Patient beware: Being part of a clinical trial is a trial indeed
(September 2013) A highly unpleasant spotlight, which turned me into a Vagus showgirl for five years, has finally been turned off. I just completed a Cyberonics, Inc., clinical trial of the Vagus Nerve Stimulator, to assess its effectiveness in helping those who suffer from treatment-resistant depression. It was a ridiculous, scandalous experience.
I don't trust Big Pharma, and I don't trust the multibillion-dollar medical device industry. My cynicism was vindicated by the bizarre combination of incompetence and ruthlessness that characterized this study.
Beware of becoming part of a clinical trial. Your privacy, as well as your time and well-being, may be seriously jeopardized.
In trial after trial, the VNS device that was being tested in the study that involved me, has shown itself to have extremely limited value (up to a 90 percent failure rate). But Cyberonics (which sounds like a sci-fi cabal that unleashes evil robots), is determined to keep trying until it wears down its opponents and qualifies for CMS (Medicare and Medicaid) reimbursement, so it can achieve its dream: a fabulous financial windfall. (UPDATE: On Dec. 1, 2014, it was rejected again, as being "unproven and unnecessary," even though the ever-sloppy FDA approved it 10 years ago.)
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| The wire, which coils around the nerve, becomes thoroughly enmeshed in the tissue. |
I am thrilled to report that Medicare, Medicaid and the nation's insurance companies are holding their ground, finding Cyberonics' latest clinical trial to be as underwhelming as all the others. They are "flatly refusing" --in virtually every case -- to pay for the device, the surgery, and the lifetime of after-care that is required, according to the Washington Post.
The U.S. Centers for Medicare and Medicaid Services (CMS) is continuing to refuse reimbursement, despite the fact that the Food and Drug Administration (FDA) -- in its laziness, inconsistency and vulnerability to pressure -- half-heartedly approved the VNS for treatment-resistant depression nearly 10 years ago. That decision has inspired disbelief and ridicule ever since.
I have been informed that the refusal of Medicare and Medicaid to pay for an FDA-approved device is unprecedented.
And the CMS ruling that "VNS has no treatment effect," raised new concerns about the FDA's 2005 decision to approve VNS for patients with treatment-resistant depression, the Post reported.
Thus, the Cyberonics people are still conducting studies -- as if their device is going to evolve spontaneously into something worthwhile, if they just keep cutting people's necks open and putting it in. I believe this is what is known as "magical thinking" (although I also regard it as technological vampirism).
The firm had announced that it would conduct no further trials -- which cost several millions of dollars each -- unless it could find a partner. Year after year, it could not convince anyone to get involved, but its trials continued.
"We will not rest until all eligible patients have full parity in access to VNS Therapy," George Parker, Cyberonics' then-interim chief operating officer, told the Post in 2007, after yet another round of trials failed to show that VNS is "safe or effective."
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| Note how the lead is clamped to the vagus nerve in the bottom right view. Comfy! |
"No one wants to touch this company with a 10-foot pole," one commenter said on an investment advisor message board. "The failure rate of VNS is simply outrageous. It works less often than a placebo. I've never heard of that happening before."
In this article, I am going to describe my personal experience as a participant in the most recent trial, beginning in 2008. I will also address the dismal results of past studies (whose weaknesses have been replicated in subsequent studies); the outraged reaction of the scientific community to the FDA's approval of the device in 2005; and the shameless persistence of Cyberonics in pressing for reimbursement, despite the well-documented likelihood that the $30,000 to $70,000 cost per patient, just for the initial implant, would be a complete waste. I will also detail the substantial dangers and side effects of this product.
UPDATE: (http://www.nytimes.com/2014/05/25/magazine/can-the-nervous-system-be-hacked.html?nav). "(Neurosurgeon) Kevin Tracey’s efforts using vagus nerve stimulation have helped establish what is now the growing field of bioelectronics. He has grand hopes for it. “I think this is the industry that will replace the drug industry,” he told me. Today researchers are creating implants that can communicate directly with the nervous system in order to try to fight everything from cancer to the common cold....These devices are indiscriminate, blasting electricity into billions of neurons and hoping for the best. Conceptually, bioelectronics is straightforward: Get the nervous system to tell the body to heal itself.....(Unsurprisingly) in August, GlaxoSmithKline invested $5 million in SetPoint, and its bioelectronics R. & D. unit now has partnerships with 26 independent research groups in six countries. Glaxo has also established a $50 million fund to support the science of bioelectronics and is offering a prize of $1 million to the first team that can develop an implantable device that can, by recording and responding to an organ’s electrical signals, exert influence over its function. Instead of drugs, “the treatment is a pattern of electrical impulses,” Famm says. “The information is the treatment.” In addition to rheumatoid arthritis, Famm believes, bioelectronic medicine might someday treat hypertension, asthma, diabetes, epilepsy, infertility, obesity and cancer...UPDATE: (http://www.nytimes.com/2014/05/25/magazine/can-the-nervous-system-be-hacked.html?nav). "(Neurosurgeon) Kevin Tracey’s efforts using vagus nerve stimulation have helped establish what is now the growing field of bioelectronics. He has grand hopes for it. “I think this is the industry that will replace the drug industry,” he told me. Today researchers are creating implants that can communicate directly with the nervous system in order to try to fight everything from cancer to the common cold. Conceptually, bioelectronics is straightforward: Get the nervous system to tell the body to heal itself.....(Unsurprisingly) in August, GlaxoSmithKline invested $5 million in SetPoint, and its bioelectronics R. & D. unit now has partnerships with 26 independent research groups in six countries. Glaxo has also established a $50 million fund to support the science of bioelectronics and is offering a prize of $1 million to the first team that can develop an implantable device that can, by recording and responding to an organ’s electrical signals, exert influence over its function. Instead of drugs, “the treatment is a pattern of electrical impulses,” Famm says. “The information is the treatment.” In addition to rheumatoid arthritis, Famm believes, bioelectronic medicine might someday treat hypertension, asthma, diabetes, epilepsy, infertility, obesity and cancer...(But) if large numbers of patients someday choose bioelectronics over drugs, another issue awaits resolution: security. Bioelectronics devices will feature wireless connectivity so they can be fine-tuned and upgraded, “just like the software on your iPhone,” Famm says. And wireless means hackable, an unsettling fact that worries two experts on medical-device security."Yet if large numbers of patients someday choose bioelectronics over drugs, another issue awaits resolution: security. Bioelectronics devices will feature wireless connectivity so they can be fine-tuned and upgraded, “just like the software on your iPhone,” Famm says. And wireless means hackable, an unsettling fact that worries two experts on medical-device security."
