Progress in medicine is essential for discovering new ways to make people healthier, experience less pain, and to live longer. The efforts of countless researchers, physicians, scientists, and patients have led to tremendous breakthroughs and progress in medicine over the past decade and without their collaboration, it would have been difficult to achieve the quality of life we enjoy today. In fact, without this process, in which drugs and medical devices are made, tested, and updated, we would never find the treatments that eventually help make our lives better.
A recent article from the Journal Sentinel however, undermines this collaboration between researchers, patients, and industry by pointing to a group of physicians involved in a powerful new biological agent that promised to revolutionize back surgery, and suggesting that financial motivations created conflicts of interest.
The drug in question, known as Infuse, “was like nothing the burgeoning field of spinal fusion surgery had seen before because it turned whatever it touched into bone.” As the Sentinel explained, the “treatment consists of a tapered, metallic fusion cage that looks like a thimble and the BMP-2 bone graft substitute. The substitute, which is placed inside the LT-Cage, includes the genetically engineered human protein (BMP-2) that is placed on an absorbable sponge. The LT-Cage maintains spacing between the vertebrae while the BMP-2 generates the formation of new bone in order to permanently stabilize that section of the spine.”
For the Sentinel, “the story of BMP-2 raised questions about whether doctors should be allowed to do clinical trial research involving products that might enrich them or the company they work for.” What the Sentinel completely ignores are questions about the positive impact BMP-2 has had on patient’s lives, and the benefits enjoyed by patients who chose this treatment over more painful options. This omission is troubling, considering the author himself admits that despite a risk of leaking out, if BMP-2 is properly “confined to the tiny space between vertebrae, it proved as an effective treatment.”
If a treatment is effective, and helps patients, then of what concern should there be about doctors enriching themselves, when patients are benefiting? Shouldn’t their hard work, dedication, investment, and the risks they are taking be adequately rewarded?
The Sentinel examines BMP-2 mainly because of the outcome of an advisory meeting panel in January 2002, which happened prior to the drugs approval. Specifically, the Food and Drug Administration (FDA) panel did not address panel member Stephen Li’s issues with the fact that nine doctors who had a financial stake in the product had test results with it that were nearly twice as good as the doctors who did not have a financial interest.
Consequently, the FDA panel deferred Li’s concerns to Medtronic, the company that was making Infuse. Explaining what happened next, Marybeth Thorsgaard, a spokeswoman for Medtronic clarified that “the company fully disclosed the success rates of the doctors with financial ties to the company to the FDA.” In fact, Markham Luke, chief medical officer in the FDA’s device evaluation office, noted that in approving the product, the FDA took into account the conflicts of interest of the investigators.
As a result, with this information in hand, the panel “probed the issue and made its recommendation to the FDA, which ultimately approved the product.” FDA also said “the package label for BMP-2 covers all safety concerns that the FDA believes the public needs to know.”
This cooperation thus showed Medtronic’s strong commitment to preventing the promotion of its products for unapproved uses and its implementation of corporate policies and training to prevent that.
Despite the commitment from Medtronic, the Sentinel believes that “the eventual approval of Infuse represented “a familiar playbook,” in which first, a buzz is created about a potential new therapy. As the Sentinel claimed, the next step is for “research – often by doctors with financial ties to the product – to be presented to the FDA for a specific use in a narrow group of people.”
The playbook then is that “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.” But nothing is illegal about these presentations or articles. In fact, the physicians who provide these service help thousands of physicians across the country learn about new treatments and therapies such as Infuse.
For example, BMP jumped from being used in less than 1% of all fusions in 2002 to being used in 25% in 2006. While the Sentinel claims that much of this increase was fueled by “off-label” use, they also correctly acknowledge that such use is “not illegal for doctors, including those with financial ties to such companies.”
It seems like the issue the Sentinel takes with the use of BMP was that there is “a considerable amount of evidence suggesting that many patients with back pain do just as well over time without” the BMP surgery. Going on this claim, they assert that “spinal fusion is a controversial treatment for degenerative disc disease,” even though they admit it is an “effective treatment.”
One would expect that for a treatment to be classified as controversial, it would have a negative success rate however, the FDA noted when approving the product that “the expected overall success for Infuse is 57.1%.” So what if fusion without using BMP-2 had a 56.7% success rate? What is the problem with having two treatments effectively treat a particular condition? Why should we be giving patients and doctor’s only one choice?
