Feb. 9, 2016
Using Medical Journal Articles to Approve High-Risk Devices Is Dangerous, Misguided
Proposal Is Moving Through Congress; Public Citizen Report Outlines Bias and Conflict of Interest in Journal Reports
WASHINGTON, D.C. – Relying solely on medical journal articles when reviewing new, high-risk medical devices – a practice that would likely become more common under a proposal gaining traction in Congress – is dangerous and shortsighted, a Public Citizen report released today shows.
Even in the most respected journals, the peer-review process can permit fraudulent or inaccurate articles to be published, Public Citizen shows.
The journal article proposal was contained in a little-discussed provision in the 21st Century Cures Act, passed last summer by the U.S. House of Representatives. Although the U.S. Food and Drug Administration (FDA), under its broad discretionary authority, approves a very small percentage of devices based on information in peer-reviewed articles, the House proposal would pressure the agency to engage in this unsound practice more often.
At 10 a.m. today, the U.S. Senate Committee on Health, Education, Labor and Pensions begins marking up bills purportedly aimed at advancing medical innovation in the United States. While the proposal to rely on peer-reviewed journals is not in the bills under consideration, it could come up in future Senate bills.
Public Citizen’s report, “A Risky Shortcut,” shows the folly of relying on journals to approve devices. Retractions of peer-reviewed biomedical research articles, in some cases due to allegations of fraud, have steadily increased in recent decades. One study cited in the report found a roughly 10-fold increase in retractions since 1975.
“Peer-reviewed journals are essential to the accumulation of scientific knowledge, but they lack the requisite resources, public oversight and assurance of safeguards to be relied upon for final decisions,” said Dr. Michael Carome, director of Public Citizen’s Health Research Group. “At their worst, journal articles, often written by authors with conflicts of interest, can serve as breeding grounds for biased and inaccurate medical data.”
For instance, Medtronic’s Infuse Bone Graft device was designed to facilitate spinal fusion by using a protein to spur bone growth. The product, approved in 2002, was billed as being so revolutionary that it could replace traditional spinal fusion treatment, which involves harvesting bone from elsewhere in the patient’s body to be implanted into the spine.
Numerous industry-funded, peer-reviewed studies lauded the product and found it safe. “INFUSE Bone graft may now become the new gold standard,” one article speculated. Bolstered by these rave reviews, it was being used for about 25 percent of spinal fusions within four years of its approval.
But serious questions emerged over the product’s safety and the accuracy of studies that reached such rosy conclusions. A review in a leading spine journal published in 2011 looked at complications and adverse events reported in FDA documents and subsequent publications, and concluded that risks posed by the product were “10 to 50 times the original estimates calculated from industry-sponsored publications.”
The U.S. Senate Committee on Finance concluded in 2012 that “Medtronic was heavily involved in drafting, editing, and shaping the content of medical journal articles authored by its physician consultants” and had encouraged these authors to omit side effects. The committee also reported that the authors of the articles received $210 million from the company for royalties, consultation and other services. Thomas A. Zdeblick, the product’s inventor, co-authored two of the earliest favorable articles and was editor of the Journal of Spinal Disorders & Techniques, in which those articles were published. Zdeblick received $34.2 million from Medtronic.
A second example in Public Citizen’s report concerns CardioMEMS, a paperclip-sized wireless device implanted in patients at risk of heart failure. The device is designed to permit physicians to monitor patients’ blood pressure remotely, thereby guiding physicians in making treatment decisions.
A study published in the prestigious British journal The Lancet reported that fewer patients who used the product were hospitalized. A co-principal investigator of the study called this finding a “grand slam home run.” An accompanying commentary billed the product as presaging a “revolution in patient monitoring.”
But the FDA discovered problems in the way the study was conducted that may have biased the results and made it impossible to know whether the device was truly effective. The agency therefore did not initially approve the device.
Although CardioMEMs was eventually approved over the objections of Public Citizen, the approval was delayed for three years after the FDA’s discovery of flaws in the study purporting to show its effectiveness. The FDA’s inquiry made public crucial details to the medical community that were not disclosed in the version of the study published in The Lancet.
“The FDA’s oversight of medical devices is already notoriously weak,” said Lisa Gilbert, director of Public Citizen’s Congress Watch division. “Encouraging the FDA to limit its fact-finding to often industry-funded journal articles would create a fast track to the market for even more dangerous and ineffective devices, and bad decisions likely would result.”