Infuse is safe to use, says Medtronic CEO

54

In response to The Spine Journal’s decision to dedicate a whole issue to a heavily critical review of Medtronic’s recombinant human bone morphogenetic protein-2 (rhBMP-2, Infuse Bone Graft), the company’s chairman and chief executive officer Omar Ishrak said that the product was safe to use. “We strongly believe that the safety profile reported to the FDA and summarised in the product label support the safe use of rhBMP-2 for the identified indications.”

In the journal, Carragee et al estimate that the rate of adverse events associated with the use of the device in spinal fusion ranges from 10 to 50% depending on the approach. They claim that with rhBMP-2, compared with controls, there is a 40% greater risk of adverse events in the early postoperative period, including life-threatening events after anterior cervical fusion; there is higher incidence of implant displacement, subsidence, infection, urogenital events, and retrograde ejaculation after anterior interbody lumber fusion;  posterior lumbar interbody fusion use is associated with radiculitis, ectopic bone formation, osteolysis, and poorer global outcomes; and that the risk of adverse events in posterolateral fusions is equivalent to or greater than that of iliac crest bone graft harvesting.

 

Additionally, Carragee et al write that the original studies on rhBMP-2 underestimate its risk of adverse events. “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 dedicated issue is an editorial in which Carragee et al say that a potential “intrinsic confounding factor” in the original studies was the fact that some of the authors had “tens of millions of dollars of financial associations” with Medtronic. They add that the association between favourable outcomes in spinal implant research and industry funding is not unique, quoting Gelberman et al who reported that the “complex financial relationships” between orthopaedic surgeons and the medical device industry are associated with a “threat to scientific integrity and public trust.”

 

Carragee et al’s criticisms are not just levelled at Medtronic and the authors of the original papers. They are also critical of peer-review journals that publish industry-sponsored trials “disclosures in our journals [referring to orthopaediac journals as a whole] are more often than not self-contradictory blurbs of improbable nonsequitors bracketed by misdisrection.” They report that an article on rhBMP-2, published in Spine in 2007, stated that no benefit had been or would be directly or indirectly received for the mention of rhBMP-2 in the study, and claim that “even the most cursory review” showed the authors had a substantial amount of financial associations with the sponsors of the article (ie, Medtronic). “If the disclosure lacks ‘minimal credibility’, what does this say about the study’s content?”

 

According to Carragee et al, the spinal world is now in a precarious position in which there is a burden of suspicion that new technology research and publication is simply “a broken system” and that change is needed. The Spine Journal, therefore, has said it will describe a number of editorial, procedural, and disclosure-related changes that it hopes will “achieve a better balance in critical manuscript review, conflict of interest disclosure, and publication presentation” in upcoming issues. It adds “we must all do a better job going forward.”

 

In his statement, Omar Ishrak only briefly refers to the original papers criticised in the journal.  He says that although the journal criticises these papers, it does not raise questions about the data submitted to the FDA in the approval process or the information available to physicians today through the instructions-for-use brochure. He says that these data are the reasons why Medtronic believes rhBMP-2 is safe to use.

 

“We remain committed to the ongoing study of the safety and efficacy of rhBMP-2, especially in applications not covered by FDA labelling.” He added that “integrity and patient safety” were his highest priorities. “For several years, Medtronic has been leading the industry in reforms designed to eliminate or mitigate conflicts of interest. We will continue to investigate questions surrounding researchers’ potential conflict of interest, refine our policies as warranted and strive the lead industry in ethical and transparent business practices.”