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Author Topic: 1997 FDA CDRH Neurological Devices Panel  (Read 10691 times)
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dennis100
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« on: February 10, 2011, 09:55:05 PM »

DR. COSTELLO: Good afternoon, Dr. Wilkinson and members of the panel. This afternoon, I will be discussing issues regarding the safety and effectiveness of the vagus nerve stimulation device......................One-third of the patients had some type of an increase in seizures, with 17 percent having greater than a 25 percent increase.................This slide shows each of the studies and the percent seizure increase. As you can see, in each of the studies, there were patients who had greater than a 100 percent increase. In the E05 study, the range went up to a 234 percent increase, while in the E04 study, it went even higher, to a 680 percent maximum range.

pg. 125
http://www.fda.gov/ohrms/dockets/AC/97/transcpt/3299t1.pdf


DR. PIANTADOSI: Yes; well, one of the things that's concerning me is that the endpoint being measured in all of these studies is, in some sense, a surrogate, counting the number of seizures. I realize that to the patient and to others, it is a very important endpoint, but it may not be as definitive as some other things that we could measure. And there are numerous examples in the methodologic literature about the weaknesses of accepting clinical trial data based on surrogate outcomes, and I would point to, as a recent and a very dramatic example, the cardiac arrhythmia suppression trial, in which the study was designed and the endpoint was selected on the basis of looking at arrhythmias and suppressing them with a drug. And the studies originally seemed to show that the drug was effective in suppressing arrhythmias. The problem was that it was so good in suppressing arrhythmias that it was killing people, and the mechanism was not understood until much later and wasn't even believed until the results of the randomized trial. So, I am very nervous when I see high mortality rates associated with a supposed benefit, even though we don't have a way biologically right now to connect the two. So, that is why I have harped on this this morning and why I am still very nervous with this high death rate. What's your sense of that? I mean, I'm struggling to get some reassurance that my concerns are not well-founded.

Pg. 135
http://www.fda.gov/ohrms/dockets/AC/97/transcpt/3299t1.pdf


DR. PIANTADOSI: Could I just ask the FDA very directly--I'm not confused about what the company thinks, and I really am not interested in the nuances of how SUDEP is defined. Is the FDA satisfied that this device is not associated with an elevated risk of death, all-cause mortality, whatever you want?

DR. COSTELLO:............So, to answer your question, I don't believe it has been shown that the high death rate is directly related to the device. However, we only have 2,000 patient years of experience and a limited number of patients...............I cannot say that I believe that there is an increased risk right now, but I would not want to rule it out either. I think that would require a longer-term study.

Pg. 142
http://www.fda.gov/ohrms/dockets/AC/97/transcpt/3299t1.pdf

The VNS was approved 19 days after this panel met.

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« Reply #1 on: February 10, 2011, 09:56:05 PM »

DR. DUFFELL: Because it has come up twice. I just want to make sure--I don't know that I was perfectly clear. The output current, I understand your concern, both of you. You have to realize that it is a rate limiting phenomenon by the patient himself. I think any of the doctors here would tell you: since this device is going on and off every 5 minutes, if they can't tolerate it, they won't leave. You know, they only go to the level of perceptibility and comfortable tolerance. You would never have an instance where a patient went home and, all of a sudden, should have a reaction to an output current, because they will have seen it before they left the office.

Pg. 185
http://www.fda.gov/ohrms/dockets/AC/97/transcpt/3299t1.pdf
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« Reply #2 on: February 10, 2011, 09:57:09 PM »

DR. CANADY: You mentioned in your presentation just now that in looking at the EEG results of humans that you didn't see any changes. Is there any electrophysiological data, either by telemetry or Holter monitoring of anything other than self-reported seizure frequency?

DR. NARITOKU: I think the question arises whether they are by visual analysis or by spectral analysis, and I think the person probably best to answer it is Dr. Salinsky,who has actually done the studies on EEG. May I refer it to him?