IF I WANTED TO "TELL ALL," IT WOULDN'T BE TO A CORPORATION
Before I detail the absurdity of Cyberonics profit-driven war for approval, I will chronicle the traumatic loss of privacy that my involvement in this clinical trial required. It was a violation that has had an ongoing effect on me. I initially refused to sign on the dotted line, because I was distressed by the "laying bare" of my mind and my life that was being demanded by Cyberonics. I eventually relented, as a favor to a friend who was involved in administering the study at one of the sites, and who was desperate to cobble together an adequate sample.
I vehemently declined, though, to have the VNS appliance implanted in me (and not just because they expected ME to pay the $30,000 cost), so I was enrolled in the control group. All of us -- two groups of severely depressed patients -- had to essentially turn everything about ourselves over to this enterprise.
It made me sick. It left me with an ongoing sense of vulnerability. I lost something that I can never retrieve. I am "out there," instead of "in here." For better or worse, this blog -- which I launched about midway through the study -- has often been perhaps overly personal. Thanks to that stupid study, I feel that I have nothing left to hide.
We should not give up the right to hide -- particularly not for the purpose of enhancing the profitability of a corporation.
BECOMING A STRIPPER FOR THE VAGUS GUYS
Even though I didn't have my neck torn open and have a foreign object jammed into me, I was required to authorize the release of a lifetime of medical and psychiatric records, medical insurance records ( to reveal my "health-care utilization"), hospital records, records from individual doctors (including, Cyberonics specified, my gynecologist), and all of the personal insights gleaned about me during the study. The consent form acknowledged that the probing of study personnel "may upset you and worsen your depression."
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| Don't you love being probed by legal aliens? |
"Every reasonable effort will be made to keep the information private," Cyberonics assured study participants in writing.
I was repeatedly assured that my privacy would be honored, that I would be "nothing but a number," and that none of my information would be "personally identifiable."
That was patently untrue, as the fine print in the lengthy Cyberonics consent form acknowledged:
The information we share with others may include information that
directly identifies you. The Food and Drug Administration (FDA), will have access. There are
other federal agencies that may need to view the
data.
The study sponsor, its representatives and contractors, regulatory authorities and other supervising bodies may look at all your medical information.
Tests or examinations that you will be required to take may identify you because they may contain your name, address, telephone number, date of birth, social security number, race or ethnic origin, height, weight or other unique identifiers.
Once information is disclosed to outside groups, this information may no longer be covered by the federal privacy protections.
If your protected health information is disclosed to a recipient who is not a "covered entity," your protected health information may no longer be protected by federal or state law and may be subject to re-disclosure by the recipient.
If you revoke this authorization, we will not be able to collect new information about you, and you will be withdrawn from the research study. However, we can continue to use information we have already started to use in our research, as needed to maintain the integrity of the research.
Your information may be used by Cyberonics in connection with the sales and marketing of its VNS Therapy System.
This authorization does not have an expiration date.
The study sponsor, its representatives and contractors, regulatory authorities and other supervising bodies may look at all your medical information.
Tests or examinations that you will be required to take may identify you because they may contain your name, address, telephone number, date of birth, social security number, race or ethnic origin, height, weight or other unique identifiers.
Once information is disclosed to outside groups, this information may no longer be covered by the federal privacy protections.
If your protected health information is disclosed to a recipient who is not a "covered entity," your protected health information may no longer be protected by federal or state law and may be subject to re-disclosure by the recipient.
If you revoke this authorization, we will not be able to collect new information about you, and you will be withdrawn from the research study. However, we can continue to use information we have already started to use in our research, as needed to maintain the integrity of the research.
Your information may be used by Cyberonics in connection with the sales and marketing of its VNS Therapy System.
This authorization does not have an expiration date.
Before the trial had even formally begun, I inadvertently discovered that a description of my "personally identifiable" sexual
history, which I had mentioned to a therapist, had been shared among study personnel, including a secretary.
Input I have received from others who have been involved in Cyberonics trials indicates that study participants' personal revelations in general were handled in a cavalier fashion, which was not appropriate for any kind of patient information, particularly that which is so intimate.
My records, dating back 45 years to the present, contain vivid
accounts of devastating and degrading experiences,
disturbing thought processes and nightmarish phases of my life, in which my mental illness, eating disorders and substance abuse came close to killing me. In my interrogations by study personnel, I described extreme aspects of neurosis, sociopathic impulses, compulsive behavior and suicidality.Input I have received from others who have been involved in Cyberonics trials indicates that study participants' personal revelations in general were handled in a cavalier fashion, which was not appropriate for any kind of patient information, particularly that which is so intimate.
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| An Austrian artist group expressed disdain for male-dominated culture, psychiatry and sexuality, with VNS as a target. |
Depression support organizations? Don't they host "fun runs" and have web sites that provide message boards and lists of resources? They don't have a right to my life story!
My information would also be made available to personnel at the university from which I graduated.
And I don't want Cyberonics using me to fuel its propaganda machine, spreading the word at all levels of the Depression Industry that its device should be sold to vulnerable patients. But of course, that's exactly what it's doing.
And it's doing a masterful job of generating favorable coverage on many web sites, in medical journals and in the mass media, based upon study data that informed experts find "astonishingly weak."
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| My secrets, kept forever, in a vault that has a big welcome mat. |
KISS YOUR PRIVACY AND SENSE OF DIGNITY GOODBYE
Instead of its pathetically weak reassurance that, "Every reasonable effort will be made to keep the information private," why didn't the company make a forceful guarantee: "Cyberonics pledges that your privacy will be fully protected, and it has in place a protocol that makes it impossible for any personally identifiable information about you to be accessed by its own personnel, or by anyone else. Cyberonics agrees to be legally and financially liable for any breach. Any injured party will be eligible for both punitive and compensatory damages."
