Medtronic ($MDT) has given Yale University a $2.5 million grant to independently review the safety and effectiveness of its recombinant bone morphogenic protein-2 product, which stimulates bone formation.
The product, which is known as Infuse, has several side effects, including male sterility. However, company-sponsored researchers have been accused of attributing that complication to surgical technique, not the product. But now members of Congress and the academia are looking into how product's risks were downplayed in certain scientific articles.
The device giant will give Yale all available patient-level data on rhBMP-2 from clinical trials it sponsored--both published and unpublished--as well as all FDA-filed adverse event reports to execute a comprehensive review of the entire body of evidence, according to a Medtronic release. Yale will commission two clinical research organizations specializing in systematic reviews to conduct the analyses and ensure the findings are "reproducible and of the highest integrity."
Medtronic will voluntarily make all of its clinical trial data on the product available on ClinicalTrials.gov. It also will retroactively register all premarket approval and post-market studies that were completed before the September 2007 requirement for registering such trials was established.
Yale School of Medicine's Harlan Krumholz also will assemble a steering committee of 12 to 15 advisors. The company says it will not participate in the selection of the research organizations or the steering committee, the reviews or the manner of the data release. Yale will seek to complete the reviews within 6 months and plans to make the data available within 18 months.
"Integrity and patient safety are Medtronic's highest priorities, so it is important that a respected academic institution provide a publicly trusted source of information by way of these systematic reviews and the novel data access program for researchers," Omar Ishrak, chairman and CEO of Medtronic, explains in a statement. "In recent years Medtronic has put in place several voluntary, industry-leading policies on conflicts of interest and appropriate research practices. Our continued leadership in the area of business ethics is one of my top personal priorities, and I'm committed to continuous improvement and the consideration of new and improved policies as warranted," he added.
In a separate statement, Eugene Carragee, editor-in-chief of The Spine Journal, says Medtronic's move appears to be a big first step in the right direction. Back in June, the journal published a series of articles alleging that side effects of Infuse were downplayed or omitted in scientific articles by researchers with financial ties to the devicemaker.
However, he adds, there still remains three major challenges for true transparency and patient safety:
- The inability of the Yale researchers to fix the study design flaws and assessment biases that were used in some of the original studies;
- Because the original Medtronic-sponsored articles did not report any rhBMP-2 adverse events, the voluntary reporting of FDA-recognized adverse events by surgeons was hampered because neither they nor the patients recognized that many of the complications were rhBMP-2-related in the first place; and
- The top use of rhBMP-2 now is posterior lumbar interbody fusions; however, a randomized trial for this particular use was never halted early on because of complications and adverse events. As a result, the Yale group will have very little controlled data to judge actual safety of the product.
Back in June, one of the authors in The Spine Journal said the spine care field is at "a precarious intersection of professionalism, morality and public safety." As to whether Yale's move will improve this situation, Carragee told FierceMedicalDevices in an email that it's too early to tell. "There are multiple forces at work here, including the Senate Finance Committee investigations, the DOJ investigations and Grand Jury process, an increased scrutiny on the part of the journals themselves and now the Yale group's review. I think it will be hard to [get] back to business as usual but there remain powerful forces of inertia and resistance to change."
That said, Carragee has had what he called a productive discussion with Dr. Krumholz. "He is very enthusiastic about providing a new model for independent clinical studies assessment and we are 100% behind him in that effort," Carragee told FMD. "He and I plan to continue our dialog and we plan to meet at some point soon to share ideas."
He also said industry could improve transparency by funding a registry of off-label use and complications, as there is currently good data for only two indications of BMP-2 use available. "[T]he other 90+% of use in the U.S. is a complete black box," he explained.
- see Medtronic's statement
- check out the release from The Spine Journal