Medtronic shareholders charged that Medtronic “failed to reveal that as much as 85.2 percent of Infuse sales depended on so-called ‘off-label’ uses,” and that after the company revealed that it was under investigation by both the U.S. Department of Justice as well as the U.S. Senate, share prices fell dramatically.

Dr. Zdeblick has maintained strong financial ties to Medtronic since 2003, receiving royalty payments ranging from $1.7 million to $4.6 million per year. During this time period, Dr. Zdeblick published several positive research papers on Medtronic spine products, including a 2003 study on a new Medtronic spinal product that wrote in “unusually glowing language” that the product could “become ‘the new gold standard’ in spine surgery.”

Medtronic and the University of Wisconsin, however, stated to the Journal Sentinel that Dr. Zdeblick does not receive royalty income for any Medtronic spinal implants used by University of Wisconsin Hospital doctors. 

In 2009, the U.S. Senate Finance Committee investigated financial relationships between doctors and medical device companies. At the time, Dr. Zdeblick had already earned $19 million in royalties from Medtronic.

The Journal Sentinel added:

Zdeblick long has been at the center of a swirling debate about Medtronic and its controversial back surgery product, Infuse – and the influence of money in medicine.

The fact Medtronic products invented by Zdeblick are implanted in patients at UW Hospital was revealed in 2009, in response to an inquiry by the U.S. Senate Finance Committee, which was investigating payments to doctors by medical companies.

In the letter to U.S. Senate investigators, university officials acknowledged Zdeblick had implanted four kinds of Medtronic devices that he invented or had a role in inventing a total of 179 times in the previous three years.

The most implanted device (89 times) was the LT-Cage. It is used in spinal fusion surgery and was part of clinical trial that helped gain U.S. Food and Drug Administration approval for the bone growth agent known as Infuse, or BMP-2.

Under the Act, if a medical device was approved under the expedited 510(k) process, “which now requires companies only to show their devices are smilar to those already on the market,” the FDA could require post-market studies to determine safety. The FDA could also grant partial device approval for devices approved under the 510(k) process, pending futher saftey studies.

In addition to introducing post-market safety legislation, the Senators have also sent investigative letters to five medical device manufacturers, including Medtronic, requesting information on their post-market surveillance of products.

For Medtronic, the Senators sought information specifically on the Infuse bone graft. The Senators stated:

“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…did not report negative findings from clinical trials. We are concerned that consumers, who have long relied on your products, are being adversely affected by these issues, both through the on-label and off-label use of the product.”

The Star Tribune reports, Medtronic had no specific comments on the letter other than to say, “We have received the letter and are working to comply with their request.”

The Justice Department alleged that Medtronic paid illegal kickbacks to doctors by filtering money through two post-market studies and two device registries which required each patient to have a Medtronic device implant. Medtronic allegedly “paid doctors a fee ranging from about $1,000 to $2,000 per patient” enrolled in these studies and registries. Because of the financial incentive of being able to enroll their patients in these studies and registries, physicians choosing pacemakers and defibrillators for Medicare and Medicaid beneficiaries were allegedly more likely to choose to use Medtronic medical products.

The Daily Journal reports that Benjamin Wagner, U.S. attorney for California’s Eastern District, stated, “Today’s settlement highlights one of the key purposes of the Anti-Kickback law – to ensure that judgement exercised by health care providers in treating Medicare and Medicaid patients is not influenced by unlawful payments.”

Medtronic admits no wrongdoing as part of the settlement.

The California Attorney General subpoena is the latest incident in a string of highly publicized concerns about the Infuse bone graft. In June 2011, an issue of the Spine Journal was devoted to discussing troubling evidence that some researchers were influenced by financial ties with Medtronic to downplay negative side effects of the bone graft. Known side effects include uncontrolled bone growth, cancer, and male sterility. In June 2011, concerned by these and other media reports of researchers’ financial conflict of interest, the U.S. Senate Finance Committee requested “records including communications between the company and researchers who participated in Medtronic-sponsored clinical trials as well as medical journals.”

Medtronic is also under investigation by the U.S. Department of Justice for alleged off-label marketing of Infuse, which is only approved for anterior lumbar fusion between the L5 and S1 vertebrae.

In “Financial Payments by Orthopedic Device Makers to Orthopedic Surgeons,” Dr. Jason Hockenberry of Emory University reports that in 2007, five medical device manufacturers paid orthopedic surgeons upwards of $198 million in consultancy fees, with 43 payments exceeding $1 million. According to the data analysis, these financial payments to orthopedic surgeons earning a typical salary (between $370,000 and $525,000) likely represent 25% or more of the surgeons’ income. This statistic is especially troubling “because previous studies have found that even seemingly trivial gifts, such as pens and small food purchases, from pharmaceutical sales representatives can alter physician behavior.”

Hockenberry examines data released after five orthopedic implant makers, including DePuy Orthopedics and Zimmer, settled a kickback probe with the U.S. Department of Justice in 2007 by accepting federal monitoring and agreeing to publish the names of the physicians they paid as consultants, and the amounts paid to each, on their websites.

Hockenberry concludes that the “impact of the DOJ settlement in the short term appears complex, with an increase in payments, a decline in the number of consultants, and an increase in the proportion of consultants drawn from academia.” Medical device makers may be trying to limit the total number of payments they make, instead targeting physicians in academia who “have a disproportionate effect on national orthopedic practice through professional societies and instruction of orthopedic trainees.” Hockenberry emphasizes that “there is a need for clearer specific requirements for disclosure to allow for meaningful long-term analyses.”