DR. SALINSKY: We performed a study during the E03 protocol looking at spectral analysis of EEG segments before the stimulator was turned on, during stimulation and then after stimulation, so, this was not a chronic experiment; it was strictly an acute experiment in patients using the device. We looked at, I believe, six patients. We did not see any significant changes in background EEG. Now, this was not ictal EEG; this was background EEG. There have been other reports, specifically from Dr. Uthman's group--I think he's here as well--and Dr. Hammond looking at EEG by visual inspection, and again, there do not appear to be any changes in the background EEG pattern. Nobody has yet investigated whether there are any specific changes in an ictal EEG pattern in humans. That would be, obviously, much more difficult to do.

Pg. 78
http://www.fda.gov/ohrms/dockets/AC/97/transcpt/3299t1.pdf



* Investigating whether there are any changes to an ictal EEG pattern during VNS stimulation would not be "difficult to do." As a matter of fact it would be very easy. Video-EEG is the way to do it. When the patient feels an aura they use the magnet to swipe the device and Wah-Lah - You have captured a seizure on EEG while the device is stimulating.


FYI-An aura is a simple partial seizure
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« Reply #3 on: February 10, 2011, 09:59:04 PM »

DR. SNEAD: I think that's a reasonable suggestion. I would like to just say a word of caution about including children at this date. First of all, I am not convinced that we have data to do that. Secondly, what we have heard about today are that the patients will tell you when the stimulus is too high, because they are uncomfortable, because of the voice change. Well, some children are not able to do that, and some children are severely neurologically handicapped; some children are too young, and you really need to be very careful about extrapolating these data into that kind of population.

DR. WILKINSON: Any other comment, then, about this question?

DR. SPYKER: I'm not sure I understood the suggestion. We already have it back in the has not been shown effective. That's on page 12, and I guess, well, so,the question stands: do we want to leave this in the indication section. I don't propose that we remove it from back in individualization of treatment?

DR. WILKINSON: It's already in that paragraph.

DR. SPYKER: Yes, sir. Thank you.

DR. WILKINSON: Yes. So, leaving it in this paragraph would emphasize the lack of data for the 12-year-old age cutoff, but not listing it as an absolute contraindication would still leave the clinician some leeway, so, perhaps leaving this in does make sense.

DR. DUFFELL: Could I make a comment on that?

DR. WILKINSON: One quick comment.

DR. DUFFELL: I agree with what you're saying, but what we also need to remember is that what the indications state also greatly influences what the payers will pay for. So, the panel needs to consider that as well. We will work with the FDA to constructively work out whatever the label should be, but I wouldn't want you to neglect that in your considerations as well.

DR. WILKINSON: And also, the future will come, and with the future may come data.

[Laughter.]


pg. 201
http://www.fda.gov/ohrms/dockets/AC/97/transcpt/3299t1.pdf


Dr. Wilkinson - Committee Chairman

Dr. Snead - Committee voting member

Dr. Spyker - FDA

Dr. Duffell - Cyberonics
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« Reply #4 on: February 10, 2011, 10:00:52 PM »

DR. REID: Thank you, Dr. Duffell, Chairman Wilkinson, distinguished members of the panel. I appreciate the opportunity to make this presentation to you today. I have no financial interest in the Cyberonics Corporation,but they did pay my way to come here to speak to you.

The procedure is performed for selected patients after routine presurgical evaluations. The NeuroCybernetic Prosthesis provides an additional tool for the neurosurgeon in his armamentarium against epilepsy. The entire patient system is implanted, with no transcutaneous leads, and so, patients can, therefore, participate in athletics and other activities unrestricted. The procedure has been done by neurosurgeons, vascular surgeons and other surgeons familiar with surgery within the carotid sheath. The NCP system implantation is fully reversible surgically ..................