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| (Just kidding) |
No wonder Cyberonics has so much trouble finding anyone to participate in its clinical trials. This is ridiculous! Does the firm always rely on study administrators using their personal friends, like me, who grudgingly agree to be involved in such a debacle?
I haven't trusted the United States government to respect my privacy since the 1960s. Now I know not to expect a faceless corporation with no accountability, no loyalty and no evident integrity to do so.
I jokingly told clinician that a laptop containing all of our information would probably be stolen during the study, and that is exactly what happened, about two years into the process.
In order to sustain my commitment to participate, I had to repress my humiliation, even more after the theft. It was hard on me.
Every few months, for five years, I had to answer very personal questions, on detailed forms, and in separate interviews with a psychiatrist and a psychologist. By personal, I mean everything from "feelings of worthlessness" and "obsessive thoughts" to detailed inquires about my sexuality, including the amount of lubrication I was producing. These latter questions I refused to answer on the forms we had to fill out regularly, and a study assistant said, "Don't worry -- we'll fill those in for you."
Oh great! I wonder what sort of answers about lust and responsiveness have been attributed to me. Maybe it's so lurid, someone will make a movie about it: "Lilith: The Nympho Resurfaces."
All of this, and all my other records, are now -- and forever will be -- the property of Cyberonics, Inc., that ever-so well-lubricated machine.
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| I'm stimulated all right -- by indignation. |
I lost an aspect of precious autonomy and discretion for the benefit of a piece-of-crap device made by a haughty, hapless profiteer.
Even the FDA, which inexplicably approved the VNS device, was so lukewarm in its announcement, it could reasonably be regarded as a repudiation of Cyberonics. It began by referring to the initial, and best-designed, round of trials, in which VNS therapy was shown to be no better than a placebo. The federal regulator stated:
Based on the results of a
clinical study of over 200 patients conducted in the United States, during the
first 3 months of therapy, patients who had the device implanted and turned on
did not show any significant advantage in response compared to patients in whom
the "sham" device was implanted but not turned on. At 1 year, approximately 2 or 3 out
of every 10 subjects had a clinically significant improvement in symptoms of
depression.....and continued to have a similar degree of response through 2
years.
The remainder of the patients, however, had no improvement in
symptoms, and some actually got worse. This therapy is intended to be given
along with other traditional therapies, such as medications and ECT, and
patients should not expect to discontinue these other treatments, even with the
device in place. Patients will require regular visits to their physicians for
adjustments to their device and other treatments. By "clinically significant," the FDA meant at least a 50 percent improvement in patients' severe, debilitating depressive symptoms. And 70-80 percent did not even get that.
Just prior to granting its approval, the FDA sent a 3,256-word warning letter to Cyberonics noting that its devices were "adulterated." The letter went on to enumerate a wide-ranging list of serious violations following an inspection of its facilities.
These violations included:
"Failure to completely investigate and evaluate the cause of each medical adverse event; Failure to establish and maintain adequate procedures for validating the device design to ensure that the device conforms to user needs and intended uses and include design testing under actual or simulated use conditions; Failure to investigate the cause of nonconformities relating to product, processes, and the quality system; Failure to analyze processes, work operations, and other sources of quality data to identify existing and potential causes of non-conforming product; Failure to implement and record changes in methods and procedures needed to prevent and correct identified quality problems; Failure to establish and maintain procedures for implementing corrective and preventive action; Failure to establish and maintain procedures for receiving, reviewing, and evaluating complaints."
The FDA added that Cyberonics' responses to previous warnings "have not satisfactorily addressed the underlying issues," and "did not provide any supporting information or evidence."
And then the FDA gave its blessing to Cyberonics and its product. What a country!
Cyberonics had been forced to acknowledge that, "less than one in three or one in four patients (depending on the rating scale used) appeared to respond to VNS therapy," but that didn't seem to hurt its case.
In Phase II trials, the device performed even more poorly, with a 90 percent failure rate. I learned this not from Cyberonics, which continues enthusiastically to market VNS for depression, but from a clinician who had seen the most recent data in documents that are not publicly available.
Severely depressed patients who are pressed to try VNS treatment are not informed that it is very unlikely to help them, that it will cost them tens of thousands of dollars for the initial implant and at least tens of thousands of dollars in lifetime after-care.
Much has been reported in recent years about the unsatisfactory performance of antidepressant medications. But even they were required to reach a higher benchmark of proof before gaining FDA approval.
Cyberonics' marketing materials claim that "VNS therapy delivers long-term benefits that improve over time to patients who have not responded well to other treatment options." They should say "to a small minority of patients," but of course that would require integrity, which is not often seen in this industry. And the two-year data that it and the FDA cite do not constitute a long-term benefit, in my opinion.
To make the whole thing even less appealing, Cyberonics admits, "At present, doctors have no way to predict which patients will respond to VNS therapy."
So just put the device in everyone with difficult-to-treat depression, and have the American public pay hundreds of millions of dollars for it: That's what Cyberonics is seeking. For the time being, patients desperate for help are footing the bill.
The company shouldn't expect doctors to "predict which patients will respond." That's its job.
PUBLIC CITIZEN INC. IS PUBICLY DISGUSTED
After extensive investigation, Public Citizen Inc., a nonprofit watchdog group created by Ralph Nader in 1971, submitted testimony to the FDA, characterizing the federal agency's approval of VNS for treatment-resistant depression as "scientifically meritless."
In fact a Senate subcommittee found that one official had overruled all 20 FDA staff members, who had asserted that data submitted by the company did not meet reasonable standards for safety and effectiveness.
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| Ralph Nader: my hero, from the 1960s to forever. |
Public Citizen added that an official involved in the approval process had described it as “very unusual, emotional, not data-driven.”
