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Tuesday, November 8th 2011

A Critical Review of Recombinant Human Bone Morphogenetic Protein-2 Trials in Spinal Surgery

Background

  • Although the specifics of assessment and technique in fusion remain for debate spinal fusion for pain with spinal instability has become a generally accepted treatment
  • Surgery for fusion attempts to promote new boney growth between the unstable vertebral segments
  • Early last decade saw the rise in the clinical use of a naturally occurring cytokine, bone morphogenic protein-2, which serves to promote osteoblast differentiation and new bone formation in the body
  • Initial studies demonstrated great success, as compared to bone grafts alone, in promoting boney fusion between unstable segments when BMP was used during surgery
  • The Spine Journal June 2011 issue is dedicated to editorials and studies reviewing the growing evidence that BMP use has a number of risks that were underreported as adverse events in the initial studies which trumpted its use. Amongst these studies is a literature review by Carragee et al which criticizes the lack of reported adverse events in the initial industry sponsored BMP studies

Carragee, Eugene, Eric Hurwitz, and Bradley Weiner. “A Critical Review of Recombinant Human Bone Morphogenetic Protein-2 Trials in Spinal Surgery: Emerging Safety Concerns and Lessons Learned.” The Spine Journal 11 (2011): 471-91.

Design

  • Systemic review looking at adverse events reported in original 13 industry sponsored publications looking at rhBMP-2 use in spinal use representing 780 patients versus adverse events reported in subsequent publications and FDA data sets

Results

  • 13 original studies of BMP
  • All first authors had significant financial ties to Medtronic, the industry manufacturer of BMP
  • Meta-analysis of the 13 studies shows 0 complications associated with BMP
  • Review of subsequent studies, unpublished data from the original studies submitted to the FDA leads the authors to conclude that BMP has a true adverse event rate of 10-50%. Newer studies may also associate the product with a cancer risk
  • Dr. Carragee’s group proposes that the financial ties of the authors of the original 13 studies may help explain the lack of reported complications with BMP

Conclusion
Spine surgery is facing a real scandal with BMP. The association with cancer and the implication that financial considerations influenced the studies which led to its approval as a device by the FDA and to its widespread use is a big enough story that it has crept out of the pages of Spine and into the mainstream media. Reuters, the AP have both reported on it, as have major papers like the San Francisco Chronicle and the New York Times and the Wall Street Journal.

Infuse and other BMP based products are likely rightly dead and recalls are in the future. As for what this plays into the long going debate about the association between researchers and industry remains to be seen. But this is a big deal.

I’m going to be less than reactionary here. I think severing the ties between academic medicine and industry is impossible without hurting the common good. This country is the leader in advancing medical science partly because of funding from industry. I think the oversight is going to have to come from the academic institutions themselves. That’s a tough thing and there are major obstacles to people policing their colleagues. I’m not sure exactly what form that might take. But certainly I don’t think the government is not in a position to police it all. And the alternative is severing all ties to industry funded research.

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