Hoarseness, persistent, not related to the stimulation, occurs in approximately 1 percent of the patients and should be followed with immediate laryngoscopy and removal of the lead if the vocal cord is noted to be paralyzed; otherwise, it usually recovers.

pg. 49
http://www.fda.gov/ohrms/dockets/AC/97/transcpt/3299t1.pdf
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« Reply #5 on: February 10, 2011, 10:06:38 PM »

DR. DUFFELL: I mean, I can comment briefly before Marty makes his statement that, I mean, certainly the intent of the company to make sure that the individuals who implant and treat with the device are adequately trained, and one of the things that we are striving and working with the agency over the labelling is to make sure that the labelling, of course, very appropriately says what the device is and is not capable of doing so that the expectations will be right. We're not interested in seeing this thing prescribed like aspirin for the treatment of epilepsy. It would be counterproductive to our commercial success years from now to have that happen.

Pg 101
http://www.fda.gov/ohrms/dockets/AC/97/transcpt/3299t1.pdf
______________________________________________________________


Model Number 102
Event Date 11/01/2002
Event Type Injury Patient Outcome Life Threatening;
Manufacturer Narrative
Report is incomplete because attempt to obtain additional information has been unsuccessful to date.
Event Description
Patient has had an increase in seizures since their implant. The patient had been having 1 seizure every month or every other month and is now having 2-3 seizures a month.

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfmaude/detail.cfm?mdrFOI__ID=448108


Event Date 01/01/2003
Event Type Injury Patient Outcome Life Threatening;
Event Description
Reporter indicated that the pt had experienced a total of 13 seizures the year prior and that pt had only experienced a total of 5 seizures 3 years before, prior to being implanted with vns therapy system.

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfmaude/detail.cfm?mdrFOI__ID=550791


Model Number 102
Event Date 10/01/2003
Event Type Injury Patient Outcome Life Threatening; Required Intervention
Event Description
Reporter indicated that vns pt had experienced an increase in seizures since stimulation was initital. It was reported that pre-vns implant, the pt had one seizure per year. The pt has had approximately one seizure per week since initiation of vns therapy and that there had been no recent changes to their drug regimen. Further follow-up revealed that treating neurologist plans to increase vns settings and possibly decrease anti-epileptic medications. Neurologist indicated that the relationship between the vns therapy system and the reported event was unknown. The pt is still with increased seizures.

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfmaude/detail.cfm?mdrFOI__ID=508838


Model Number 102
Event Date 03/01/2004
Event Type Injury Patient Outcome Life Threatening;
Event Description
Reporter indicated that pt has recently experienced an increase in seizures. It was reported that the pt experienced 1-2 seizures per year prior to vns implant and that pt recently experienced 3 seizures within one month. Treating neurologist indicated that the pt was doing fine and that the reported event was not related to the vns. The pt's seizures types had not changed. The pt's health condition is reportedly not worsening and there were no environmetal stimuli that may have contributed to the increase in seizure activity. Neurologist indicated that programming the pt's device to off resulted in no change to the pt's condition or symptoms.

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfmaude/detail.cfm?mdrFOI__ID=522645


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« Reply #6 on: January 16, 2012, 02:19:59 PM »

Compare Dr. Naritoku's patent file date to the neurological devices panel date.

Dr. Naritoku's
U.S. PATENT
 
Methods of treating traumatic brain injury by vagus nerve stimulation

Filed May 30, 1997 - Issued Aug 15, 2000

http://www.google.com/patents?id=nXoEAAAAEBAJ&printsec=frontcover&dq=Dean+Naritoku&hl=en&sa=X&ei=uh8VT4PBHKrO2wWwtr2ECg&ved=0CD0Q6AEwAw



1997 FDA CDRH Neurological Devices Panel

Friday, June 27, 1997
 
DR. NARITOKU: Mr. Chairman and panel, thank you for inviting me to speak. My name is Dean Naritoku. I am an associate professor of neurology and pharmacology at the Southern Illinois University School of Medicine in Springfield, Illinois. I have been an investigator in both the E03 and E05 studies and have been a consultant for Cyberonics. Otherwise, I do not have a financial interest in the company, and my travel was also covered by Cyberonics.

pg. 72

http://www.fda.gov/ohrms/dockets/AC/97/transcpt/3299t1.pdf


Dean Naritoku, M.D.
 
