A new investigative report in Fortune magazine tells the chilling and tragic tale that unfolded when a medical device company decided to make an end run around federal regulators and market its product directly to orthopedic surgeons for an unapproved (off-label) use.
The company is Synthes, which makes plates, screws and other implants used to stabilize and mend bones. Its North American headquarters are in Pennsylvania.
“Between 2002 and 2004,” writes reporter Mina Kimes, “Synthes had tested a product called Norian XR, a cement that has a unique capacity to turn into bone when injected into the human skeleton. The Food and Drug Administration explicitly told Synthes not to promote Norian for certain spine surgeries [called vertobroplasties], but the company pushed forward anyway.”
They did so despite warnings that the product was unsafe when used in the spine, including the disastrous results of one of their own animal studies. Writes Kimes:
In the spring of 2002, [the Synthes manager in charge of Norian] received an unsettling e-mail from Dr. Jens Chapman, an orthopedic surgeon at the University of Washington who was working, along with his colleague [Dr. Sohall] Mirza, on the animal study funded by Synthes. The early results were alarming. Chapman informed [the manager] that when Norian was injected into the bloodstream of a pig, “the entire pulmonary artery system had clotted off.” As he put it, “We were expecting to kill the pig … but not suddenly and with a relatively small dose.”
… The surgeons had injected Norian into a large vein leading to the animal’s heart to simulate what would happen if the cement leaked during [human] vertebroplasty. The pig’s blood pressure plunged. When the scientists cut into it after its demise, they noted that volumes of blood clot containing Norian had amassed in its lungs. The animal had died in less than 30 seconds.
In December 2002, the FDA approved the use of Norian for general use in the spine, but not for the treatment of spinal compression fractures. Yet, reports Kimes, Synthes went ahead and
began training spine surgeons to mix [Norian] with barium sulfate [a mixture the company now called Norian XR] in order to perform vertebroplasties — an act explicitly prohibited by the label. …
The fact that Synthes couldn’t promote XR for its target market without first proving its safety in a human clinical trial didn’t seem to bother its executives. [One] sent the vertebroplasty team a celebratory e-mail. “Let me take a moment to congratulate the four of you [on] getting XR approved,” he wrote. “Very Well Done!”
Less than a month later Dr. Barton Sachs, a spine surgeon in Texas, used Norian to treat a VCF. His patient, a 70-year-old Oklahoma native named Lois Eskind, said beforehand that she was in excruciating pain and that she’d “rather have surgery than live like this.” Fifteen seconds after Sachs injected the cement into her spine, Eskind’s blood pressure plummeted. As a Synthes sales representative looked on, Sachs attempted to resuscitate her for 30 minutes before she died.
At least four other patients who had Norian injected into their spines died on the operating-room table before the FDA got wind of what was going on with the off-label promotion of the product and stopped it.
In 2009, a grand jury indicted Synthes and four of its executives. In 2010, the company pled guilty and agreed to pay $23 million in fines. Then, in 2011, in a remarkably unusual occurrence for such cases, the four executives were each sentenced to up to nine months in prison. They just completed those sentences this summer.
But Hansjorg Wyss, the Swiss-born, multi-billionnaire businessman who heads the company and who Kimes suggests was the driving force behind the off-label marketing of Norian, did not go to prison. He wasn’t even indicted.
‘A medical horror story’
Fortune magazine calls the Synthes saga “a medical horror story” and “a disturbing tale of corporate crime and punishment.” I agree, and highly recommend Kimes’ meticulous recounting of it. The details are deeply troubling — particularly how easy it was for the company to persuade orthopedic surgeons to use the untested product for unapproved uses.
But, as Kimes notes, such uses are not uncommon:
The FDA does not regulate doctors’ activity; as a result, off-label prescribing is ubiquitous. A 2006 study in the Archives of Internal Medicine examined hundreds of millions of prescriptions and found that more than 20% were written for off-label use. “A surgeon can prescribe anything,” says a former Synthes employee. “If he says, ‘Let’s put a bowling ball in your body,’ he can do it.” Physicians are quick to note that, because the FDA’s approval process can be frustratingly slow, off-label drug and device usage is a crucial part of health care.
Surgeons regularly use devices in unapproved ways. The culture of orthopedic surgeons is particularly aggressive. Predominantly male, “orthopods” are the jocks of the surgical world. Sales representatives tell stories of doctors playing loud rock music in the operating room and throwing instruments at the wall when they get frustrated. Several surgeons tell Fortune they simply don’t have time to pore over labels. [One surgeon] offers a blunt appraisal: ” ‘Off-label’ is not at all a pejorative term — it’s almost the opposite. Reading the label is for people who read labels.”
Surgeons don’t always listen to the FDA, but they do heed the young sales representatives who bring them devices and routinely watch them operate. “It sounds ridiculous, because here’s a guy who went to medical school and did his residency, and he’s listening to some guy in the back of the room,” says one former Synthes salesperson. Another adds: “It’s not uncommon to have a surgeon with a drill in his hand, about to drill a hole, looking over his shoulder at you saying, ‘Is this right?’ “
Footnote: In 2009, two randomized controlled clinical trials found that vertebroplasty was no better than sham surgery at relieving pain from osteoporosis-related spinal fractures. Orthopedic surgeons continue, however, to perform the procedure.