But none of that mattered to Cyberonics, which began to market its device directly to patients as well as doctors. While the company posted wildly positive testimonials on its website, there were no cautions in the promotional literature or videos about the seventeen deaths among the first one thousand patients implanted. Nor was there mention that the FDA had awarded only conditional approval of the device because of concerns about the high number of deaths, meaning that patients undergoing implantation were essentially guinea pigs in the quest to determine whether the device would be more likely to help them or kill them.
Between 1997 and mid-2005, sales of the VNS device were limited to the approximately thirty thousand individuals in the US with treatment-resistant partial epilepsy—a small subset of the estimated 2.4 million Americans with active epilepsy. Cyberonics needed to expand its market. Cummins was ready. The company had been taking out multiple patents on the VNS device, claiming that it could treat an array of medical problems, and the next condition the company wanted to tackle was depression.
Cyberonics said some epileptic patients experienced improvement in their moods after being implanted with the VNS device. This was potentially great business information. Depression is a huge healthcare crisis, affecting millions of Americans. If the VNS device could be sold as a treatment for depression, profits could dwarf those produced by the epilepsy market. The company launched a study to examine the role of VNS in depressed patients.
But the pivotal ten-week study of the VNS device in treating depression that Cyberonics submitted to the FDA was a bust: it showed no clinical benefit.123, 136 To make matters worse for Cyberonics, Suzanne Parisian, a former chief medical device officer at the FDA, reacted to Cyberonics’ failure to report sixty patient deaths during a single nine-month period, saying, “You have [sixty] people with epilepsy that had this implanted device [and] the FDA was never told that they died, and the company never did an investigation as to why they died, and the company’s contending that the device is safe and effective. It’s very unlikely that anybody will do any kind of an examination in these patients to find out why they’re dying, and then you’re asking them to expand the indication to depression patients.”137
Despite the company’s attempts to spin the depression study as positive, in 2004 the FDA issued a “non-approvable letter.” The VNS could still be used to treat epilepsy—but not depression.
None of that was about to stop Skip Cummins. He knew just what to do—and he had the power to do it. He authorized $440,000 in lobbying expenditures in 2005 to persuade the FDA to reverse its position. The lobbying funds were significant for a small company, comprising more than it had spent during any other year (for example, in 2009, with no other applications pending, the company spent $8,000 on lobbying).138
Cummins personally lobbied the FDA, insisting that the agency would be guilty of abandoning depressed individuals to death by suicide if it failed to approve the VNS device for depression treatment. He pointed to one-year follow-up data that he said showed benefit—though experts with Public Citizen would later point out that the data came from a poorly designed, “non-randomized, unblinded, non-concurrent control group” and that a mandated FDA analysis found “no statistically significant benefit on any…outcome.”123, 136 Cummins took a new tack—he enlisted former Democratic House majority whip Tony Coelho to be on the board of Cyberonics.139 Coelho’s career was marred by scandal. He’d resigned from Congress in 1989 following reports that he participated in a sweetheart deal involving a “troubled S&L operator” and the purchase of a $100,000 junk bond, and in 1998 he was found to have vastly overcharged the US government to support a lavish lifestyle.140 Nevertheless Coelho, who has epilepsy, proved to be a worthy ally to Cummins. After leaving Congress, he maintained extensive ties with top-level government officials and worked as Al Gore’s campaign chairman. He crafted the Americans with Disabilities Act and later served as chairman of the board of directors of the Epilepsy Foundation. Given that Congress holds the purse strings, the FDA could hardly dismiss Coelho, whose influence continued to be felt in political circles.
By July of 2005, Cummins’s strategy, with the help of Coelho, had paid off. The FDA approved the VNS device for “treatment-resistant depression.”
But the approval by Daniel G. Schultz, then the director of the FDA’s Center for Devices and Radiological Health, was awarded over the objections of nine FDA scientists who unanimously recommended against approval of the VNS device for the treatment of depression. It was the first time in the agency’s history that an FDA director had overruled the unanimous recommendation of FDA scientists.123, 136, 141 The resulting scandal, dubbed Devicegate, revealed that the agency had spied on the dissenting scientists, which led to a rancorous rebellion by nine of the scientists who filed a lawsuit against the agency. (We’ll return to that story in a later chapter.)142
According to the Union of Concerned Scientists, “By overruling his scientific advisors, Dr. Schultz set in motion a potential windfall for Cyberonics.”141 The ruling led to a $2.3 million overnight gain, on paper, for Cummins. Together, Cummins and Coelho reaped $50 million by trading a money-losing stock: the company had raised $175 million from investors by 2006 while chalking up $186 million in losses.139, 143
Investors were positively giddy about the approval. The financial website Seeking Alpha urged readers to buy Cyberonics stock in a story headlined WHETHER YOU SUFFER FROM DEPRESSION OR NOT, DON’T MISS YOUR CHANCE TO PROFIT FROM IT. The article noted that the Centers for Disease Control and Prevention estimated that one in ten Americans suffers from depression and that Healthline estimated that the number of people being diagnosed was increasing by 20 percent per year. Since half of them wouldn’t respond to the initial course of treatment, they predicted that about 5 percent of the US population (with a growth rate of 20 percent per year) would be candidates for the VNS device. Cyberonics estimated that some four million people in the US had treatment-resistant depression.