GRANTS
Laboratory Research Funding - Principal Investigator
 
Prior to 1997
 
Cyberonics, Inc: Vagus Nerve Stimulation for Intractable Partial Epilepsy. $84,586; 11/90-1992.
 
Cyberonics, Inc: Functional Anatomy of Vagus Nerve Stimulation. $25,000. 7/1/93 - 6/30/94.
 
Cyberonics, Inc.: E05: Assessment of vagus nerve stimulation (VNS) for adjunctive treatment of epilepsy patients who have refractory partial onset seizures with alteration of consciousness. $189,875; 4/95-3/97.
 
Cyberonics, Inc.: XE5: Open-Label Treatment of Refractory Partial Onset Seizures Using Vagus Nerve Stimulation. Principal Investigator - Dean K. Naritoku, M.D. ; $30,000 11/95 - 8/97
 
Cyberonics, Inc: "Studies on the role of brain monoamines in the anticonvulsant effect of vagus nerve stimulation (VNS)." (co-principle investigator with R. Browning) $9094; 7/1/95-6/30/97.
 
total  $329,461
 

Funding as co-investigator
 
Cyberonics: "Studies on the enhancement of memory storage processed by vagus nerve stimulation (VNS)." Principle investigators: R. Jensen; $16,659; 7/1/95-6/30/95.
 
 
after 97'
 
Cyberonics, Inc. "An investigation of the capacity of vagus nerve stimulation to alter the course of recovery of function from brain damage in laboratory rats." (Douglas Smith and Robert A. Jenson, co-principal investigators) $40,000. 7/14/98-7/13/00.
 
http://www.minifellow.net/Naritoku.html
 
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« Reply #7 on: January 16, 2012, 07:33:38 PM »

Others from the patent office with Dr. Naritoku's name.


Apparatus and method for adjunct (add-on) therapy of partial ...
Filed Oct 26, 1998 - Issued Mar 20, 2001


Overview

An apparatus and method for adjunct (add-on) therapy of partial complex epilepsy, generalized epilepsy and involuntary movement disorders comprises an implantable lead-receiver, an external stimulator having controlling circuitry and a power source, and an electrode to inductively couple the stimulator to the lead-receiver. The external stimulator emits electrical pulses to stimulate a cranial nerve such as the left vagus nerve according to a predetermined program. In a second mode of operation, an operator may manually override the predetermined sequence of stimulation.

http://www.google.com/patents?id=EkAGAAAAEBAJ&pg=PA2&dq=Dean+Naritoku&hl=en&sa=X&ei=KCEVT4WPH-HK2AXcxcyDCg&ved=0CDEQ6AEwADgK


Apparatus and method for adjunct (add-on) therapy of Dementia and ...
Filed Oct 26, 1998 - Issued Jul 31, 2001


Overview

An apparatus and method for adjunct (add-on) therapy of dementia and Alzheimer's disease comprises an implantable lead-receiver, an external stimulator having controlling circuitry and a power source, and an electrode to inductively couple the stimulator to the lead-receiver. The external stimulator emits electrical pulses to stimulate a cranial nerve such as the left vagus nerve according to a predetermined program selected from at least two predetermined programs.


http://www.google.com/patents?id=jXIIAAAAEBAJ&pg=PA2&dq=Dean+Naritoku&hl=en&sa=X&ei=KCEVT4WPH-HK2AXcxcyDCg&ved=0CDQQ6AEwATgK


Apparatus and method for adjunct (add-on) therapy for pain ...
Filed Oct 26, 1998 - Issued Mar 27, 2001


Overview

An apparatus and method for adjunct (add-on) therapy of painful syndromes comprises an implantable lead-receiver, an external stimulator having controlling circuitry and a power source, and an coil to inductively couple the stimulator to the lead-receiver. The external patch contains means for compensating for the change in axis of external transmitting and internal receiving coils. The external stimulator emits electrical pulses to stimulate a cranial nerve such as the left vagus nerve according to a predetermined program. The pre-determined programs include both short term and long term stimulation.

