Medtronic has asked Yale University to conduct an independent review of its recombinant bone morphogenic protein-2 (rhBMP-2; Infuse bone graft) after The Spine journal dedicated its June issue to a critical review of the product.
According to Medtronic, it will provide Yale with all of its available patient-level data for rhBMP-2 (both published and unpublished) and all FDA-filed adverse event reports. It is also going make all of its clinical trial results publically available on the National Library of Medicine’s online clinical trial registry ClinicalTrials.Gov, which will include pre-market approval and post-market clinical trials that were completed before September 2007 when registering on the site became mandatory.
Rick Kuntz, Medtronic’s chief scientific officer, said, “Our pledge to support full access to the clinical data in the form of independent patient-level data for the systematic reviews, retrospective registration of trials with the National Library of Medicine, and the provision for broad investigator access of all patient-level data from Medtronic-sponsored studies, represents a novel and significant commitment to transparency and open-access scientific research.”
The June issue of Spine Journal, as previously reported in Spinal News International eBulletin, featured a review of rhBMP-2 in which Carragee et al estimated that adverse event rate associated with rhBMP-2 in spine fusion ranged from 10 to 50%, depending on the approach used and claimed that the original sponsored studies underestimated risk of adverse events with rhBMP-2. “In the small pilot studies, there was inadequate numbers [sic] to assess safety, but some suggestion of potential harms was seen in at least one study. In the larger trials, there is evidence in each trial that rhBMP-2 complications may be common and may be serious; but in each publication, these were unreported.”
However, the most damning paper in the journal was an editorial that raised questions about the reliability of industry-sponsored research. Carragee et al wrote: “Those same studies [referring to the original sponsored trials] were published by some authors with tens of millions of dollars of financial associations with the manufacturer and may have been an intrinsic cofounding factor.”
“It harms patients to have biased and corrupted research published. It harms patients to have biased and unaccountable special interests permeate medical research,” Carriage et al added.
As a result of its review, the Spine Journal has vowed to make a number of editorial, procedural, and disclosure-related changes to provide a better balance in critical manuscript review, conflict of interest disclosure and publication presentation. “We must all do a better job going forward”, Carragee et al concluded in their editorial.
Responding to the Medtronic announcement about the Yale Research Project, Eugene Carragee, editor-in-chief of The Spine Journal, said: “Without knowing the specifics of the proposed review, I can say this appears to be a big first step in the right direction.” However, he added that three “major challenges” for patient safety remained: the design and assessment biases of some of the original studies were “flawed”, which Yale University will not be able to “fix”; as the Medtronic-sponsored articles did not report any rhBMP-2 adverse events, the voluntary reporting of the FDA-recognised adverse events was “handicapped by surgeons and patients not recognising many of the complications were rhBMP-2-related in the first place”; and finally that the number one use of rhBMP-2 is in posterior lumbar interbody fusions (or its variants), but the randomised trial on this particular use was never completed. “The Spine Journal editors are pleased that our investigation into rhBMP-2 has served as a catalyst for this move by Medtronic to introduce transparency into the medical device and drug research and development process. I have been in touch with Harlan Krumholtz, the leader of this project at Yale University, and The Spine Journal would welcome the opportunity to provide input into the process as needed.”
Omar Ishrak, chief executive officer at Medtronic, said that “integrity and patient safety” were Medtronic’s highest priorities. “In recent years, Medtronic has put in place several voluntary, industry-leading policies on conflicts of interests and appropriate research practices. Our continued leadership in the area of business ethics is one of my top personal priorities.”