By then, Cyberonics was investigating some fifty-five conditions they thought the VNS device might be sold to treat, including anxiety, atrial fibrillation, autism, bulimia, burn-induced organ dysfunction, and drop attacks as well as fibromyalgia, heroin-seeking behavior, hiccups, multiple sclerosis, inflammation of the heart (myocarditis), obesity, rheumatoid arthritis, congestive heart failure, and ringing in the ears. The company had taken out patents for the device covering each of these indications.77
Cyberonics’ proposition that such a bizarrely wide range of ills could be treated with one device is reminiscent of the claims made by hucksters of an earlier era. Consider the promoters of the Violetta machine, which in many ways was the forerunner of the VNS device. In the early 1900s, the manufacturers of the device claimed that electrical impulses generated by their machine and applied through the skin via various attachments could cure everything from back pain and carbuncles to a stuffy nose and foggy thinking, along with a host of other ills.
Among the scientific oddities that curator Denny Daniel displays in his traveling Museum of Interesting Things are several antique medical devices, some of which look like instruments of torture. At the 2017 BIOMEDevice convention and exposition in Boston, he held up one device that looked a bit like a necklace made of thin rope with a few decorative beads attached. The convention engineers and techies gathered around and giggled nervously as Daniel explained that the “necklace,” which is attached to a “battery belt,” is meant to be placed around a man’s “special part.” The intended result? To transform him into a more “manly man.”
While there’s nothing new about unscrupulous device makers hocking their wares, most of the quack devices of yore were used externally. Now modern technology allows these devices to be implanted inside us, sometimes making them far more effective—but also far more dangerous. For example, the conch shell hearing aid (a real conch shell used to funnel sound into the external ear canal) has given way to cochlear implants, which can improve hearing much more tha
n a conch shell but which also can cause rare cases of fluid around the brain and meningitis. Daniel says he believes that many of today’s devices will end up in a museum display much like his—for people to laugh and shake their heads at.
Early hearing aid: Conch Shell Ear Trumpet, widely used until the early 1900s, replaced by external hearing aids and cochlear implants.
(Image courtesy of Denny Daniel, Director, Museum of Interesting Things, New York City)
This Violetta machine (circa 1920) applied “violet rays” of low current to various parts of the body to treat “brain fog,” stuffy nose, and impotence. Now implanted electrical devices are used for pain, Parkinson’s, seizures, depression, and more. (Public domain)
Dr. Sanden’s electric belt (circa 1892) applied electricity to a man’s “special part” to restore “life force” for a manly man. It was also said to treat kidney disease, nervous problems, backaches, rheumatism, congestion, and weakness. (Image courtesy of the Library of Congress)
From a business perspective, by 2005 Cyberonics could be viewed as a model of success in the world of the medical-industrial complex. It had used the pioneering work of a brilliant medical researcher, Eugene Braunwald, as the basis for building a burgeoning corporate empire. Unfortunately, the company’s climb to success had required it to ignore some of the hints of danger in Braunwald’s own study, to rely on research tests that provided only modest to nonexistent support for its claims of clinical benefit, and to use political influence to strong-arm a government regulatory agency into granting it approval over the objections of its own scientists.
Over time, these questionable tactics would come back to haunt Cyberonics. But in the short term, individual patients like Dennis Fegan, who put their lives in the company’s hands, would pay a serious price.
Chapter Five
Adverse Events
IT WASN’T LONG AFTER Dennis Fegan was discharged from the hospital in 2006 that he discovered a website devoted to people who had been implanted with a VNS device. The website, which hosts a message board run by a woman named Donna Baum, would have an enormous impact on Fegan’s future.
A friendly, round-faced woman with long dark hair, Baum recalls the intense anxiety she felt after her first seizure, which she had in 2001, at the age of forty-seven. Wanting information as well as the company of other people with her condition, she sought out an epilepsy support group. She found a local one led by an enthusiastic woman with epilepsy who told the participants she had had a device called a vagus nerve stimulator implanted in her chest to control her seizures. “She was so skinny,” Baum recalls, “you could see [the VNS device] poking right out on her chest. She said it was the most wonderful thing.”
Baum was eager to get help. Her seizure meds left her feeling groggy and confused. The suggestion that she might be able to use a device rather than drugs to control her seizures was a welcome prospect. So she, along with the rest of the group, was happy when the woman suggested bringing a Cyberonics representative to a meeting. They were even more delighted when they learned that the company would sponsor a free lunch presentation at a nearby hotel. When group members arrived, Cyberonics had placed a “gift bag” containing a promotional video and pamphlets on each person’s chair. It was one of many such “seminars” held across the country at which people with seizures were told about the benefits of having a VNS device.