http://www.google.com/patents?id=JqoGAAAAEBAJ&pg=PA2&dq=Dean+Naritoku&hl=en&sa=X&ei=KCEVT4WPH-HK2AXcxcyDCg&ved=0CDcQ6AEwAjgK


Methods of modulating aspects of brain neural plasticity by vagus ...
Filed Jul 10, 2000 - Issued Jan 15, 2002



Overview

Methods of modulating brain neural plasticity, improving memory and learning, improving recovery from traumatic brain injury, preventing epilepsy, treating memory disorders and chronic memory impairment, and treating persistent impairment of consciousness in humans and animals by vagus nerve stimulation are provided. These methods comprise selecting an appropriate human or animal subject and applying to the subject's vagus nerve an electrical stimulation signal having parameter values effective in modulating the electrical activity of the vagus nerve in a manner so as to modulate the activity of preselected portions of the brain.


http://www.google.com/patents?id=__MKAAAAEBAJ&printsec=frontcover&dq=Dean+Naritoku&hl=en&sa=X&ei=giEVT5e8DcjK2AWWvrWECg&ved=0CDUQ6AEwAQ



Method and system for spinal cord stimulation prior to and during ...
Filed Sep 26, 2000 - Issued Nov 26, 2002


Overview

A method of performing a medical procedure, such as surgery, is provided. The spinal cord is stimulated in order to control at least one physiological function. The medical procedure is performed and stimulation of the spinal cord is stopped.

http://www.google.com/patents?id=N6ALAAAAEBAJ&pg=PA2&dq=Dean+Naritoku&hl=en&sa=X&ei=giEVT5e8DcjK2AWWvrWECg&ved=0CEEQ6AEwBQ


Method and system for nerve stimulation prior to and during a ...
Filed Sep 26, 2000 - Issued Sep 10, 2002


Overview

A method of performing a medical procedure, such as surgery, is provided. A nerve is stimulated in order to adjust the beating of the heart to a first condition, such as a stopped or slowed condition. The medical procedure is performed on the heart or another organ. The stimulation of the nerve is stopped in order to adjust the beating of the heart to a second condition, such as a beating condition. The heart itself may also be stimulated to a beating condition, such as by pacing. The stimulation of the nerve may be continued in order to allow the medical procedure to be continued. Systems and devices for performing the medical procedure are also provided.

http://www.google.com/patents?id=BLsLAAAAEBAJ&pg=PA2&dq=Dean+Naritoku&hl=en&sa=X&ei=giEVT5e8DcjK2AWWvrWECg&ved=0CEQQ6AEwBg


Method and system for endotracheal/esophageal stimulation prior to ...
Filed Sep 26, 2000 - Issued Mar 11, 2003


Overview

A method of performing a medical procedure, such as surgery, is provided. A nerve is stimulated to adjust the beating of the heart to a first condition, such as a stopped or slowed condition. The medical procedure is performed on the heart or another organ. The stimulation of the nerve is stopped to adjust the beating of the heart to a second condition, such as a beating condition. The heart itself may also be stimulated to a beating condition, such as by pacing. The stimulation of the nerve may be continued to allow the medical procedure to be continued. Systems and devices for performing the medical procedure are also provided.

http://www.google.com/patents?id=fMoOAAAAEBAJ&pg=PA2&dq=Dean+Naritoku&hl=en&sa=X&ei=giEVT5e8DcjK2AWWvrWECg&ved=0CEcQ6AEwBw

Methods for improving learning or memory by vagus nerve stimulation
Filed Jan 14, 2002


Overview

Methods of improving memory and learning in humans and animals by vagus nerve stimulation are provided. These methods comprise selecting an appropriate human or animal subject and applying to the subject's vagus nerve an electrical stimulation signal having parameter values effective in modulating the electrical activity of the vagus nerve in a manner so as to modulate the activity of preselected portions of the brain.

