The U.S. Senate Finance Committee released a report on Oct. 25 claiming the company edited studies by outside researchers about Infuse, inserting claims that the product was superior to other treatment options. The report concludes a 16-month investigation covering 5,000 documents relating to 13 studies of Infuse.
“The company’s significant role in authoring or substantively editing these articles was not disclosed in the published articles. Medical journals should ensure industry role contributions be fully disclosed,” the committee’s report stated.
Sen. Chuck Grassley (R-Iowa), a senior member of the finance committee, said in a 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. These publications are prestigious and influential, and their standing rests on rigorous science and objectivity.”
He added that the Grassley-Kohl Physician Payments Sunshine Act would start mandating public disclosure of industry payments to physicians next year.
Medtronic has been embroiled for the past few years in ongoing investigations into off-label use of its Infuse product.
The Senate Finance Committee launched an investigation in the summer of 2011 after reports surfaced that physicians with financial ties to Medtronic failed to reveal adverse reactions in company-sponsored research papers about clinical trials between 2000 and 2009. The U.S. Department of Justice had launched an investigation as well, which inconclusively closed in May. In April, Medtronic agreed to pay $85 million to settle a shareholder lawsuit originally brought against the company by the Minneapolis Firefighters’ Relief Association in December 2008.
The lawsuit, which was consolidated into a class action in 2009, claimed the Minneapolis, Minn.-based company was deliberately misleading about Infuse. Medtronic was accused of withholding that as much as 85 percent of Infuse sales depended on “off-label” uses, which means that sales representatives allegedly were promoting the product for uses not approved by the U.S Food and Drug Administration (FDA). Some of the doctors who used Infuse, according to the lawsuit, were paid by Medtronic.
The Senate inquiry was spurred, in part, by the release last year of a special issue of a medical publication, The Spine Journal, a publication of the North American Spine Society (NASS), which held its annual meeting in Dallas, Texas, in late October. In that report, a group of spine specialists publicly rejected the studies performed by the Medtronic-financed researchers, claiming they had understated serious adverse effects connected with Infuse, including increased risk of cancer, infections, bone dissolution, worsened back and leg pain, and male sterility.
The Spine Journal reported at the time that 13 Medtronic-sponsored studies related to Infuse had reported no adverse events, but that, in fact, the rate of adverse events ranged from 10-50 percent. The researchers involved defended the reports as accurate. Senate investigators reviewed internal Medtronic documents and reported that the company paid about $210 million from 1996 to 2010 in consulting fees, royalties and other payments to doctors involved in outside research of Infuse.
Medtronic officials vehemently deny that its employees improperly influenced or wrote any of the medical journal reports. Officials also claim the studies accurately represent the procedure’s risks and that payments to researchers mostly were royalty fees that were in line with industry practice.
“Medtronic does not agree with many of the findings in the staff report,” according to a statement released by the company. “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. In fact, Medtronic reported to the FDA the potential adverse events addressed in the staff report, and these risks were reflected on the product’s FDA-approved label. In addition, the staff report’s characterization of payments received by physicians is also misleading and unfair. 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.”
The Senate inquiry found that internal Medtronic documents indicated the company had put language into reports claiming that Infuse was superior to alternate treatments such as bone grafts because it eliminated the pain associated with harvesting bone from a patient’s pelvis. The report also charges Medtronic with pressuring study authors to make a "bigger deal" of the pain experienced by patients who chose a treatment other than Infuse. In one case, the report alleges, a Medtronic employee recommended that details on the adverse effects of Infuse not be published in a 2005 article in the Journal of Bone and Joint Surgery. Those details ultimately were not included in the piece.
“Medtronic agrees with many of the recommendations in the staff report to ensure increased transparency for industry interactions with physicians, and indeed has played a leadership role in this area,” the company’s statement continued. “Scientific and engineering collaboration between physicians and industry is vital to innovation and advancing patient care. In the context of publications and consistent with best practices, physician authors interact with Medtronic employees who have scientific or clinical backgrounds and deep expertise in data related to our products because this collaboration is important to patient care. Medtronic has worked diligently over many years to lead the industry in reforms designed to eliminate or mitigate potential conflicts of interest, including disclosure of payments to physicians. Medtronic was one of the first companies to voluntarily disclose payments to physicians on a public website, more than a year ahead of new federal disclosure requirements under the Affordable Care Act.”
