The initial pain of the injury, instead of subsiding, as she had hoped, began to get worse. Severe nerve pain began shooting from her neck down her left arm and into her hand and fingers, which became completely numb. She saw a doctor who said she would need surgery. Pickett held off. She sought second, third, and fourth opinions, hoping the pain would just go away—or that she’d find a doctor who would tell her she didn’t need surgery. But every doctor told her the same thing: there was no way around surgery. After months of pain and sleepless nights, she finally turned to her colleagues in the Medtronic spine division for help and asked for the name of the best spine surgeons between Arizona and California.
A colleague gave her three names: Jeffrey Wang,* Rick Delamarter, and Todd Lanman. She saw Lanman, a Beverly Hills neurosurgeon and doctor to the stars (his office boasts pictures of Clint Eastwood, Liza Minnelli, and Sylvester Stallone). Lanman told her she would need “four levels” of repair—two artificial disks and two fusions.
Pickett says, “He showed me a couple of the [artificial] disks and said, ‘I’ll use a Medtronic and a Synthes [product].’ He mentioned Infuse. I had no idea what Infuse was. I’d never even heard the word before. He told me that he ‘may or may not’ use it.” She says when she asked what Infuse was, Lanman told her only that it ‘helps solidify the fusion.’” Pickett says she’s not one to hang back: she asks a lot of questions because, as she says, “I know too much.” She asked Lanman if there was anything she should be concerned about. His response, she says, was “laid back” and “reassuring.”
But Pickett knew that all surgeries carry a certain degree of risk. She told Lanman she wanted two things. She wanted her surgery to be performed at Cedars-Sinai, a hospital where she had corporate accounts and whose processes, which she described as excellent, she had come to trust. She also wanted her surgery done first thing on a Monday morning, when the OR was at its cleanest and the staff at its sharpest.
According to her legal complaint filed against Lanman and Medtronic,* Lanman, who had privileges at Cedars-Sinai, nonetheless told Pickett he preferred to do the surgery at Olympia Medical Center, which he referred to as a “boutique hospital,” because he had his own staff there. Pickett acquiesced.
The night before the surgery, Lanman’s office faxed Pickett a written consent form. “It was a consent form for carte blanche,” says Pickett. “It said he might use a variety of different devices, bioabsorbables, BMP—and I didn’t even know that BMP was Infuse, because that wasn’t the word he’d used.” She was alarmed by the list of potential complications: along with infection and bleeding were paralysis, stroke, and death. Pickett says she called Lanman’s office and told the staff, “‘I’m not signing this.’ But they told me, ‘Well, you have to sign it or you have to cancel the surgery.’ I asked to talk to Lanman, but they said he was in Hawaii and wouldn’t get in until the morning right before my surgery. I told them I still wanted to talk with him before I’d agree to surgery.”
The next morning, on June 25, 2012, she got to the hospital at seven. Pickett says Lanman came to see her just before 1:30 p.m. “He came in all cocky talking about his surfing trip. I said, ‘Hey, we need to talk about this consent form—it’s ridiculous,’ and he said, ‘Hey, kiddo, you have to sign this. You know how it goes: you have to sign stuff like this.’” He added, “You have nothing to worry about.” Exhausted, Pickett yielded. She says she felt bullied into signing the waiver.
“What happened next,” says Pickett, “changed my life forever.”
According to her complaint, Lanman implanted rhBMP-2 in Pickett’s neck. Several days after surgery, Pickett developed an intense inflammatory reaction that paralyzed her vocal cords. Doctors repeatedly injected steroids and fillers directly into her vocal cords in an attempt to allow her to recover her ability to speak normally. It was a scary time, because if the swelling didn’t go down, she could have trouble breathing, a complication that has forced some implanted patients to go on life support and even die.289, 307
Eventually she did recover from the inflammatory reaction, and though the numbness in her arm persisted, the pain began to let up. She returned to work full-time and continued to enjoy unusual success.
