Senators Question Medtronic on Infuse Side Effects

Three U.S. Senators have written to Medtronic Inc., seeking information about the way the company monitors the performance of medical devices once they come to market. According to a report from Minneapolis Star Tribune, the Senators expressed special interest about side effects associated with Medtronic’s controversial Infuse bone growth product.

The letter was written by Senators Charles Grassley, R-Iowa, Herb Kohl, D-Wis., and Richard Blumenthal, D-Conn.

“A researcher at Stanford University School of Medicine found a higher risk of cancer associated with Infuse, and there have been allegations that researchers who received funds from Medtronic, sometimes millions of dollars, did not report negative findings from clinical trials,” the letter states.

Medtronic’s Infuse bone graft is made from a genetically engineered material called rhBMP-2 (recombinant human Bone Morphogenetic Protein-2), which stimulates bone growth. Infuse was approved by the U.S. Food and Drug Administration (FDA) for use in one type of spine surgery called anterior approach lumbar fusion. Later, it was approved for use in two types of dental surgeries. However, it’s long been recognized that Infuse is frequently used in procedures not approved by the FDA. In 2008, the agency warned that Infuse and similar rhBMP-2 products had caused serious problems when they were used off-label in cervical spine (neck) surgeries

The Stanford researcher referred to in the Senators’ letter is Dr. Eugene Carragee, editor of The Spine Journal. Over the summer, he published an article in the journal asserting that Medtronic-paid surgeons had failed to report serious complications from Infuse, including cancer, sterility in men, infections, bone dissolution and worsened back and leg pain. The article said complications occurred in 10 to 50 percent of patients who got the product in 13 Medtronic-funded clinical trials between 2000 and 2010. Carragee’s review also examined payment data from Medtronic to doctors who co-authored the Infuse studies, and found that, the median amount to the company paid to doctors was at least $12 million to $16 million per study (though it should be noted that none of the royalty payments related to Infuse.)

Then, just last month, Carragee again made news when he presented a study at the North American Spine Society that raised serious questions about a possible association between Infuse and an increased risk of cancer. Carragee’s analysis of a Medtronic study for its Amplify product, a higher-dose version of rhBMP-2, found that the study failed to identify a significant cancer risk though both the research team and Medtronic were aware of data linking the product to cancer. The findings have important implications for Infuse, as doctors often administer Infuse off-label at levels significantly above the recommended dosages, ones that approach or exceed the amount of rhBMP-2 found in a dose of Amplify, when they use Infuse in off-label procedures.

Their letter to Medtronic was one of five the Senators sent to medical device makers concerning their post-marketing tracking of device complications, the Star Tribune said. As we reported last week, the same group of Senators has introduced a bill that would require medical device companies to track side effects come to market for any device subject to the U.S. Food & Drug Administration’s 510(k) approval process. The FDA’s 510(k) protocols do not require that devices undergo pre-market human testing if it can be shown they are “substantially equivalent” to a product already on the market.