Some of the nation’s most prominent spine surgeons hailed it as a medical breakthrough.
In a study of nearly 240 patients with
lover bag pain, the doctors said that the Prodisc, an artificial spinal disk, had worked much better than conventional surgery in which patients’ vertebrae were fused.
“As a surgeon, it is gratifying to see patients recover function more quickly than after fusion and return to their normal activities more easily,” Dr. Jack E. Zigler, a well-known spine specialist and one of the study’s lead researchers, said in a 2006 news release announcing the latest results of the Prodisc clinical trial.
As it turns out, Dr. Zigler had more than a medical interest in the outcome. So did doctors at about half of the 17 research centers involved in the study. They stood to profit financially if the Prodisc succeeded, according to confidential information from a patient’s lawsuit settled last year.
The companies behind the disks and the surgeons who were willing to comment say the researchers’ financial interests had no impact on findings of the research, which they say have been published in various peer-reviewed medical journals. The Prodisc, used on thousands of patients, has been shown to benefit many people with back pain, they say. It is unclear, however, whether the disk’s maker fulfilled its legal obligation to inform the
food and drugs administration of the researchers’ financial interests before it used the study’s results to approve Prodisc in August 2006.
Synthes, the current manufacturer, said it would not comment on whether the F.D.A. had been fully informed of the researchers’ interests. The F.D.A said it was investigating the matter.
In the study results submitted to the F.D.A., moreover, an unusually large number of patients were not included, and some of those patients have said they fared poorly. As a result, some patients and doctors critical of the research say the study may have cast the Prodisc in an overly flattering light.
The way the Prodisc was tested and approved provides a stark example of conflicts of interest among clinical researchers — conflicts that are seldom evident to doctors and patients trying to weigh the value of a new device or drug. Instead of serving as objective gatekeepers who can screen out potentially harmful or ineffective new devices or drugs, some medical experts say, clinical researchers with conflicts may have incentives to overstate the value of a new product for patients.
For better or worse, doctors in this country frequently have financial ties to the companies whose devices or drugs they recommend to patients. But in the case of the Prodisc clinical trial, as with any clinical research, the doctors were supposed to be acting not as advocates for the product but as objective scientists studying whether the disk was safe and effective enough to be widely sold and used in the United States.
“The surgeons themselves are guilty of being insufficiently critical of products and techniques they are developing,” said Dr. Richard A. Deyo, a medical professor at Oregon Health and Science University. “More people are interested in getting on the gravy train than on stopping the gravy train.”
One Prodisc study patient who says the surgery left her worse off, Patricia Kennedy, asserts her surgeon “seemed more concerned with the prospects for the Prodisc than for her medical care,” according to the lawsuit settled on undisclosed terms last year. The surgeon, Dr. Richard A. Balderston, who practices in Philadelphia, was one of the researchers with a financial interest in the disk. He referred questions to his lawyer, J. Scott Kramer, who declined to comment. Ms. Kennedy and her lawyer also declined to comment.
Most of the 11 other Prodisc investor-surgeons who were asked to comment also declined. But Dr. Kevin Foley, a Memphis surgeon involved in the study, says he put $20,000 behind the Prodisc because he considered it a promising technology. He said one patient, a schoolteacher, had trouble standing before her Prodisc but was able to go hiking afterward.
But Dr. Foley said some patients do not do as well after surgery and he favored
spinal fusion
for most.
Spinal Surgery Questions
The field of spinal surgery and devices has been riven with questions about the effectiveness of treatments. Some doctors and insurers say there is too little clinical evidence showing that back surgery works for most people, whether they get traditional fusion surgery or have a disk replaced.
Even though fusion surgery continues to be the treatment of choice, there is substantial debate over how many patients actually benefit from it.
Now, artificial disks are drawing skepticism. Thousands of patients worldwide have received the Prodisc, which sells for about $10,000 in the United States. But
medicare and several commercial insurers generally refuse to pay for the surgeries, which can cost tens of thousands of dollars.