Public Citizen continued, with rousing conviction: "Even the full-court press of misleading advertising, misleading training sessions in its use for physicians, misleading presentations at the American Psychiatric Association annual meeting, misuse of case managers to help secure reimbursement for individual patients, abuse of FDA employees, misleading clinical trial write-ups, ghost-written review articles and company-generated favorable local media coverage cannot disguise what is lacking and what insurers are increasingly realizing: There are no convincing data of the device’s effectiveness, let alone that it is 'reasonable and necessary'."
(One of the ghost-written journal articles, secretly bought and paid for by Cyberonics, resulted in the forced resignation of its editor, Charles Nemeroff, the chair of Emory University’s Department of Psychiatry and Behavioral Sciences.)
VNS IS A FIRST -- IN A BAD WAY
I have kept tabs on the FDA's controversial, chaotic approval process since my work as a New York consumer advocate in the 1970s. It has given the green light to countless drugs and devices that have turned out to be neither safe nor effective, but these products have always been granted reimbursement status.
Medical devices are held to a significantly lower standard than are pharmaceuticals for reasons I don't understand, particularly since they are appliances that are usually surgically implanted, creating additional risks and costs.
A statement supporting Medicare's denial, published in Current Opinions in Psychiatry, said, "...given the invasive nature of vagal nerve stimulation and potential side effects, further research is urgently required. The scientific evidence is considered to be insufficient to permit conclusions concerning the effect of this technology on major depression."
The insurance industry's position can be summed up thusly: "There is no compelling evidence to support the efficacy of this device or to define the patient population that might be helped by it."
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| The "cuff" that grips the vagus nerve. |
YOU'RE SO VAGUE, YOU PROBABLY THINK THIS TRIAL IS ABOUT YOU
TEC determined, “"Studies examining VNS for the treatment of depression are limited, and all data concerning clinical outcomes come from company-sponsored clinical studies....Given our concerns about the quality of the observational data, these results did not provide strong evidence for the effectiveness of VNS therapy. "
The insurance giant was highly critical of Cyberonics' clinical trials for their limited size and scope. The firm kept reducing the number of patients it promised to include, creating additional skepticism.
"Patient selection was a concern for all of the studies," Blue Cross asserted.
The same studies "have been published in peer-reviewed journals, almost unchanged from the documents (submitted to) the FDA," Blue Cross noted, alluding to the corruption of these journals. "New publications simply analyze the same data in various ways."
Overall, "the available scientific evidence does not demonstrate efficacy of VNS for treatment-resistant depression," Blue Cross concluded, mentioning that "results from the only double-blind trial in a multicenter European study were considered to be inconclusive."
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| I know: It looks like fun. But it's not. |
Aetna's detailed examination of the validity of VNS for depression reached similar results, and it continues to deny reimbursement. "Comparative clinical research(on VNS) is early in its infancy, and many clinical questions about efficacy and effectiveness remain unanswered," Aetna states. "Interpretation of the data is substantially hindered by varying definitions of TRD and the paucity of relevant studies...Even for the few comparisons of treatments that are supported by some evidence, the strength of evidence is low for benefits."
A VAMPIRE LOOKING HUNGRILY AT MY NECK
In many of my blog posts, I have described the callous greed of the health-care industry. Medical-device makers fit right in with this unsavory crowd. Their well-funded lobbying efforts have secured for them a mind-boggling exemption from liability. The "doctrine of pre-emption" relieves them of any financial obligation if one of their devices injures, disables, or kills a patient (http://kronstantinople.blogspot.com/2012/07/heartless.html).
Cyberonics, as the Public Citizen investigation dramatically revealed, is a Bad Boy among bad boys. I am absolutely disgusted that it has been able to continue hawking its fundamentally flawed product to fragile, anguished people who are desperate for relief.
Now the firm is plotting to expand the use of VNS in Alzheimer's disease, anxiety, chronic migraine headaches, and bulimia, even as its reputation is being banged around by scandals that tarnish its credibility in both the stock market and the medical world.
On Nov. 17, 2008, the House Committee on Energy and Commerce launched an investigation into whether senior managers at the Center for Devices and Radiological Health "knowingly corrupted the scientific review process and approved or cleared medical device applications in gross violation" of the law and agency regulations.
According to the National Whistleblowers Center, a substantial matter of CDRH staff dissent had been publicized in 2006 relating to the 2005 pre-marketing approval of Cyberonics' VNS device for treatment-resistant depression. In that case, a Senate Finance Committee investigation, including review of internal documents and interviews with FDA staff, found that Center Director Schultz approved Cyberonics' product after overruling more than 20 FDA staff members, mentioned previously, who had concluded that data submitted by the company did not meet reasonable standards for safety and effectiveness.
(More generally, a 2006 survey of nearly 1,000 FDA scientists found that only 47 percent felt that they could openly express concerns within the agency about public health without fear of retaliation, the Center added.)
The plot thickened as some material provided on the FDA’s website for this device was redacted.
A New Jersey federal court unsealed a complaint in 2012 alleging Cyberonics Inc. violated the False Claims Act in its campaign to convince regulators and doctors that its nerve-stimulating therapy system could treat severe depression, costing states' insurance $75 million, which was spent during the period between FDA approval and CMS rejection.
A MEDICAL COMPANY INFECTED WITH DECEIT
TheStreetSweeper.com, which "uncovers the dirty little secrets every investor needs to know," and is often quoted in the Wall Street Journal, presented an expose by Infinitalis in January 2013 containing "very serious allegations of unscrupulous and potentially fraudulent activity on the part of NASDAQ-listed Cyberonics, Inc."
In its report, TheStreetSweeper presented "the culmination of nearly two months of research into Cyberonics. The more we dug, the more we found red flags and skepticism in the scientific community as to the efficacy of VNS." It linked to 11 research papers, including one in the New England Journal of Medicine, that cast doubt on VNS, and were sourced from academia, government and private enterprise.
"What we found was troubling," TheStreetSweeper reported. "The efficacy of VNS
therapy as measured scientifically in randomized trials was very weak,
and its approval as a treatment was met with unusual controversy."
The article went on to quote award-winning mental health journalist John Mcmanamy's views of the clinical trials. Mcmanamy noted that Cyberonics' president had said that VNS was used on "hopeless, desperate, suicidal patients, not expected to respond."
