The experiences of one surgeon are raising questions about the costs and risks of a Medtronic Inc. (MDT) bone-growth product, threatening to pressure further the company's spinal business.
According to a study made available Wednesday by The Spine Journal, men treated with Medtronic's Infuse product were more likely to develop a certain infertility problem than those who didn't get the product during spine surgery. Editorials in the medical journal questioned why the issue wasn't examined more in Medtronic-funded studies and noted Infuse's high price tag.
The study, though, has limitations because it's based on procedures done at one hospital by one doctor, who also happens to be the medical journal's editor-in-chief. Medtronic defended its company-funded, randomized trial used to support U.S. approval by saying the rates of complication weren't high enough to create a statistical link. The company added that the issue also didn't show up in another company-backed study.
Medtronic doesn't break out Infuse sales specifically, but the product accounts for the bulk of sales in a "biologics" category that tallied $884 million in sales in the company's recently concluded fiscal year, representing nearly 6 percent of total sales. The company's spinal business is already stressed by issues like a market-wide slowdown as insurers raise hurdles to certain procedures, pricing pressure and tight competition.
Infuse, a genetically engineered version of a natural protein, is used to join vertebrae together in the lower back. It's an alternative to harvesting bone grafts from patients' hips, but there has been debate about whether Infuse use specifically raised the infertility risk compared with other treatment methods.
Eugene Carragee, a surgeon at the Stanford School of Medicine and someone who doesn't have financial ties to Medtronic, said that among the 69 men he treated with Infuse, 7.2 percent suffered from retrograde ejaculation, compared to less than 1% of the 174 patients who didn't get the product.
"In my opinion, it is important that men who are considering having children have the opportunity to weigh the risks of the various available procedures so that they can make their best-informed decision," Carragee said in a press release from the North American Spine Society, which is the association for spinal surgeons that publishes the medical journal.
The complication in question occurs when semen is redirected to the bladder rather than out the urethra because a muscle at the base of the bladder can't contract properly; this can lead to permanent infertility. It is a known complication in certain spinal-fusion procedures that is caused by damage to nearby nerves.
A corresponding editorial by Tomislav Smoljanovic and Ivan Bojanic—surgeons in Croatia—questioned why authors of the key Medtronic-backed study supporting Infuse noted cases of retrograde ejaculation but didn't break out the ones that occurred between patients treated with Infuse and patients who received bone grafts.
Another editorial questioned the benefits of Infuse while noting the product's high price tag, at $4,500 per kit.
Medtronic said it disclosed retrograde ejaculation rates by study arm to the Food and Drug Administration in its Infuse application and included the information on the product labeling.
Thomas Zdeblick, a surgeon who participated in the key Medtronic-funded study and directs theUniversity of Wisconsin Spine Center, said there was never any attempt to hide data on this issue from the original trial, but rather, there weren't enough numbers to reach statistical significance, "and the issue was left without a conclusion."
Zdeblick—who said Carragee's new study has numerous flaws—also said that while he receives Medtronic royalties regarding another spinal product that can be used with or without Infuse, he has "absolutely no financial interest" in the bone-growth product. Medtronic lists him and other surgeons involved in its key Infuse study among doctors with financial ties to the company; it wasn't making detailed financial disclosures about doctor payments when the study came out.
Medtronic said it disclosed each surgeons' financial interests based on FDA regulations, and that primary endpoint data were summarized in the regulatory submissions between the surgeons who had financial interests and those who didn't.
J. Kenneth Burkus, a spine surgeon in Georgia who also participated in the key Infuse study, said in a letter to another orthopedics journal last year that there wasn't a relationship between the Medtronic product and this infertility complication. Burkus and colleagues were responding to Smoljanovic's questions; writing in Wednesday's editorial, however, Smoljanovic and Bojanic said "this categorical denial was not credible."