http://www.google.com/patents?id=DC2RAAAAEBAJ&printsec=frontcover&dq=Dean+Naritoku&hl=en&sa=X&ei=giEVT5e8DcjK2AWWvrWECg&ved=0CDIQ6AEwAA

Methods of treating persistent impairment of consciousness by ...
Filed Jan 14, 2002


Overview

)Methods of treating persistent impairment of consciousness in humans and animals by vagus nerve stimulation are provided. These methods comprise selecting an appropriate human or animal subject and applying to the subject's vagus nerve an electrical stimulation signal having parameter values effective in modulating the electrical activity of the vagus nerve in a manner so as to modulate the activity of preselected portions of the brain.

http://www.google.com/patents?id=Cy2RAAAAEBAJ&printsec=frontcover&dq=Dean+Naritoku&hl=en&sa=X&ei=giEVT5e8DcjK2AWWvrWECg&ved=0CDgQ6AEwAg

Method and system for nerve stimulation and cardiac sensing prior ...
Filed Dec 1, 2003 - Issued May 29, 2007


Overview

A method of performing a medical procedure is provided. The medical procedure includes stimulation of a patient's heart while stimulating a nerve of the patient in order to modulate the patient's inflammatory process. More particularly, the medical procedure includes pacing the ventricles of the patient's heart while stimulating the vagal nerve of the patient. Systems and devices for performing the medical procedure are also provided.


http://www.google.com/patents?id=OR6AAAAAEBAJ&pg=PA3&dq=Dean+Naritoku&hl=en&sa=X&ei=giEVT5e8DcjK2AWWvrWECg&ved=0CEoQ6AEwCA



ELECTRICAL AND MAGNETIC STIMULATORS USED TO TREAT MIGRAINE/SINUS ...
Filed May 17, 2011


Overview

Non-invasive electrical nerve stimulation devices and magnetic stimulation devices are disclosed, along with methods of treating medical disorders using energy that is delivered noninvasively by such devices. The disorders comprise migraine and other primary headaches such as cluster headaches, including sinus symptoms that resemble an immune-mediated response (“sinus” headaches), irrespective of whether those symptoms arise from an allergy that is co-morbid with the headache. The disclosed methods may also be used to treat other disorders that may be co-morbid with migraine headaches, such as anxiety disorders. In preferred embodiments of the disclosed methods, one or both of the patient's vagus nerves are stimulated non-invasively. In other embodiments, parts of the sympathetic nervous system and/or the adrenal glands are stimulated.

http://www.google.com/patents?id=8hHxAQAAEBAJ&pg=PA34&dq=Dean+Naritoku&hl=en&sa=X&ei=fyIVT7OVJ8ng2QXmsYiDCg&ved=0CDoQ6AEwAzgK

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« Reply #8 on: January 18, 2012, 01:19:30 PM »

Good morning, everyone. My name is Paulette Machara, and I'm the chief executive officer for the Epilepsy Foundation of America, and I very much appreciate the opportunity to appear here today on behalf of individuals with epilepsy who may benefit from the new implantable electrical stimulator, the  euroCybernetic Prosthesis.We hope that your review of the NCP system will find it safe and an effective device. We are excited about the possibilities that the NCP system represents, since it is the first device treatment option for epilepsy. The Epilepsy Foundation of America is the national organization that works for people affected by seizures and epilepsy through research, education, advocacy and service. Together with our 66 local affiliates, we monitor developments in the medical management of seizures and epilepsy very closely.


Approximately 2.5 million Americans of all ages have epilepsy. Of those, it is estimated that nearly one in three continue to have seizures that are not completely controlled with current available therapies. This leads to a diminished quality of life. In addition, for some, seizures are frequent and severe and can be life-threatening. In fact, status epilepticus, or a prolonged seizure, is potentially life-threatening, causing some 22,000 to 42,000 deaths per year, according to a recent community-based study.
 