"Unfortunately, the patients lived up to expectations," Mcmanamy wrote. "Ordinarily, a study with this design and these results never would have made it past the FDA doorman."
The most recent clinical trials didn't change things, except for Cyberonics' stock price.
MARKET REACTION: A PAIN IN THE NECK
A Reuters dispatch on May 28, 2013 reported, "The decision by the U.S. Centers for Medicare and Medicaid Services (CMS) not to provide reimbursement coverage for Cyberonics' Vagus Nerve Stimulation (VNS) therapy sparked a selloff in the company's shares, and dimmed hopes of wider sales of its most important product. Cyberonics stock price plunged 10 percent in extended trade." (Even so, the firm's domestic-product revenues "reached a record high in the last quarter on the back of new patients and higher replacement activity," according to a company press release.)
On the back, indeed. No wonder we have so much back pain in this country. We are hauling around the health-care industry's unconscionable costs, and they just keep going up.
The article went on to quote award-winning mental health journalist John Mcmanamy's views of the clinical trials. Mcmanamy noted that Cyberonics' president had said that VNS was used on "hopeless, desperate, suicidal patients, not expected to respond."
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| Hopeless, desperate, suicidal. I can relate.. |
The most recent clinical trials didn't change things, except for Cyberonics' stock price.
MARKET REACTION: A PAIN IN THE NECK
A Reuters dispatch on May 28, 2013 reported, "The decision by the U.S. Centers for Medicare and Medicaid Services (CMS) not to provide reimbursement coverage for Cyberonics' Vagus Nerve Stimulation (VNS) therapy sparked a selloff in the company's shares, and dimmed hopes of wider sales of its most important product. Cyberonics stock price plunged 10 percent in extended trade." (Even so, the firm's domestic-product revenues "reached a record high in the last quarter on the back of new patients and higher replacement activity," according to a company press release.)
On the back, indeed. No wonder we have so much back pain in this country. We are hauling around the health-care industry's unconscionable costs, and they just keep going up.
CYBERONICS USES PEOPLE, THEN TOSSES THEM ASIDE
As if Cyberonics' bad faith weren't already obvious enough, it flamboyantly announced in 2006 an "unprecedented" lifetime reimbursement guarantee "to honor" hundreds of patients who had participated in its FDA clinical trials and required ongoing care, maintenance and regular replacement of the battery-powered device. By this time, their devices needed to be replaced, and surgeons needed to be paid. Since reimbursement had been denied, these patients -- who had expected that they would be taken care of after volunteering to participate in Cyberonics' studies -- were left holding the bag.
The company promptly got itself a new CEO and reneged on this offer, enraging those who were left with a lifetime of medical bills -- up to hundreds of thousands of dollars for some patients -- that they would have to pay out of pocket. What percentage could not find a way to finance the replacement procedure? No one is saying. I know that second mortgages have been taken out and 401-ks have been ransacked, thanks to Cyberonics' indifference.
When I agreed to participate in the clinical trial, the issue of ongoing care for those who had the device implanted never occurred to me. I guess we all implicitly assumed that study volunteers would be respected -- that they wouldn't just be "thrown under the bus."
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| Cyberonics volunteers became corporate roadkill. |
His flaccid protestations about the weighty problem of helping these patients are appalling, particularly given that Cyberonics is a very profitable firm.
Stein -- a heroically persistent, articulate, forceful and well-informed mental-health advocate -- says his wife and the other study subjects are the victims of a "very stressful and immoral Catch-22."
"We have implanted devices that are therapeutic, with no one willing to care, pay or giving a damn for these patients," Stein told Brown in their email exchange.
Stein's wife, and all the others who responded well to the implant, face a desperate situation: Come up with lots of money every several years, or be plunged back into a life of mental anguish.
One woman wrote to Stein that her VNS battery has died, and
she has been in a deeply hopeless state ever since.
She had her device implanted in the "window" between when VNS was approved by the FDA and CMS determined that it would not provide coverage. Like many of those who have benefited from VNS therapy, she had been so miserable before the implant that she had attempted suicide several times.
Another wrote to Stein: "On Jan 12, 2006 I was implanted with the VNS implant for depression. It was a desperate attempt by my doctor to save my life, which
I had tried to end many times. After the implant was turned on and
adjustments were made, the improvement was almost instantaneous. I will never
forget the day I woke up after the last adjustment and for the first time since
I could remember I thought something is different. Then I knew, I felt
happy, I felt alive, I felt like laughing. My girls came running into the
bedroom because they heard me and we all jumped on the bed wrestling.
Ashley who was 3 said Mommy's back, Mommy's back. And Sara went running
to get her brothers yelling Mommy's all better, look she's all better.
The tears of joy were running down my face and it felt good. Now it is
time for a new generator and I feel the sadness descending. Ashley is 18 and a
senior in high school. She is terrified of losing me again. Sara
says I can see it happening Mom. I come home and you're sleeping just like
when I was little. It's not fair to give children their Mother
back for 7 years and then tell them that's all you get it's over, we're taking
her away again."
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| Beautiful Joyce Stein suffered debilitating depression for 36 years before getting VNS in 1999. |
Cyberonics implanted a device in them that it has no intention of maintaining.
"I have lived in some of the blackest days of my life since my VNS stopped working. The only reason that I have not been hospitalized more is that I no longer believe that it will do any good. I cannot care for my self or even leave my house. My life is very much at stake," another patient told Stein.
One former trial participant poignantly expressed similar anguish: "It's so frustrating, because the stress of the $64,000+ hanging over my head tends to threaten my health and well-being...also the knowledge that I've spent over 18 months jumping thru the hoops required by my insurance company and still have no promise they will pay the bills or cover me in the future for my VNS related services."
Stein has drafted an online petition, which I gladly signed, that would require ongoing care for all study patients in FDA clinical trials. He is expecting a decision soon from CMS on a "compassionate use" exception that would provide funding for those who were implanted with the VNS device and obtained substantial benefit.
Since we obviously can't rely upon corporate America to treat clinical-trial subjects with dignity and fairness, the FDA should impose stringent rules for the protection of patients, who are being grossly exploited under the current regime.