Then, five to six months after surgery, the nerve pain returned with a vengeance, affecting both sides of her neck. The pain in her left arm was “excruciating.” By this time, Pickett had done some reading and learned that BMP-2 can trigger ectopic, or excess, bone growth. She asked Lanman if that could be the problem, but he said no, that he’d just “missed a spot,” implying that the problem was caused by her underlying injury—not the device he’d implanted. Besides, he added, the claim about bony overgrowth was just some hype caused by overzealous attorneys trying to make money.
She sought second and third opinions from doctors who read the scans and told her that the cause of her pain was crystal clear: rhBMP-2 had indeed caused significant bony overgrowth and was impinging on her nerves. The excess bone would have to be carefully drilled away.
In May of 2013, she underwent revision surgery, this time by a surgeon in her home state of Arizona. When he opened her up, he described what he saw as a “shit show.” The bone was wrapped around her spine and nerves. He had to use exquisite care as he drilled away at the excess bone. Nonetheless, one of her vertebrae fractured as he attempted to free her nerves from the mass of excess bone.
By that time she had asked her boss to file an incident report regarding the accident at the team-building event. If nothing else, she wanted to file for worker’s compensation to help pay for her medical expenses (even though she’d continued to work full-time, she was paying extensive medical bills out of pocket and with her private health insurance), and she needed the incident report to show that her injury was work-related. She also asked for medical articles about complications related to the device. But, she says, Medtronic dismissed her concerns, saying that “hungry attorneys” were creating unnecessary panic. If she wanted medical articles, she’d have to get them from her surgeon. She scoffs, “Clearly that wasn’t going to happen.”
She told her boss she had to undergo a second surgery because of bony overgrowth caused by rhBMP-2, and she thought an adverse event report should be filed with Medtronic’s Office of Medical Affairs. But he demurred. So Pickett went to Medtronic’s Tempe, Arizona, office and filed an adverse event report herself.
Suddenly, despite her continued excellent work ratings, Medtronic informed her that her position was being eliminated. She was out of a job.
After two operations, out of work, in pain, and facing the possibility of even more surgery, she finally decided to file suit against the company she loved. In the process, she, like Lew before her, would learn a good deal about the device implanted in her neck—and the stupendous sums of money involved.
One of the first things she learned about was the FDA warning issued in 2008, four years before her surgery, notifying healthcare providers that rhBMP-2 used in the cervical spine was associated with “life-threatening complications.”288 The agency urged practitioners to “either use approved alternative treatments or consider enrolling as investigators in approved clinical studies.”
Why hadn’t Lanman told her of this warning?
Then, according to her complaint, she learned something else about Lanman: he was a prominent consultant for Medtronic, which had paid him more than $1 million in fees and royalties. Not only had he failed to tell her about the lavish payments he received from Medtronic, he also didn’t tell her the reason he may not have wanted to do the surgery at Cedars-Sinai: he couldn’t do the surgery there, because the hospital had significant restrictions on the off-label use of rhBMP-2 due to its known harmful effects. But, according to Pickett, in her complaint, Lanman’s “boutique” hospital, Olympia, had no such prohibition.
Pickett says that when she asked her Medtronic colleague who specialized in spine devices about Infuse, he didn’t tell her its use in the neck would be off-label. “The only thing he sa
id was, ‘It’s great stuff.’” She says she never would have agreed to be implanted with rhBMP-2 if she had been told about the dangers of its off-label use. She says Medtronic’s official position is that representatives shouldn’t promote off-label use: “We’re told to walk out of the room if a doctor uses a device off-label.” She says they played it by the book “one hundred percent” in the cardiovascular section.
Nonetheless, off-label sales are the bread and butter of orthopedic surgeons using rhBMP-2, and some of the largest users of rhBMP-2 are surgeons with ties to Medtronic.287, 296, 297
How did off-label use of rhBMP-2 come to be such a common practice among surgeons if manufacturers are prohibited from promoting devices and drugs for off-label use?