The reality is, spinal fusion surgery in the past “often required harvesting a small amount of bone from the hip, which can be painful and add time to the surgery.” When BMP was being developed, it held the potential to eliminate that pain and additional time for surgery, and still does.
What the Sentinel is really concerned about is that since the FDA approved the use of BMP for a single-level fusion involving the lumbar spine in which the operation was done from the front, “doctors have been using it off-label in surgical approaches from the back rather than the front, and on the cervical spine as well as the lumbar spine.” To support this claim, the author cites a recent study, which “found a fourfold increase in the use of all BMP products in five years, from 24,000 procedures in 2003 to 103,000 in 2007.”
Of that increase, the study asserted that “about 85% was off-label use.” But as we discussed above, it is not illegal for doctors, including those with financial ties to companies, to prescribe off-label. Accordingly, the fact that BMP has been used off-label increasingly is a positive affect because without its approval, the many uses it is now being used for would still be without effective treatment. It should be noted however, that physicians using BMP for off-label purposes should advise there patients as such.
The Sentinel also takes issue with BMP because despites its approval by FDA, “early concerns about its widespread, unapproved use and adverse reactions in patients have materialized.” The article points to “studies that 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.” But the likelihood or possibility of these risks are not discussed, and are specifically not put into the context of the benefits BMP provides.
Any surgery is going to be risky and expensive, and the fact the surgeons who are conducting these surgeries helped create, study and develop the devices and treatments through industry sponsorship is reassuring. It means that their experience and exposure to the products being used is unmatched.
New Therapy
Consequently, what brought BMP into the media was the fact that Medtronic is now back before the FDA seeking approval for a different BMP-2 product for use in back surgery. The drug, known as Amplify, was considered by an FDA panel last month, in which “concerns about cancer, immune reactions and effectiveness were raised.
Accordingly, the Amplify clinical trial, which involved 463 patients, was completed in 2009. It was noted that of 63 surgeons, twenty-seven who operated on more than half of the patients in the clinical trial had a financial interest in Medtronic at the time of the research. Despite what some feel appears to be a conflict, “Medtronic maintained that because the financially connected surgeons had results that were similar to those who did not have such conflicts, their financial interest in Amplify’s success did not affect the results of the trial.”
But the Sentinel still wants to drag Amplify under the bus by suggesting that prominent surgeons, such as Thomas Zdeblick, who helped study BMP-2, have conflicts of interest because of their financial ties to Medtronic. The fact that he holds patent rights to a key component of the product and has received more than $22 million dollars in royalties and other payments from Medtronic since 2002 does not represent a “conflict.” It represents the fair market compensation anyone would expect for the work and dedication he endured to help advance this science.
Just because a physician earns income from his discoveries does not translate that they are somehow unethical as the Sentinel would have one believe. Inventors of all kinds of products every day wake up with the hope that they are creating something that will help others. If the products don’t work, people won’t buy them, doctors won’t use them and they won’t get receive income from their failed inventions. But if they are successful they should reap some reward so they are incentivized to invent the next beneficial product.
Conclusion
Since May of this year, Medtronic joined several drug companies in publicly listing payments to doctors – in advance of federal legislation that mandates such reporting beginning in 2013. Using this list only for purposes of criminalizing the collaboration of physicians with industry, the Sentinel points out only that “several of the doctors on that list are the same ones who wrote articles about the original Infuse clinical trial or who wrote about off-label uses for BMP-2.”
This characterization completely ignores the services and benefits created by the doctors. It does not go to explain the teaching or training impact it has had on other physicians, or the better outcomes and education patients will have when they learn about new treatments. Moreover, the Sentinel does not address the level of transparency and its effect on giving the public a greater sense of trust and integrity in Medtronic for disclosing such payments.
Instead, critics of this kind of collaboration maintain that when information comes from the manufacturers and people who are very vested in the product, the information is tainted, and it creates a conflict. But this claim is misguided.
Collaboration between physicians and industry remains absolutely vital to innovation in the medical technology industry. While some may believe the BMP-2 story highlights doctors being too “cozy” with industry, the reality is, the product is a success story in treating patients with back problems.