Now, if you want to compare that to other popular causes today of diabetes, for instance, 48,000 deaths; female breast cancer, 43,000 deaths and AIDS at 29,000 deaths, this clearly is a very serious disease or disorder.We receive some 30,000 calls a year to our toll-free service, often from families that are desperate for new solutions to their unresolved problems. The recent television movie First Do No Harm brought thousands of calls alone by adults and family members who were wanting more information about the ketogenic diet and its use in adults.


Uncontrolled epilepsy can cause considerable psychological, sociological and financial stress on individuals and families living with epilepsy. Living with the unpredictability of partially-controlled or uncontrolled seizures takes a toll on the individual and the family. Studies have shown increased dependence and lack of self-esteem can develop in children with epilepsy.


Continuing to have seizures results in a loss of driving privileges, which impacts mobility and can affect employment options for people with epilepsy. Unemployment and underemployment remain important concerns to youth and adults with seizure. Intractable epilepsy remains a very serious health problem.


As I mentioned earlier, current treatment options do not work for all individuals with epilepsy. Side effects of many of the current available medications can be quite disabling in some individuals and may adversely impact cognition and memory. Women of childbearing age have additional concerns. Many commonly-used antiepileptic drugs are human teratogens, yet most women with epilepsy must be treated throughout pregnancy in order to be protected against the adverse maternal and fetal effects of seizures. Maternal seizures may pose significant risk to mothers and the fetus. We cannot always predict which women will experience an increase in seizures during pregnancy.


The NCP system may be a unique opportunity for people with epilepsy. It does represent the first time a device has been developed to minimize or prevent seizure activity. If it can reduce seizure frequency and reduce the number of medications that an individual must use, people with epilepsy will benefit. It also offers patients self-management aspects, which are so critical to people with epilepsy.


The Epilepsy Foundation of America views it as a part of our mission to have individuals with epilepsy be advocates on legislative and regulatory policies that will affect their lives. Thus, we have asked individuals like Tim who have had an experience with this product to come forward and share their stories with you. We have paid for their travel and accommodations so that they can be here to talk to you personally this morning. But they are not serving as official spokespersons for the Epilepsy Foundation of America.


While the experiences that they describe today are generally positive, we recognize from the research that others have not experienced such dramatic reductions in their seizures. As you will hear, the NCP system is a positive development in the treatment of seizures. We believe that individuals with epilepsy are in the best position to speak of the impact of this product and their quality of life and how a reduction in seizure frequency can make a difference in employability, self confidence and overall wellbeing.


We recognize that this device is not a cure for epilepsy. It will not help everyone who implants the system, and we urge the company to continue their research on the device and other possible applications in individuals with epilepsy to more precisely identify who may be helped with this system. The Epilepsy Foundation of America does not endorse this product or any other treatment option for epilepsy. We rely on the FDA and the advisory committee to conduct a thorough review and make recommendations on the safety and efficacy of all treatments.


At the same time, we encourage rapid review of new drugs or devices, especially those designed to meet unmet needs. People with epilepsy will benefit from more frequent treatment options if they are adequately informed about the full extent of these options. We very much appreciate the opportunity to make comments about the NCP system, and I would just like to leave you with our disclosure statement: The Epilepsy Foundation of America is a public charity. We solicit contributions from the general public, including corporations. We have periodically received donations from Cyberonics since 1993. We welcome these contributions to the cause of epilepsy and to the support of our work.


All EFA policy positions are developed independently and adhere to strict ethical principles and conflict of interest practices. As a matter of policy and practice, the Board of Directors of the Epilepsy Foundation of America who have a conflict of interest in a particular matter do not participate in that discussion or voting on that issue. And I would be happy to answer any questions that you might have.


Thank you.


DR. WILKINSON: Thank you, Ms. Machara.

Any questions from the panel?


[No response.]





pg. 16
http://www.fda.gov/ohrms/dockets/AC/97/transcpt/3299t1.pdf



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« Reply #9 on: May 28, 2012, 02:11:37 PM »

In contrast, the E05 study had a statistically significant change only in the mean percent change. The median percent change and the number of patients who had greater than a 50 percent response was not statistically significantly different between the high and the low groups.


