Two long-awaited independent reviews of a controversial Medtronic Inc bone growth product show it works as well as traditional bone grafts taken from patients, but it may not be as safe.
The analyses, published on Monday in the Annals of Internal Medicine, suggest that Medtronic's Infuse product was associated with a small, increased risk of cancer, and that early published data on the trials underreported side effects and emphasized favorable results.
Writing in an editorial in the same journal, doctors said the Medtronic product should be reserved for certain, select patients, and that the costs and risks of the product should be clearly spelled out.
The reviews were prompted by questions raised by spine experts and U.S. lawmakers about the safety of the Infuse product, which contains a genetically-engineered protein used to promote bone growth known as recombinant human bone morphogenetic protein 2.
Infuse was once hailed as a major advance in spine surgery by offering a way to ease the pain of spinal fusion surgeries, in which bones in the neck or spine are fused together. Traditionally, a portion of bone known as a graft is harvested from other parts of the body to encourage bone healing. Infuse was developed to promote bone healing without the need for painful bone harvesting.
But in 2011, Infuse became the subject of investigations by the U.S. Senate and the Department of Justice over omissions of safety problems from its clinical trial data and over off-label use.
The product also drew intense public scrutiny after the influential Spine Journal ran an entire issue criticizing the product in June 2011, charging that surgeons, who were paid tens of millions of dollars by Medtronic, failed to report serious complications, such as male sterility, increased risk of cancer, infections, bone dissolution and worsened back and leg pain.
To address these questions, Medtronic in 2011 agreed to two independent reviews of its trial data. As part of the Yale University Open Data Access project - spearheaded by Dr. Harlan Krumholz - teams of researchers at Oregon Health & Science University in Portland and Britain's University of York, were selected to conduct the reviews.
The Oregon team found that in spinal fusion, the Medtronic product worked no better than bone harvested from a patient's own body.
In trials, Infuse was compared to iliac crest bone graft, which involves taking bone from the rim of the pelvic bone, which can lead to complications such as pain or infection.
The Oregon review also found that Infuse was associated with an increased risk of cancer after two years, although the overall risk was low and did not involve a particular type of malignancy. They also found that published trial data emphasized the positive, while underreporting side effects.
The University of York researchers found that after two years, Infuse offered no clinically important pain reduction and was associated with a possible increased risk of cancer, although again, the overall risk was low.
The findings suggest that Infuse should be used primarily as an alternative for patients who otherwise would require more than one incision to harvest their own bone for grafting at the surgery site, according to an editorial by Dr Daniel Resnick of the University of Wisconsin and Dr Kevin Bozic of the University of California, San Francisco.
They said patients should be counseled on the relative benefits and harms, as well as the costs of each graft option.
Medtronic had a somewhat more positive take on the conclusions of the reviews.
"The findings reinforced what we know about the product in the sense that the studies concluded equivalence, and in some cases superiority, to iliac crest bone harvesting," said Chris O'Connell, president of Medtronic's Restorative Therapies Group. "It's really up to the physician to interpret the data."
He said Medtronic views its cooperation with the Infuse reviews as part of a bigger industry trend toward open access to medical trial data.
The company said it has funded an analysis of real-world usage of Infuse to gauge its association with cancer risk and expects those results to be presented at a medical meeting in the fall.
The U.S. Food and Drug Administration approved Infuse in 2002 to stimulate spinal bone growth in patients with a degenerative disease affecting the lower spine.
In March 2012, Medtronic agreed to pay $85 million to settle a shareholder lawsuit accusing it of failing to reveal that as much as 85.2 percent of Infuse sales depended on so-called "off-label" uses, where doctors prescribe the product for applications not approved by the FDA.
The product had sales of $528 million in fiscal 2013, far below the $800 million the company reported in fiscal 2011.
(Reporting By Deena Beasley; Editing by Julie Steenhuysen, Bernard Orr)