And many of the Prodisc investor-researchers are now focusing their attention on newer spinal devices — often for companies with whom they also have financial ties. Dr. Zigler, for example, is a researcher for a new spine-stabilizing device made by Applied Spine Technologies, where he serves as a paid member of the company’s scientific advisory board.
But while doctors may easily move on to the next new thing, some patients are still coping with the aftermath of Prodisc procedures.
Calvin Timberlake, a 50-year-old former forklift operator who lives just outside Victoria, Tex., had a Prodisc implanted in his spine four months after the F.D.A. approved it; his surgeon was not involved in the clinical trial. He says the Prodisc subsequently came apart, forcing him to undergo a second emergency surgery to have it removed.
Mr. Timberlake, who says he remains in severe pain, is suing Synthes, but not the doctor, whom he does not blame for his problems. A spokesman for Synthes declined to comment.
Dr. Charles Rosen, a spine surgeon at the University of California, Irvine, was not involved in the Prodisc trial. But he provided his expert opinion to Patricia Kennedy’s lawyers and has reviewed the medical records of some of the other patients who are dissatisfied with their treatment. He is among a growing number of specialists who say the relationships between some prominent spine surgeons and the device industry have become too cozy.
“Industry’s goal is to make a profit for its shareholders, not to advance medicine,” said Dr. Rosen, who in 2006 saw a need to start a group called the Association for Ethics in Spine Surgery. It now includes 85 specialists who say one of their aims is to warn the public about industry influence on medical practice.
Investing in a Start-Up
Prodisc was developed by Spine Solutions, a privately held start-up company in New York that was jointly founded in 1999 by a German medical instrument maker and a New York investment firm specializing in orthopedics, Viscogliosi Brothers.
Anthony Viscogliosi, one of the three brothers running the firm, served as Spine Solutions’ founding chief executive and its chairman. The Viscogliosi firm operated a number of investment funds whose main asset was Spine Solutions.
Dr. Zigler, a spine surgeon at the Texas Back Institute, was the first doctor in the United States to perform the disk surgery in October 2001. Texas Back, widely considered one of the nation’s leading private practices in spinal medicine, has been among the most aggressive in advocating new devices like artificial disks.
The confidential documents show that Dr. Zigler invested at least $25,000 in early 2002 in a Viscogliosi Brothers fund created to finance Spine Solutions.
A venture capital fund run by the Texas Back Institute, meanwhile, had invested an additional $75,000 in the same fund. Other doctors at Texas Back were also investors, putting in an additional total of $70,000.
Dr. Zigler and the Texas Back Institute declined to comment except through a statement attributed to Dr. Zigler. “The integrity of clinical research trials is core to the successful advancement of spine and neck care and at the heart of Texas Back Institute’s commitment to provide leadership in the field,” it said, in part.
Other well-known surgeons who were researchers in the study and investors in the Viscogliosi funds included Dr. Frank P. Cammisa Jr., the chief spine surgeon at the Hospital for Special Surgery in New York. By the end of 2001 Dr. Cammisa had invested a total of $250,000. The hospital itself owned stock directly in Spine Solutions.
The hospital says that it no longer invests in companies whose products it is researching but that patients participating in the Prodisc study were told about the hospital’s and Dr. Cammisa’s financial interests. Through a hospital spokeswoman, Dr. Cammisa declined to comment.
Other prominent spine surgeons involved in the Prodisc research who also invested at least $100,000 with Viscogliosi Brothers included Dr. Balderston, Dr. Thomas J. Errico at
New York university and Dr. James Zucherman at St. Mary’s Hospital in San Francisco.
Through a spokeswoman at New York University, Dr. Errico declined to comment. Dr. Zucherman says financial interests do not affect how he conducts research.