Engel’s experience also puts him at the intersection of two growing medical controversies – dangerous side effects from off-label use of the Infuse bone graft, and the rise of failed back surgery syndrome.

Failed Back Surgery Syndrome Defined

The International Association for the Study of Pain defines FBSS as “lumbar spinal pain of unknown origin, either persisting despite surgical intervention or appearing after surgical intervention.”

The Los Angeles Times notes in, “For back pain sufferers, surgery isn’t always the answer,” spinal surgeries in the United States are performed at double the rate of other developed nations, with no corresponding evidence that Americans are actually suffering from back pain at twice the rate of their extranational counterparts. Further, “there is a long-standing controversy among spinal specialists over how often surgery is the best option — and some say surgeons can be too quick to sharpen their scalpels.”

The St. Petersburg Times reports that about 800,000 Americans have back surgery each year, but “evidence is mounting that for many patients, surgery is no better at relieving pain” than non-surgical treatment options, and that “some patients are even worse off after surgery, leading the profession to coin the term ‘failed back surgery syndrome.’” Dr. Norman Marcus tells the Record Searchlight that “half of all patients who had a spinal fusion or laminectomy surgery say they ended up no better or worse off after the procedures.”

Why is back surgery so popular in the United States? Dr. Steven Richeimer, chief of the division of pain medicine at USC, speculates that the United States’ extraordinarily high rates of spinal surgery may be cultural – he states, “We’re in a little bit of a quick-fix society.”

Medical Device Industry Payments for Research: Example of Medtronic’s Infuse Device

Another possible reason for the rising popularity of spine surgeries is the financial entanglements of doctors with medical device companies. Some doctors who recommend surgery over other treatment options, or who promote the use of specific medical devices used in spine surgery, have received enormous amounts of money from spine device companies. In many case, these doctors failed to disclose their financial ties to the medical device companies.

Certain physicians who published early studies on the Infuse bone graft system manufactured by Medtronic earned millions of dollars in consulting payments from Medtronic. For example, the Milwaukee Journal Sentinel reported that surgeon Thomas Zdeblick received more than $22 million in royalties and other payments from Medtronic since 2002.

The early industry-sponsored studies on BMP-2 (the bone growth protein in Infuse) either failed to disclose or dramatically downplayed the side effects of BMP-2, including ectopic bone growth, unusual inflammatory cysts, osteolysis (or bone resorption) causing cage migration following spine fusion surgeries.

The nonprofit Foundation for Informed Medical Decision Making strives to help patients research treatment options and make fully informed decisions regarding surgery. Another resource for patients is the Association for Medical Ethics, founded by Charles Rosen, M.D., director of the Spine Center at UC Irvine. Dr. Rosen founded the Association for Medical Ethics (AME) in 2006 out of his concern over the rise in surgery rates. The AME calls for transparency from doctors who receive over $50,000 in consulting fees from medical device companies.

Earlier this year, Dr. Rosen sharply criticized the “marketing-disguised-as-research” that can arise from industry-sponsored research. Dr. Rosen cited Medtronic-sponsored research on the Infuse bone graft as an example of the harm that patients can suffer when new medical devices are brought to the market based on research conducted by physicians that are paid by the device manufacturers.

Dr. Rosen observes that some pharmaceutical and medical device manufacturers are willing “to sweep these problems (complications) under the rug and influence their researchers, sometimes with millions of dollars, to do the same.”

Dr. Rosen cited Medtronic’s Infuse bone graft device and early research that revealed no complications from the use of bone morphogenetic protein (BMP), the bone graft material contained within Infuse:

It is regrettable, but appears to be the case, that many of the researchers who may have had the opportunity to review the primary data strongly suggesting multiple BMP-2 complications were heavily conflicted by large financial associations with the corporate sponsor [Medtronic]. There is a suspicion that some of these surgeon-researchers had abandoned the appropriate sense of responsibility for their fellow human beings when lured by the almighty dollar.

No one is saying that the industry should not fund clinical studies or hire clinical consultants to promote products they believe in, but the arrangement must be transparent and the industry must report how much to be helpful to the readers.

Recent studies have reported temporary as well as permanent male sterility in patients who have been implanted with the Infuse bone graft.  Patients have also filed Infuse lawsuits against Medtronic for uncontrolled bone growth.

English charges that Infuse caused her to develop ectopic, or uncontrolled, bone growth in her spine, compressing nerves and leading to chronic and ongoing severe pain.

Compelled to undergo two revision surgeries so far to remove the excessive bone growth, including an emergency surgery, English suffers continuous pain in her back and legs from ordinary everyday activities, such as sitting or standing for extended periods of time. “I trusted Medtronic with my life,” stated English. “It is disappointing to find out Medtronic is not looking out for the best interests of the patient, but for own its financial interests.”

English’s attorney, Lieff Cabraser attorney Wendy Fleishman, stated, “When Infuse is implanted in off-label surgeries, medical research shows that it can cause uncontrolled bone growth into or around the spinal cord, often leading to intractable pain and difficult and dangerous revision surgeries to remove unwanted bone.”

John Lane of O’Fallon, Missouri, had Infuse injected into his neck in a surgery that his surgeon allegedly promised would relieve his chronic pain. Instead, “bone spurs formed in Lane’s neck and new bone was pushing on his spinal cord,” and the pain “became indescribable and unrelenting.” Lane commented, “If they were going to use me as an experiment or a guinea pig, I would have liked to have had options and the facts.”