Since 2002, the medical device company Medtronic and a group of doctors with financial ties to the company were aware that its new biological agent used in back surgery was linked to a serious complication: sterility in men.
But that information was not revealed in published manuscripts written by those doctors, a group that included orthopedic surgeons who would receive millions of dollars in various royalties from the company, a Milwaukee Journal Sentinel/MedPage Today investigation found.
Now, prompted in part by earlier Journal Sentinel/MedPage Today articles, independent researchers at Stanford University conducted a retrospective review of outcomes of patients treated at Stanford and published the findings today in The Spine Journal. The Stanford team found that in their patients use of recombinant human bone morphogenetic protein-2, or BMP-2 -- marketed as Infuse by Medtronic -- was associated with a measurable rate of retrograde ejaculation, a condition that causes sterility.
Read this story on www.medpagetoday.com.
Indeed, in the main arm of the clinical trial that led to the approval of BMP-2—data that were submitted to the FDA in 2002—five of 78 men treated with BMP-2 developed the retrograde ejaculation compared with one of 68 men who received the standard hip bone graft, according FDA records.
In another arm of the clinical trial, an additional six of 57 men (10.5 percent) treated with BMP-2 also developed retrograde ejaculation.
Yet, as recently as last year the BMP-2 investigators with financial ties to Medtronic claimed there was "no relationship" between the product and the complication.
And the doctors' denials fly in the face of a Medtronic statement included in a 16-page document obtained by the Journal Sentinel/MedPage Today from publicly available FDA files. In that document company states that retrograde ejaculation is a potential adverse event that may occur with Infuse.
And when contacted by the Journal Sentinel/MedPage Today Medtronic and the doctors contended the sterility complication was caused by surgical technique, not the product, which they said was why the sterility data were not included in the published papers
But professional guidelines and independent doctors contacted by the Journal Sentinel/MedPage Today say serious complications should be listed in published papers, regardless of what is believed to be the cause.
A new Journal Sentinel/MedPage Today analysis found that last year alone Medtronic paid more than $6 million in royalties for various products to the physicians who co-authored the BMP-2 studies, but the company and the authors note that none of those royalties were for Infuse.
One of the authors, Dr. Thomas A. Zdeblick, is a University of Wisconsin School of Medicine and Public Health orthopedic surgeon who, along with Taz Consulting, has received more than $23 million in various royalty payments from Medtronic since 2002. Zdeblick also is the editor of the journal that published two of the papers that failed to mention the link.
In an email, a spokesperson for the Univeristy of Wisconsin said that Zdeblick "neither owns equity in Medtronic nor receives royalties or any other payments for the sale of Infuse, either now in the past."
A previous Journal Sentinel/MedPage Today investigation found that doctors who had financial relationships with Medtronic reported substantially better results using BMP-2 in clinical trials leading to its approval than did doctors who reported no financial ties to the company.