Last year, after publication of The Spine Journal issue, Medtronic gave a $2.5 million grant to Yale University researchers to conduct an independent review of all Infuse studies to determine the facts.
That review is ongoing.
“Patients everywhere will be better served by a more open, honest system without this kind of collusion,” the chairman of the Senate Finance Committee, Max Baucus (D-Mont.), said in a statement.
“Medtronic’s actions violate the trust patients have in their medical care. 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.”
Infuse was approved in 2002. According to Medtronic, Infuse has been used to treat more than 500,000 patients and generated sales of about $800 million in fiscal 2011. The FDA declined to approve a higher-strength version of Infuse called Amplify due to concerns that it causes cancer.
A Swift Industry Response
Michael Heggeness, M.D., Ph.D., and Charles A. Mick, M.D., outgoing and incoming presidents, respectively, of NASS, were quick in their response to the committee’s findings.
“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,” Heggeness and Mick wrote. “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. 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.”
Heggeness and Mick questioned that If surgeons had known that the lead authors of the 13 original studies on Infuse had received payments ranging from $1.7 to $64 million from Medtronic and that its marketing employees were co-authors and co-editors, would they have been as eager to use Infuse on their patients?
They noted that The Spine Journal requires all authors to provide detailed financial information about their relationships with industry, which is provided to the reader accompanying each article.
FDA Calls for ‘Spying’ Case to be Thrown Out
In July, The Wall Street Journal reported that documents had leaked revealing to the public an apparent case of the U.S. Food and Drug Administration (FDA) sanctioning spying on employees it found to be dissident. Now, the agency has asked a federal judge to dismiss the case brought against it by six current and former employees who claim they were targeted due to pointing out problems with FDA practices. These employees told lawmakers the FDA was improperly approving cancer screening medical devices.
Termed “whistle-blowers,” the employees first must make claims of “alleged whistle-blower retaliation,” FDA’s counsel said in a filing with the United States District Court of the District of Columbia. Those claims then must be reviewed through an administrative process before the plaintiffs seek judicial action. The agency said five of the plaintiffs have complaints pending before the U.S. Office of Special Counsel, which handles government whistle-blower allegations.
The FDA’s complaint, according to the filing, is that there simply are too many people making a complaint at once, and it is not being handled correctly:
“Unlike most such cases . . . this action involves not a single federal employee (or former employee) complaining of personnel actions taken against him or her because of alleged whistleblowing, but rather six individuals complaining of various personnel actions. This unwieldy, hydra-headed action illustrates why a claim of whistleblower retaliation is supposed to be brought by ‘an employee.’”
The agency also claims that the plaintiffs are incorrectly bypassing the congressionally mandated procedure for bringing claims to court according to the Civil Service Reform Act of 1978. “Plaintiffs are seeking both administrative and judicial relief simultaneously. Plaintiffs’ attempt at a procedural shotgun blast must fail,” W. Scott Simpson, a lawyer for the U.S. Department of Justice, said in the filing.
According to the filing, the monitoring began more than three years ago, after nine FDA employees signed a letter to President Barack Obama’s transition team alleging government misconduct in the approval of medical devices, including an imaging device used to diagnose breast cancer. The “spying” allegedly was expanded in 2010 after The New York Times published an article in which FDA scientists criticized the device approval process.
The lead plaintiff in the case is Paul Hardy, a former officer of the U.S. Public Health Service Commissioned Corps. The other plaintiffs are three former FDA scientists, Ewa Czerska, Robert Smith and Julian Nicholas, and two current FDA employees, R. Lakshmi Vishnuvajjala and Nancy Wersto.
The case is called Hardy v. Shuren, 11-01739, U.S. District Court, District of Columbia (Washington).