Afterward, Baum says the company began a lengthy period of “courting” her. “Cyberonics started taking interest in me from that very first meeting,” she said, and she wasn’t the only member of the support group the company pursued. In the months that followed, Cyberonics representatives, she said, would “take us out to lunch, call every week, and ask how we were doing.” Baum was grateful for the attention. Fearful of having a seizure in public, she was hesitant to go out and mostly remained at home. The friendship of the Cyberonics representatives filled the void. They seemed to care about her. They listened to her with interest. And the free lunches were nice. “It wasn’t just McDonald’s, you know. They took us to Denny’s.”
She was especially excited to discover that Cyberonics sponsored a message board for patients on its website, a welcoming place for anyone with epilepsy, whether he or she had a device implanted or not. Here Baum found the community she had been seeking. People could discuss anything on the message board: the ins and outs of living with epilepsy, the mind-numbing drugs, the surgical options (including VNS), even personal problems. They cheered each other on, asked after each other, commiserated when things didn’t go well; they understood each other. Baum says the support members gave each other “was incredible.”
But not long after the message board was launched, disturbing posts began to appear.
As more people were implanted with the device, more complaints of unexplained symptoms surfaced. The message board began to resemble a complaint board, and anger mounted as the company failed to respond to questions. Were participants’ symptoms caused by the VNS device?
Cyberonics staff, previously solicitous, suddenly turned cold. They no longer responded with pleasantries. Nor were they inviting Baum out for lunch anymore. Then, without fanfare, Cyberonics simply pulled the plug on the message board and shut it down. Adam Feuerstein, a biotech analyst writing for TheStreet.com, said the abrupt action followed mounting complaints by patients who posted comments “critical of the company and its device.” One patient who posted critical comments, Elisa Driesen, told Feuerstein that the VNS “did nothing” to stop her seizures. She said the side effects of “constant pain, numbness, and breathing problems” were unbearable, adding, “My mission was to educate people…I wanted people to know what I was experiencing with the VNS. Now that the message board is gone, my greatest fear is that people won’t be educated now.”
Outraged that the company shut down the message board, Baum decided to take action. On February 18, 2004, one week after Cyberonics closed its message board, she opened a publicly accessible “VNS Message Board.” Anyone who entered “VNS” or “vagus nerve stimulator” and “support group” into Google could find it.144 So of course Dennis Fegan did, and his spirits lifted. Baum’s message board didn’t just connect him to others implanted with the VNS device, it was also a treasure trove of information.
Writing as “Birdbomb,” Baum posted a link on the message board to the FDA’s database of “adverse events,” or possible side effects related to medical devices. The database, known as the Manufacturer and User Facility Device Experience (MAUDE), includes voluntary reports from hospitals, manufacturers, and others of side effects associated with medical devices as well as mandatory manufacturer reports of life-threatening events and deaths.
Fegan began the hunt for Cyberonics’ report on his own experience. He recalled asking the Cyberonics representative, Steven Parnis, during their August 2006 encounter whether the company planned to file a report with the FDA about what had happened to him. Parnis did not give a straight answer to the question. Over the next few months, Fegan searched through thousands of reports of adverse events associated with the VNS device, and still no report from Cyberonics on his own incident appeared. Now Fegan understood why Parnis had been so noncommittal: it appeared that he may not have intended to file a report.
Parnis had also told Fegan and Bahamon that the company hadn’t seen other cases like his. But late one night, sitting in his bedroom-cum-office, with the only light coming from his computer screen, Fegan came across a case report of a patient admitted to a hospital with an abrupt increase in seizures. The report said the patient was found to have “severe asystolia” coincident with vagus nerve stimulation.145 By then, Fegan knew the words asystole and asystolia all too well. He could feel his pulse quicken. There it was—the very thing Cyberonics claimed hadn’t happened to anyone else: a patient’s heart had repeatedly stopped, and then, when the device was disabled, his normal heart rhythm was restored. Later, Cyberonics would claim that they had no reports of patients dying from asystole caused by
the VNS device.146 They conceded that they had four cases of asystole on file, but they said all of them occurred only during surgery and that all four patients recovered and did well.
Fegan wasn’t convinced. He continued to dig into the MAUDE database and found a number of cases in which patients developed drop seizures, yet they would have other symptoms or signs not typical of drop seizures, such as losing consciousness and turning blue. His own episodes had been mistaken for drop seizures, though he was in fact losing consciousness because prolonged asystole was causing him to pass out.
A January 2004 report Fegan found on MAUDE read:
[Patient] originally received the VNS system so that he could reduce the medications he was taking. The VNS did not appear to help, and the patient began to have recurrent and more frequent events. The patient reported that 80 percent of the seizures are without warning…and has difficulty breathing…His lips will turn blue and he will fall from standing. [The patient was admitted to the hospital, where the following was observed:] He went from his prior sinus [normal] rate to a progressive bradycardia [slowing of the heart rate], culminating in a 15-second pause [asystole]…There was concern that the VNS system may have contributed to the event, therefore the VNS device was deactivated.
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