The cozy financial relationships between some of the country’s leading surgeons and Medtronic Inc. helped the Minnesota-based medical-device company gain the FDA’s approval for a spine-surgery product now associated with serious safety concerns, according to an investigative article published Sunday in the Milwaukee Journal Sentinel.
As reporter John Fauber notes, it’s a cautionary tale that is “equal parts the art of medicine and the art of the deal.” Here’s Fauber’s lede:
In January 2002, a group of Food and Drug Administration advisers met on whether to approve a powerful new biological agent that promised to revolutionize back surgery.
The product was like nothing the burgeoning field of spinal fusion surgery had seen before. If used properly, it essentially turned whatever it touched into bone. This was a good thing if it could be confined to the tiny space between vertebrae, but potentially calamitous if it leaked out.
One of the FDA advisers at the meeting raised a concern about nine of the doctors whose research on the product had been submitted to the FDA: The doctors all had a financial stake in the product, and their test results with it were nearly twice as good as the doctors who did not have a financial interest.
The concern by the FDA advisory panel member was laughed off with a joke, according to a transcript of the hearing, and the panel ultimately deferred to Medtronic, a company that stood to get billions in sales as the maker of the product known as Infuse.
What has happened since is no laughing matter.
Since recombinant bone morphogenetic protein-2, the biological agent used in Infuse, was approved by the FDA for fusion surgery, early concerns about its widespread, unapproved use and adverse reactions in patients have materialized. Studies have warned that it can cause life-threatening swelling in the neck, form bone in unwanted locations and possibly fuel the growth of cancer cells or spark adverse immune system reactions.
The approval of Infuse followed what drug industry critics say is a familiar playbook: First, a buzz is created about a potential new therapy. Then, research — often by doctors with financial ties to the product — is presented to the FDA for a specific use in a narrow group of people. Once the product is on the market, other uses for it are promoted in articles and presentations, often by doctors with financial ties to the company.
Now, Medtronic is back before the FDA, this time seeking approval for a different BMP-2 product for use in back surgery. Once again, concerns about cancer, immune reactions and effectiveness have been raised by a different panel of FDA advisers.
The story of BMP-2 raises questions about whether doctors should be allowed to do clinical trial research involving products that might enrich them or the company they work for. It also shows weaknesses in the FDA process for approving drugs and devices.
Here are few of the troubling details from Fauber’s report:
- Medtronic refused to reveal to the Journal Sentinel the names of the nine surgeons whose research on Infuse helped gain the FDA’s 2002 approval for the product. And, inexplicably, those names have been redacted from the FDA’s files. FDA officials gave the Journal Sentinel conflicting reasons for why the names are missing — and whether or not it could reproduce them from archived material. The agency agreed on Friday that it could produce the names for the Journal Sentinel — but not until December.
- The four doctors who co-authored a 2002 medical journal paper that reported on the benefits of Infuse receive royalty payments from Medtronic for various products. Their payments for the first quarter of 2010 were in the six figures each, with one prominent surgeon from the University of Wisconsin-Madison, Dr. Thomas Zdeblick, receiving $473,000.
- Of the 63 surgeons involved in the clinical trial for Medtronic’s new BMP-2 product, Amplify, 27 had a financial interest in Medtronic at the time they conducted their research. And those 27 operated on more than half of the 463 patients in the trial.
- The FDA approved Infuse only for use in spinal surgery that is approached from the front. Yet 85 percent of BMP products are used off-label, or during surgical approaches from the back. Sales of Medtronic’s Infuse have grown to about $800 million a year, much from off-label use. Companies are not allowed to market their products for off-label use, but doctors are allowed to tout off-label uses — even doctors with financial ties to the company selling the product.
Medtronic, of course, defends its product and its payments to surgeons. A spokesperson told the Journal Sentinel that (in Fauber’s words) “Medtronic is strongly committed to preventing the promotion of its products for unapproved uses and has implemented corporate policies and training to prevent that” and that “the package label for BMP-2 covers all safety concerns that the FDA believes the public should know.”
The spokesperson also added (in her own words): “Collaboration between physicians and industry remains absolutely vital to innovation in the medical industry.”
You can read Fauber’s article here. He wrote it as a joint project between the Journal Sentinel and MedPage Today. You can read his slightly more technical and physician-aimed MedPage version of the story here.