued by the Committee.
Medtronic also maintained significant, previously undisclosed financial ties with physicians who authored studies about the product, making $210 million in payments to physicians during a 15-year period, the Committee concluded.
"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," said Senate Finance Committee chair Max Baucus (D-Mont.) in the statement. "Patients everywhere will be better served by a more open, honest system without this kind of collusion."
Specifically, the investigation concluded that:
  • "Medtronic was involved in drafting, editing, and shaping the content of medical journal articles authored by its physician consultants who received significant amounts of money through royalties and consulting fees from Medtronic. The company's significant role in authoring or substantively editing these articles was not disclosed in the published articles. Medical journals should ensure any industry role in drafting articles or contributions to authors be fully disclosed.
  • Medtronic paid a total of approximately $210 million to physician authors of Medtronic-sponsored studies from November 1996 through December 2010 for consulting, royalty, and other arrangements.
  • An email exchange shows that a Medtronic employee recommended against publishing a complete list of adverse events, or side effects, possibly associated with InFuse in a 2005 Journal of Bone and Joint Surgery article.
  • Medtronic officials inserted language into studies that promoted InFuse as a better technique than an alternative by emphasizing the pain associated with the alternative.
  • Documents indicate that Medtronic prepared one expert's remarks to the FDA [US Food and Drug Administration] advisory panel meeting prior to InFuse being approved. At the time, the expert was a private physician but was later hired to be a vice president at Medtronic in 2007."
"These findings emphasize the value of the Grassley-Kohl Physician Payments Sunshine Act, which will result in public disclosure of industry payments to physicians starting next year," Chuck Grassley (R-Iowa) said in the statement.
"The findings also should prompt medical journals to take a very proactive approach to accounting for the content of the articles along with the authorship of the articles and studies they feature," he added. "These publications are prestigious and influential, and their standing rests on rigorous science and objectivity. It's in the interest of these journals to take action, and the public will benefit from more transparency and accountability on their part."
Medtronic Response
In its own statement, Medtronic points out that it cooperated with the Finance Committee inquiry, providing documents as requested and addressing questions raised by the Committee staff. It also said it has always considered "patient safety and integrity its highest priorities."
The company notes it does not agree with many of the findings in the staff report. "In particular, Medtronic vigorously disagrees with any suggestion that the company improperly influenced or authored any of the peer-reviewed published manuscripts discussed in the report, or that Medtronic intended to under-report adverse events," the company said in the statement.
The report's characterization of payments received by physicians is also "misleading and unfair," the Medtronic statement asserts. "The vast majority of such 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."
Medtronic said it agrees with many of the recommendations in the Senate staff report to ensure increased transparency for industry interactions with physicians and maintains it has played a leadership role in this area.
Serious Complications
The FDA approved rhBMP-2 in 2002 for use in anterior lumbar fusion surgery on skeletally mature patients, excluding pregnant women, but it has been applied widely off-label. In 2008, after receiving reports of serious complications — including concern that the product may cause sterility and potentially harmful bone growth — the FDA warned that the off-label use of rhBMP-2 in cervical fusion procedures was unsafe. However, the product continued to be widely used; Medtronic's estimate is that it has been used in more than 500,000 patients, the Senate Committee's statement notes.
Additional questions about rhBMP-2 surfaced in June of last year with a series of review articles that appeared in The Spine Journalreported at that time by Medscape Medical News. One of the articles, by Eugene Carragee, MD, editor in chief of the journal and chief of the Spine Surgery Division at Stanford University Medical School in California, and colleagues, charged that several harmful effects of Medtronic's product went unreported in the published articles supporting its safety and efficacy.
Clinical trial data submitted to the FDA made it clear that rhBMP-2 was associated with a significant number of adverse events, The Spine Journal review pointed out, yet none of the 13 published industry-sponsored studies reflected these results.
"The Medtronic-sponsored studies failed to report even 1 single adverse event of any type," Dr. Carragee toldMedscape Medical News at the time. "And the FDA data are completely different. The FDA data show there was increased radiculitis, an increased number of leg pain events, increased infection rates, and an increased chance of sterility. It's astounding. But it was completely under the radar initially."
In a statement about the new Senate Committee on Finance report, Michael Heggeness, MD, PhD, and Charles A. Mick, MD, from the North American Spine Society (NASS) acknowledged the committee "for its in-depth investigation into physician/industry relationships, scientific publishing and the marketing of a Medtronic product often used in spinal fusion surgery," rh-BMP2.
"While the report confirms what was reported in the June 2011 issue of The Spine Journal, the committee's access to Medtronic's internal documents presents a more detailed and disturbing picture of what can go wrong when ethics and patient safety are compromised for profit," Dr. Heggeness and Dr. Mick write in the statement.
"Annually, millions of health care professionals make important health decisions with their patients based on the data published in scientific journals, presented at medical conferences and shared by colleagues and sales representatives," they write. "To protect the safety and health of all patients, NASS strongly advocates that this data be accurate, complete and that any potential conflict of interest that might result in bias is disclosed. NASS is hopeful that future research sponsored by Medtronic and others will adhere to much higher standards."

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