Sales representatives are quick to say that there is often an implicit “wink-wink, nod-nod” attitude about off-label promotion—a strategy that ensures a financial boon for both the company and its reps. Sales reps say the pressure to meet sales quotas is enormous—so enormous that it can, and does, lead to the use of widespread illicit tactics by companies and reps.
Former Cyberonics representative Andrew J. Hagerty, joined by the US government, charged in a whistle-blower lawsuit against Cyberonics that bosses at the company set sales quotas for the VNS device that its reps could only have met by participating in illicit promotions.308, 309 According to the complaint, if reps failed to meet 75 percent of a revenue goal in a single quarter, they would be put under a special supervisory plan, and if they didn’t fully meet their quotas the following quarter, they were terminated. But companies typically employ both carrots and sticks, and the complaint stated that “almost one-third of sales representatives earned more than $360,000 per year with more than 66 percent of that amount coming from commissions.”
The combination of potentially fantastic earnings and the constant threat of being fired for “underperforming” can lead representatives to engage in unethical and fraudulent practices. When one top-performing rep was found to have created her own marketing materials, which hadn’t been approved by the company (and therefore may have violated the FDA’s approved labeling of the VNS device), Cyberonics didn’t fire her, nor did it take away her high-earner commissions. Instead it simply withheld an all-expenses-paid trip to her choice of Alaska, Hawaii, Tahiti, or the Bahamas. In this way, representatives—like their companies—learn that paying certain penalties is merely the cost of doing business.
Companies and their reps beef up sales by cultivating doctors through a combination of flattery and “consulting,” or speaker’s, fees, and Hagerty’s suit exposed the multilayered conflicts of interest that connect industry and doctors in the promotion of off-label prescribing and outright fraud.
Pickett hopes that her suit will create awareness of the fact that patients need to ask a lot of questions. She says, “Don’t assume your doctor is making the best decision for you. Some may make the decision best for their pocket.”
One doctor who has an intimate understanding of industry influence is Daniel Carlat, associate clinical professor of psychiatry at Tufts University School of Medicine. Carlat was flattered when a Wyeth drug representative asked him in 2001 to give talks to other doctors about its antidepressant drug venlafaxine (marketed in the US as Effexor XR). He’d be paid $500 for a one-hour talk over a free lunch—$750 if he had to drive for an hour to get there.310, 311
Carlat, who specializes in psychopharmacology, says he didn’t believe at first that he was doing anything wrong when he agreed to give the talks. He was familiar with studies showing that the drug might be more effective than some older antidepressants. Since he had already prescribed the drug to a few patients with some success, he reasoned that he would be doing nothing unethical by talking about the drug’s benefits.
The company flew Carlat and his wife to a “faculty development” program in New York City, where they were put up for two nights at a luxury hotel and given tickets to a Broadway show. Carlat quickly discovered that some of the biggest names in psychiatry were also attending—and benefiting from Wyeth’s largesse. It was a heady experience. While there, Carlat ran into an old colleague who mentioned that he was giving talks promoting gabapentin (Neurontin) for Warner Lambert—a drug he said was “great” for some patients with bipolar disorder. Carlat was surprised by his old friend’s claim because of his own experience of prescribing the drug and because a study of gabapentin prescribed for bipolar disorder showed that the drug failed to perform better than a placebo. In a comedic moment, Carlat, seemingly oblivious to the process he himself was undergoing, wondered whether his colleague’s “positive opinion had been influenced by the money he was paid to give talks.”
After attending the faculty development program, for which he received an honorarium, Carlat was off and running, teaching doctors about venlafaxine. Over time, however, Carlat learned about some problems with the drug and decided to give more balanced presentations. At the very next talk, when he was open about the limited efficacy and side effects of the drug, Wyeth representatives took note. A corporate district manager was dispatched to follow up with Carlat and let him know that the company was aware that his most recent presentation was less “enthusiastic” than usual. Then, in a moment that would prove to be the grenade under Carlat’s feet, the manager asked Carlat, solicitously, “Have you been sick?” It was Carlat’s moment of truth.