I certainly felt exploited by the process as well, although the cost to me was psychological rather than financial. We who participated were mere cogs in Cyberonics' self-serving machine. We were as dispensable and disposable as Kleenex. It is disgraceful.
Given how few people respond to this extremely expensive treatment, it's not surprising that the scientific community is baffled by FDA approval, and it's certainly not surprising that private and public insurers are refusing reimbursement.
Cyberonics isn't giving up. Company officials seem convinced that if they sustain their lobbying long enough, they will win. If they do, they will have insinuated themselves into one of the most lucrative device markets in the world -- a world filled with very sad people -- and Cyberonics will be very happy. Maybe all the company's Top Dogs will go to Vegas and get their minds blown, no implanted gadget required. Martinis are delicious, especially when they have blondes sitting in them:
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The Cyberonics trials have attempted to prove that the VNS device is effective against refractory, or treatment-resistant, depression.
According to the company's web site, Cyberonics received FDA approval in 1997 "to market VNS therapy for the treatment of epilepsy. Since that time, more than 32,000 patients worldwide have been implanted with the device. The remarkable success of VNS therapy in the treatment of epilepsy has served as a platform for continued innovation."
This is a typical example of the company's deceptive tactics, for which it has repeatedly been criticized. VNS therapy was actually approved for use in a subset of refractory patients, not as a general treatment for epilepsy, and it has not been "a remarkable success."
Patients must continue taking their anti-seizure medications. even after receiving an implant.
The National Institute of Neurological Disorders and Stroke estimates that VNS therapy reduces the frequency of seizures by an average of only 20 to 40 percent in the "small subset" of patients who respond to it.
According to a 2011 meta-analysis in the Journal of Neurosurgery, "disagreement regarding the utility of VNS in epilepsy continues because of the variability in benefit reported across clinical studies. (At best), seizures were reduced by 50 percent or more in approximately 50 percent of the patients. A quarter of patients do not receive any benefit from therapy."
As recently as last month, the American Academy of Neurology referred to ambiguities, evidence gaps and unmet research needs in the use of VNS for refractory epilepsy.
The FDA really makes a mess of things.
Now VNS is being investigated as a possible treatment for heart failure.
On the upside, an August 28, 2013, article in Neurology noted that "a small subset" of patients being treated for epilepsy with VNS experienced an improvement in mood "as an additional benefit."
No wonder Cyberonics confidently plunged into the depression market, which has 10 times as many potential customers.
On July 15, 2005 , after seven years of "extensive study and clinical trials," VNS therapy was approved by the FDA as a long-term adjunctive treatment for treatment-resistant depression.
Cyberonics' trials have been characterized from the start as being too small, poorly designed, sloppily managed and ultimately misleading.
As usual, the most recent trial was guilty of enrolling people who either hadn't met the standards for "treatment resistance" (having failed to get sustained relief from at least four drugs) (it used to be six) (but sometimes it was two), or they were so hopelessly ill that one consultant said, "They are simply lost. Nothing we have can help them."
I don't see how people who are that impaired could even have provided informed consent to participate in this trial, and I am horrified that they were put through it.
One mental-health professional told me that this trial was the most stressful experience of his career. "We were not prepared for the eviscerating impact of coping with such deeply disturbed and inconsolable people," he said. "I never thought I'd say this, but I'm ready to retire."
But this is the extremely depressed population for which VNS claimed to provide a solution.
I was asked to submit to the surgery, even though I suffer from three conditions that should have excluded me, according to Cyberonics' own patient manual.
As I have described, the trial required participants to "bare all" in its intense scrutiny of our psyches, but we were not people in this context -- we were data. Our years of responses to hundreds of questions were merely paperwork, which would form a stack that Cyberonics would point to as "documentation." It was a charade of going through the motions -- from the executive Cyberonics level down to the local clinical trial level -- to amass unwieldy stacks of information that could be tweaked somehow to seduce CMS into changing its mind.
Having suffered from depression and related psychiatric issues for my entire adult life, I was an ideal candidate from Cyberonics' perspective.
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| I was sad. So was my little ego, down below. |
CAUGHT IN A NOOSE, AND I CAN'T GET LOOSE
The VNS appliance is very invasive. The pacemaker-like implant in the chest didn't bother me particularly, but the wire lead, which is firmly attached along the vagus nerve, up the neck, generally can't be removed, no matter what side effects it is producing. The tissues surrounding it become so enmeshed in the lead that it would be life-threatening to extract it, I was told. I couldn't tolerate this.
The thought of having a major component of my central nervous system in the grips of that coil made me feel ill and strangely claustrophobic. I told the study coordinator, "I can imagine freaking out, and trying to rip it out of my neck with my fingernails."
He responded, "That's happened."
Moreover, I was told that I would have to pay $30,000 of my own money to have this controversial, unproven device implanted.
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| What kind of fool do you think I am? |
YOU'VE GOT SOME NERVE
Are you kidding me? People don't pay to be a part of clinical trials -- if anything, they are paid. Cyberonics was conducting the trial for its own financial benefit, yet it expected me to pay for taking a major health risk, and devoting a lot of time subjecting myself to its repeated, probing scrutiny.
Even if data from previous studies had indicated that I had a good chance of experiencing substantial benefit from the implantation of the VNS, I would not have paid. It was their trial, and it was their financial responsibility. But the data were not impressive. Simply put: I was not likely to benefit. No one was -- or is -- likely to, which is why Cyberonics has not been able to get reimbursement status.
The overall failure of VNS to treat refractory depression can overshadow the fact that, for a minority of patients, the device can be "transformative," according to one study coordinator. "In a few cases, it has been quite unbelievable," he said.
My online outreach to those who have had experiences with Cyberonics' clinical trials was very rewarding.
Several people who had been crippled and tortured by depression for many years -- and who had tried everything, including electroconvulsive therapy (ECT) to find relief -- responded in a "miraculous" way to vagus nerve stimulation. It had put them in complete remission, giving them the gift of pleasurable and productive lives.