Ethics and Financial Gain
Few would argue that doctors should never be allowed to invest in promising new technologies. But when doctors are acting as researchers, they should not have money riding on the outcome, in the view of outside experts like Dr. Kevin A. Schulman, a professor of medicine and business at Duke University Medical Center who helps oversee clinical research there.
Duke, Dr. Schulman said, would generally not allow a doctor with a significant financial stake in a drug or device to be involved in a clinical study of it. An exception might be made for a surgeon who invented a new device and had special expertise in its use, Dr. Schulman said. But the Prodisc doctors appear to be simply investors.
In a statement, the Viscogliosi Brothers said, “We are proud of the fact that so many distinguished surgeons have invested in our funds and it validates their individual views on Prodisc as a highly effective technology.”
The F.D.A.’s rules allow clinical investigators to have financial ties with the maker of the device or drug they are studying — on the condition that such relationships are fully disclosed. Lawyers who have worked with the F.D.A. say that when it becomes aware of potential conflict, it tends to subject research to a higher level of scrutiny.
The F.D.A. now says it is checking to see whether there was adequate financial disclosure information about the Prodisc researchers during the clinical trial and at the time that the subsequent application for approval was submitted.
In early 2003, the Viscogliosi Brothers found a buyer for Spine Solutions. Synthes, a large Swiss medical manufacturer, agreed to pay $175 million at the deal’s closing and another $175 million if some of the company’s devices, including the Prodisc, got regulatory approval.
In a deposition, Dr. Balderston, who said he had invested about $500,000 with Viscogliosi Brothers, said the Synthes deal increased the value of his investment by “about 10 percent, 20 percent, something like that.”
Dr. Balderston was already an investor when he was recruited for the F.D.A. studies by Spine Solutions, according to his deposition. He failed to disclose those ties, according to the court records, which indicate that the clinical investigator form he filled out did not mention his investments.
Dr. Balderston said in the deposition he did not believe that he was required to disclose his holdings in the funds. “There were a lot of people who invested,” he said, “so my small number was not a significant number.”
Results of Prodisc Trials
In early 2005, when Synthes submitted the Prodisc study to the F.D.A. as part of the company’s application for approval, it used results for 162 patients who had received the device and 80 who had spinal fusion surgery.
The results did not include 50 Prodisc patients who were considered “training cases” — surgeries performed to let doctors learn how to implant the devices. Such training is fairly common in device trials.
An additional 21 patients, about 10 percent of those studied, were also excluded from the reported results.
A Medicare official, Dr. Steve Phurrough, said 10 percent was unusually high. While it is impossible to tell what the outcome of the study would have been otherwise, Dr. Phurrough said, “it gives us pause.” The agency decided last August not to cover the disk for most Medicare patients.
Hratch Vranian, a 52-year-old mechanical engineer from Pasadena, Calif., was one of the training cases in the Prodisc trial, and he is among those involved in the clinical trial who say that their surgeons were not able to offer much further help after the Prodisc did not relieve their pain.
Synthes says that in any clinical trial there are patients who do not complete the study. The company defends the quality of the Prodisc study. Because the F.D.A is rigorous about how a study is set up and conducted, said a Synthes spokesman, Gilgian Eisner, “it is not so easy to influence the F.D.A. trials.”
Many of the Prodisc researchers have moved on to other clinical trials.
Some include products made by other companies promoted by the Viscogliosi Brothers, like Paradigm Spine. Dr. Errico at New York University, for example, is a clinical investigator of a new spinal implant made by Paradigm Spine.
Close relationships between surgeons and device companies can affect more than the potential quality of an individual clinical trial, said Dr. Drummond Rennie, a professor of medicine at the University of California, San Francisco who has studied conflicts of interest among physicians. Because the entanglements are so common, Dr. Rennie said, it is unlikely another surgeon will speak out about any potential misgivings they have about any device.
“The absolute ideal from a drug or device company is everyone is covered,” he said. “And what they have it covered with is money.”