Medtronic Inc.’s Infuse Bone Graft product has been embroiled in controversy for several years now. This past year alone, several studies have called into question the safety of Infuse, and raised serious concerns about the way Medtronic Infuse side effects were reported in clinical trials for the bone graft. Unfortunately, such scandals are nothing new for Infuse. Back in 2009, a Medtronic-paid surgeon at Walter Reed Army Hospital attracted scrutiny, after the Army revealed that data he submitted for an Infuse study involving wounded soldiers had been falsified.
Medtronic Infuse Background
Infuse incorporates recombinant human bone morphogenetic protein (rhBMP-2), a synthetic recreation of a protein that is naturally available in the body. Originally, the product seemed like an innovative alternative to the traditional spinal fusion procedure, in which bone is used from the hip. When it was approved in 2002, Infuse was only cleared by the U.S. Food and Drug Administration (FDA) for use in one type of spine surgery called anterior approach lumbar fusion, and two types of dental surgeries. However, some estimates say that as many as 85% of Infuse procedures involve uses not approved by the FDA (known as off-label use). While doctors are free to use approved medical devices in anyway they see fit, it is illegal for device makers to promote those uses.
In July 2008, the FDA warned that Infuse and similar bone growth products had caused serious, sometimes life threatening complications, when used in off-label in spinal procedures. In cervical spine surgeries some Infuse patients have experienced acute severe neck swelling several days after surgery resulting in death or permanent injury. That same year, the U.S. Justice Department began investigating Medtronic’s marketing of Infuse.
The Walter Reed Debacle
In May 2009, officials with the U.S. Army revealed that Dr. Timothy Kuklo, a former Army Surgeon at Walter Reed, and paid consultant to Medtronic, had made false claims and overstated the benefits of Infuse in treating soldiers severely injured in Iraq. The data was included in a study Kuklo published in the Journal of Bone & Joint Surgery in August 2008. The disputed study claimed to show that wounded soldiers’ leg injuries healed better when Infuse was used. But according to the Army, Kuklo’s research cited higher numbers of patients and injuries than Walter Reed officials could account for. The surgeon also failed to obtain the Army’s required permission to conduct the study, and investigators at Walter Reed also concluded that Kuklo forged his co-authors signatures on the study.
In March of 2009, the Journal of Bone & Joint Surgery retracted Kuklo’s study. The scandal prompted several investigations, including one launched by Senator Charles E. Grassley of Iowa, the ranking Republican on the Senate Finance Committee. In the course of that investigation, Medtronic disclosed that paid Kuklo roughly $850,000 in direct and direct payments over a 10-year period. Between 2000 and 2006, he was paid to train other physicians in how to implant Medtronic products. In 2006, he signed on as a consultant for the company. After the accusations against Kuklo were made public, Medtronic suspended and then ended its consulting contract with him, but the company has maintained that it had nothing to do with Kuklo’s discredited Infuse research.
Recent Medtronic Infuse Controversies
Over the past year, the controversy surrounding Infuse has only grown larger. Over the summer, The Spine Journal raised serious questions about the validity of the research that was used to gain FDA approval of Infuse. One of the articles included in the journal, which that month was dedicated entirely to rhBMP-2 issues, found 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 Spine Journal 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. Medtronic Infuse injuries reported by The Spine Journal included:
- ectopic or uncontrolled bone growth at or near the site of the surgery
- ongoing or chronic radiating pain in the legs or arms
- male sterility, retrograde ejaculation, or other uro-genital injuries
- nerve injuries causing severe and chronic pain; and even cancer.
In November, Edward Carragee a prominent researcher and editor of The Spine Journal, presented a study at the annual meeting of the North American Spine Society which indicated that Infuse may be associated with a higher risk of developing cancer. Carragee’s analysis of a Medtronic study for its Amplify product, a higher-dose version of rhBMP-2, found that it had failed to identify a significant cancer risk even though both the research team and Medtronic were aware of data linking the product to cancer. While the FDA never approved Amplify, the findings have important implications for Infuse. According to Carragee, doctors often administer Infuse 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.
The controversies have taken a toll on sales of Infuse. Medtronic has since commissioned researchers at Yale University to conduct an independent review of Infuse clinical trials in an effort to salvage its reputation.