What's the Real Motivation Behind Medtronic Infuse Off-Label?

Washington, DCOff-label use of Medtronic bone graft was brought to the public's attention in 2008 when the US Food and Drug Administration (FDA) warned about Medtronic infuse bone graft use in association with the cervical spine. While doctors and surgeons have always enjoyed the authority and freedom to use drugs and medical devices off-label if they think it will benefit their patients, the motivation behind some of those decisions involving Medtronic off-label has been called into question.

Infuse Bone Graft contains recombinant human Bone Morphogenetic Protein (rhBMP-2), a protein naturally released by the human body. The Infuse Bone Graft system is meant to provide surgeons and medical professionals with some level of control as to where bone can grow. Patients with degenerative bone issues or injuries can benefit from the specific placement of Medtronic Bone Graft, which serves—in lay terms—as a scaffolding over which new bone can grow, using the recombinant human Bone Morphogenetic Protein (rhBMP-2) protein.

The FDA approved the procedure specifically to treat Degenerative Disc Disease and open fractures of the tibia. The federal regulator also approved the system for use in two dental procedures, sinus augmentation and localized alveolar ridge augmentation. No other applications or uses carry the FDA seal of regulatory approval.

Two years ago this past July the FDA issued a warning after receiving 38 reports over four years with regard to off-label uses in cervical spine procedures—in other words, surgical procedures involving the neck. The reports primarily involved swelling of neck and throat tissue, which resulted in compression of the airway and other structures in the neck. Patients reported difficulty swallowing, breathing and speaking. Several required emergency treatment, including tracheotomies and the insertion of feeding tubes, as well as second surgeries.

Specifically, the complaints and adverse reactions involved unwanted bone growth in close proximity to nerves, or in areas outside the targeted surgical sites.

Recent concerns over off-label use for the regenerative bone system center on two facts. One is that the FDA had concerns over the potential for off-label use of the system even prior to approving Medtronic Infuse Bone Graft in 2002. The other is an allegation that some surgeons who used the system off-label may have financial ties to the manufacturer.

The Wall Street Journal (WSJ) obtained transcripts of a meeting between the FDA and an advisory committee called to discuss the approval of the Medtronic Infuse Bone Graft. According to the transcript, the committee asked FDA staff for recommendations for "guarding against off-label use of this product."

The WSJ, quoting from the transcript, reported the comments of Dr. Scott Boden, identified at the time as the director of the Emory University Orthopedics & Spine Center. Presenting to the committee of clinical trial data on behalf of Medtronic, Dr. Boden stated that discussion of off-label use was "outside the scope of what we ought to be focusing on today."

At the time of that statement, according to the text of a lawsuit, Medtronic was paying Boden in excess of $100,000. The Wall Street Journal reported that payments from Medtronic to the doctor continued through 2006.

In May of 2003 four surgeons authored a paper citing favorable results obtained from using the Infuse system in the neck area and fusing large numbers of vertebrae. Three of the four authors of the report had financial ties to Medtronic, according to the WSJ investigation. The alleged conflict was not revealed in the report.

Senator Charles Grassley (R-IA) looked into the matter, expressing concern that "inordinately high consulting fees, free travel and other perks distort decision-making among physicians and obscure the best interest of patients."