Mental health activist Herb Stein has sent me several emails from those who have been "saved" by VNS after decades of despair, drugs, job loss, suicide attempts, shock treatments and an inability to function as a parent, spouse or friend. Their stories provide a compelling counterpoint to the hard data, which indicate that VNS is a clinical failure. Here is an example:
"I have suffered from depression for almost 20
years. I have attempted suicide many times. On my best days, I did
not care if I lived or died. Depression has cost me a career as an
accountant, almost destroyed my relationship with my only child, and may still
take my life. I lost 5 years with my daughter because I could not care
for her and I let my ex-husband have custody of her. He told her that I
did not love or want her and I did not get to see her for 5 years. I was first
hospitalized in 1998, then again six more times before October 2006. I
have spent over 83 days in various psychiatric hospitals and have had over 18
ECTs. None of which helped for more than a month at a time. In
October 2006 I was at the very end of my ability to go on. I think God
every day that my doctor told me about VNS therapy. After all I had tried
that failed, I had no hope that VNS therapy would be any different. To my
surprise, after just a few months, I started to feel the crushing weight
of my depression slowly lift. I felt as if my life had been saved.
I have no doubt that I would have been dead within a year if I had not
been lucky enough to get the VNS during the window of opportunity between the
FDA approval and CMS national decision to decline coverage." .
Even many of those who had gotten some relief from VNS had been dismayed, though, at the way in which the studies were conducted. "Unprofessional" is a word that was used a number of times. One man, who worked in administering a trial, described the process as "improvisational," admitting that, "We were flying by the seat of our pants. The whole thing was always on the verge of falling apart. Cyberonics had a slapdash approach."
There were frantic efforts being made, apparently, to find and retain enough patients to constitute a scientifically valid study. The turnover during the trials detracted significantly from their credibility. It was as if Cyberonics had never conducted a clinical trial, and had no idea what it was doing, I was told.
A woman who, like me, was in a control group, said, "I didn't know half the time if it was still being done. No one (at the clinic) seemed to even know if Cyberonics was serious about keeping it going."
I felt the same way. The process seemed haphazard and half-hearted.
AN IMPLANTED DEVICE WITH EMBEDDED SIDE EFFECTS
Given the dire warnings enumerated below, it's easy to see why it was hard to find study participants, despite the fact that there are millions of people in the U.S. with treatment-resistant depression.
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| The whole thing seemed like a pain in the neck. |
The vagus nerve stimulator will alter your body forever. And instead of paying out $20 or $40 dollars to try a drug, you must pay tens of thousands of dollars to have a vagus nerve stimulator implanted. If the device is helping you, and you choose to keep it turned on, you must have it checked regularly, which can cost up to $1,400 per visit. And the device must be surgically replaced every five to seven years, at full price, including costs for doctors, anesthesiologists and surgical center fees. Moreover, VNS is explicitly an "adjunctive" therapy, which means the patient is expected to continue taking pharmaceuticals. This inevitably means side effects on top of side effects.
Possible Surgery or Treatment-Related Problems
Abnormal
dreams
Abnormal thinking
Abnormal thinking
Agitation
Anxiety
Asthma
Belching (eructation)
Chest pain
Choking
Constipation
Constipation
Deafness
Diarrhea
Difficulty sleeping
Difficulty swallowing
Dizziness
Dry mouth
Emotional lability
Eye pain
Fainting (syncope)
Fast heart beat (tachycardia)
Flatulence
Flu syndrome/viral infection
Flushing (vasodilatation)
Gastritis
Headache
Heart palpitations
Heartburn
Hiccup
High blood pressure (hypertension)
Inability
to pass urine
Incision pain (36 percent)
Incision site reaction
Increased appetite
Increased cough (24 percent)
Increased tension of the muscles
Infection at the surgical site
Inflammation
of colon (colitis)
Inflammation of lining in nose (rhinitis)
Inflammation of the throat (pharyngitis)
Joint pain (arthralgia)
Laryngeal inflammation
Loss of memory (amnesia)
Low blood pressure (hypotension)
Low blood pressure upon standing (postural
hypotension)
Migraine
Muscle
ache (myalgia)
Muscle
weakness (myasthenia)
Nausea
Nausea
Neck pain
Nervousness
Numbness
Other reactions around the device generator or leads
Other reactions around the device generator or leads
Pain
Pain around the device generator or leads (29 percent)
Sedation
Shortness of breath (14 percent)
Skin rash
Stoppage of menstrual periods (Amenorrhea)
Tightness in throat
Weight gain/loss
Tingling
(paresthesia)
Tremor
Twitching
Vibrating sound heard during respiration (stridor)
Vocal cord paralysis
Voice alteration (59 percent)
Voice alteration was particularly likely to persist for longer than 90 days. Implantation of the Lead may cause nerve constriction (squeezing of the nerve).Vagus nerve damage, if it occurs, can cause vocal cord paralysis. It can also cause Horner's syndrome. Horner's syndrome has symptoms that involve the eye and eyelid, and an absence of sweating on one side of the face. Nerve damage during surgery may also occur. It could result in permanent hoarseness, difficulty in swallowing, or gastrointestinal problems.
Possible Depression-Related Problems
Appetite change
Concentration problems
Emergence of mania
Fatigue, loss of energy, heavy feeling
Feeling helpless or hopeless or worthless
Feelings of guilt
Feelings of guilt
Feelings of unreality
Sensitivity to how others treat you
Sleep problems
Suicide or thoughts of suicide
Weight
change
Mechanical Problems
Mechanical Problems
The following problems could occur:
The Pulse Generator could malfunction and not deliver stimulation or deliver too
The Pulse Generator could malfunction and not deliver stimulation or deliver too
much stimulation.
The Pulse Generator or Bipolar Lead could move or push through the skin.
The battery in the Pulse Generator could become depleted, (reach its end-of-life).
The Bipolar Lead could break or become corroded, disconnected, or dislodged.
Any mechanical problems could require surgery. Surgery could cause the nerve to swell because of the lead placement around your vagus nerve. If the Pulse Generator and Lead are removed, it is possible the nerve may swell due to the handling of the nerve. Moving the VNS Therapy ™ System could cause damage to the vagus nerve or other parts of your body. You should not move or twist the Pulse Generator or Bipolar Lead.