Carlat wasn’t sick. Although he says it’s possible that the district manager’s question about his health was a genuine expression of concern, it was this question—and its timing—that brought everything into focus for him. It made him realize, as he later said, “something I would never, never have predicted happened: I ended up being a cog in their marketing machine.”
Carlat immediately resigned as a speaker for Wyeth and decided that the best way to atone for the inflated picture he’d painted about venlafaxine and the $30,000 he had received for giving talks over the previous year was to go on a “march of shame” in which he would give free “undrug talks” to any group that asked him to. By “coming clean” with his story, Carlat said, “I’m hoping to convince doctors to give up their addiction to industry money. Ultimately, our professionalism is at stake. We want our men and women to come in from the dark side.”
Fortunately he didn’t try to put a pretty face on his own behavior. In his own account, published in the New York Times, he described how drug companies bring doctors into the world of industry-sponsored “medical education”—and how doctors may embark on such relationships without any intent of harm or deceit but can nevertheless be slowly seduced into questionable behaviors, such as making pumped-up claims of drugs’ effectiveness while failing to give full weight to their side effects. In the article, Carlat presents his conduct warts and all, and you can almost smell his sweat as he quivers before a fellow doctor who, he fears, sees him for what he is: “a drug rep with an MD” degree.
In January of 2003, he launched the Carlat Psychiatry Report. Its website states, “We receive no corporate funding, which allows a clear-eyed evaluation of all available treatments.”
Each player in the dramas that Lew, Pickett, and Carlat were caught up in, including the surgeons, the hospitals, the manufacturers, and manufacturers’ representatives, stood to benefit financially by promoting the companies’ respective products and by obscuring their very real dangers. There is no conspiracy in any of this—just a confluence of interests that stretches across the entire healthcare industry.
Chapter Eleven
Breakdown
DENNIS FEGAN REMAINED CONVINCED that the VNS “cure” caused his asystole—and probably the deaths of many less fortunate individuals. He wanted the FDA to pay attention. And if it wouldn’t, he’d make sure the world knew.
Fegan sent an e-mail query to the FDA asking why seizures weren’t listed as a potential side effect of the VNS device. On April 24, 2009, he received an e-mail he wasn’t supposed to see. Ann Costello, the FDA reviewer who had served on the panel to approve t
he VNS device, accidentally responded to an e-mail thread started by Fegan’s inquiry by clicking “reply all.” It was a hasty click, and she must have instantly regretted it. The discussions that followed Fegan’s original e-mail were supposed to be internal FDA deliberations. Costello immediately put out a recall on the e-mail, but it was too late. Within seconds, Fegan had the draft version of the FDA’s response, along with suggested edits. The original, unedited message read:
Dear Mr. Fegan,
This is what I have heard from our Office of Device Evaluation:
The most current approved labeling listed with FDA has potential for increased seizures…and it is as a side effect. It was in the original labeling, removed and was subsequently told to be put back in. Approved per supplement 63.”
Thank You,
Joseph Tartal, Technical Branch Chief
In response to Tartal’s draft version, Costello wrote:
“I would delete the statement ‘It was in the original labeling, removed and was subsequently told to be put back in. Approved per supplement 63’ as this is not public knowledge.”
Not public knowledge? Whom was the FDA protecting? Itself? Cyberonics? Had the agency granted permission to the company to remove seizures as a listed side effect? The information was put back in the company’s manuals in December of 2008, but it was not to be found in an earlier version.
Costello’s e-mail made one thing clear: the FDA seemed more concerned with protecting Cyberonics and itself than with protecting the public interest.
The Danger Within Us Page 22