A malfunction of the Pulse Generator could damage the vagus nerve. This malfunction could lead to permanent hoarseness or other complications. Stimulation may become painful, irregular, or continuous. Call your doctor immediately.
The Pulse Generator or Bipolar Lead could move or push through the skin.
The battery in the Pulse Generator could become depleted, (reach its end-of-life).
The Bipolar Lead could break or become corroded, disconnected, or dislodged.
Any mechanical problems could require surgery. Surgery could cause the nerve to swell because of the lead placement around your vagus nerve. If the Pulse Generator and Lead are removed, it is possible the nerve may swell due to the handling of the nerve. Moving the VNS Therapy ™ System could cause damage to the vagus nerve or other parts of your body. You should not move or twist the Pulse Generator or Bipolar Lead.
A malfunction of the Pulse Generator could damage the vagus nerve. This malfunction could lead to permanent hoarseness or other complications. Stimulation may become painful, irregular, or continuous. Call your doctor immediately.
NO PROBLEMO
I wasn't about to subject myself to the dangers of this unproven device. My role as part of the control group was basically to remain depressed (which Cyberonics could realistically assume I would, after all these years and all those medications). My ongoing depression would magnify any beneficial effects that occurred within the treatment group -- it would skew the data in Cyberonics' favor.
"I despise these companies," I told a study employee.
"All you have to do is get better, if you want to screw things up," he said.
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| (It's not going to happen.) |
WHAT HAPPENS IN VAGUS MAKES ONE NERVOUS
As if all the failures, side-effects and irreversibility of the implant weren't enough, there are quite a few somewhat scary precautions for those who had the device implanted. For example:
"Being close to certain types of equipment can affect the Pulse Generator. Move away from or avoid equipment such as transmitting antennas. Move at least 1.8 meters (6 feet) away from any equipment that interferes with your device. The Cyberonics Magnets are very strong. They can damage televisions, computer disks, credit cards. Move through antitheft devices and medical detectors at a steady pace; do not linger in the area and stay at least 40 centimeters (16 inches) away from such equipment. Electrical or electromechanical devices with a strong static or pulsing magnetic field can cause the Pulse Generator to start suddenly. Such devices may include strong magnets, tablet computers and their covers, hair clippers, vibrators, antitheft tag deactivators, and loudspeakers.
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| Ah, the lucrative beauty of neuromodulation. |
Note that no testing has been done to date. The
effect of radiation on the device is not known. External cardiac defibrillation (an emergency, life-saving procedure) and other procedures for heart problems, as well as extracorporeal
shockwave lithotripsy, diathermy, and electrocautery, may damage the Pulse Generator.
"While the Pulse Generator is stimulating or being set or tested, it may briefly interfere with nearby equipment. If this happens, move at least 1.8 meters (6 feet) away from such equipment. The Pulse Generator can interfere with devices that operate in the 30 kHz to 100 kHz range. Hearing aids and transistor radios operate in this range. The Pulse Generator may affect other implanted medical devices, such as cardiac pacemakers and implantable defibrillators. Possible effects include sensing problems. These could lead to inappropriate responses from the Pulse Generator.
IF YOU HAVE A PULSE, JUST SAY 'NO THANK YOU'
Cyberonics' own clinical trial data are unimpressive when regarded through the eyes of one who needs effective treatment of depression rather than through the eyes of a corporate executive who is fantasizing about an exploding global market. Caveat emptor.
UNPLANTING THE IMPLANTS
Vagus nerve stimulation is being tested by several device makers for possible treatment of a wide array of conditions. But Cyberonics' implanted device may become obsolete before it ever gains a significant foothold in the depression market: Several firms are already developing noninvasive, handheld devices to deliver the electric pulses.
Cyberonics, whose invasive, problematic VNS system has undoubtedly deterred many potential customers -- has seen the light, and has developed an alliance with CerboMed, a private company based in Erlangen, Germany. Its NEMOS t-VNS system, which includes an earplug-like device, is designed to stimulate a branch of the vagus nerve in the outer ear by sending a pulse through the skin.
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| Isn't this a bit nicer than having a wire wrapped deep inside your neck? |
In a clinical trial in Germany, "Five of the seven patients who applied t-VNS for nine months showed a reduction in seizure frequency." This information is obviously not adequate to enable a prospective patient to make an informed decision. How much reduction? How severe was the disease in those studied?
The transcutaneous therapy is also being tested in migraine patients.
Cyberonics’ VNS system already dominates the market in devices for epilepsy. Some 100,000 people worldwide have received its relatively primitive and permanent implant. Think how they must feel, knowing that the wire that is gripping a nerve deep in their necks is unnecessary?
At the 86th congress of the German Society of Neurology in Dresden, CerboMed will present "first-hand information about transcutaneous Vagus Nerve Stimulation (t-VNS)" between September 18 and 21.
COMING NEXT: Neuromodulation is a burgeoning field in the medical-device industry. Profound effects on the brain and body may soon be delivered by high-tech products that are already being tested worldwide. The ambitious medical device firms are already making grandiose problems and hiding mediocre clinical-trial results. They are raising tens of millions of dollars in venture capital. The biggest companies are getting bigger, and the little startups are hoping to attract their attention. Everyone's eyes are on the prize: The pot of gold. Who is watching out for us?
(Today – Oct. 17, 2013 -- the government shutdown has ended, and the medical-device industry, which waged an intense lobbying campaign, says it has garnered enough support to achieve a full repeal of the excise tax by early next year. Medical-device manufacturers allocate only a sliver of profits to research and development The industry’s enormous profits are a result of anticompetitive practices. Exorbitant prices fuel enormous profits — profits that dwarf both the medical-device tax and the industry’s investments in research and development. The United States spends about 50 percent more on the top five medical devices, compared with Europe and Japan, leading to $26 billion annually in excess spending, according to Topher Spiro, vice president for health policy at the Center for American Progress. http://www.nytimes.com/2013/10/17/opinion/the-myth-of-the-medical-device-tax.html?hp&_r=0. )