In addition, the E03 study stimulated patients every 90 minutes, as compared to the E05 study, where patients were stimulated every 180 minutes. The sponsor this morning has discussed reasons why the E03 group potentially was so low, and using the inclusion/exclusion criteria of the E05 study, did result in approximately a 15 percent reduction. However, if you examine this data from a type of dose-response in terms of 90 minutes versus 180 minutes, we would still expect a lower value in the E05 group relative to the E03 group.


In terms of the open-label E04 study, the mean percent change was not significantly different. It was only a 7 percent change, while the median percent change and the greater than 50 percent responder rate was statistically improved.


pg. 128
http://www.fda.gov/ohrms/dockets/AC/97/transcpt/3299t1.pdf
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« Reply #10 on: May 28, 2012, 02:14:00 PM »

The next issue which I would like to address is the long-term data. As can be seen in the extension phase
of the XE5 study, here are the results of the randomized, controlled trial and then followup at 4, 6 and 9 months. Both the mean percent change and the median percent change during the extension phase showed approximately a 30 percent seizure reduction for these patients. However, this data is confounded by the fact that the patients were changing their medications during this period.


Similarly, despite optimal antiepileptic drug therapy, only 20 percent of the patients in the extension phase, using a last visit carried forward analysis, had 50 percent or greater reduction in seizures. One-third of the patients had some type of an increase in seizures, with 17 percent having greater than a 25 percent increase.


pg. 130
http://www.fda.gov/ohrms/dockets/AC/97/transcpt/3299t1.pdf

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« Reply #11 on: July 02, 2012, 01:53:13 AM »

DR. COSTELLO: Good afternoon, Dr. Wilkinson and members of the panel. This afternoon, I will be discussing issues regarding the safety and effectiveness of the vagus nerve stimulation device......................One-third of the patients had some type of an increase in seizures, with 17 percent having greater than a 25 percent increase.................This slide shows each of the studies and the percent seizure increase. As you can see, in each of the studies, there were patients who had greater than a 100 percent increase. In the E05 study, the range went up to a 234 percent increase, while in the E04 study, it went even higher, to a 680 percent maximum range.

pg. 125
http://www.fda.gov/ohrms/dockets/AC/97/transcpt/3299t1.pdf

What kind of idiot would approve a medical device that actually worsens the condition in 33% of it's recipients ? There has to be a reason the FDA approved it and It certainly wasn't to control epilepsy. "First do no harm" is the Physician's motto. Well you folks at the FDA have done plenty of harm. 1,800 "REPORTED" vns deaths and 17,000 "REPORTED" adverse events. If anyone at the FDA were able to count they would see with out question something is amiss here. 80,000 or so registered devices and all these "REPORTED" problems and deaths is just sickening, just sickening.

Dr. Maisel (FDA) Would you allow any of your loved ones to have this device implanted into their chests? Better yet would you have one?


Make your voices heard and don't stop until this device is removed from the market and those responsible for approving it are criminally charged.

FDA Commissioner
Dr. Margaret A. Hamburg
margaret.hamburg@fda.hhs.gov

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« Last Edit: August 20, 2012, 04:07:51 PM by dennis100 » Logged
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« Reply #12 on: April 14, 2014, 03:12:59 AM »

With 1/3 of premarket study patients experiencing an increase in seizures the VNS should never have even been considered for approval.

DR. COSTELLO: Good afternoon, Dr. Wilkinson and members of the panel. This afternoon, I will be discussing issues regarding the safety and effectiveness of the vagus nerve stimulation device......................One-third of the patients had some type of an increase in seizures, with 17 percent having greater than a 25 percent increase.................This slide shows each of the studies and the percent seizure increase. As you can see, in each of the studies, there were patients who had greater than a 100 percent increase. In the E05 study, the range went up to a 234 percent increase, while in the E04 study, it went even higher, to a 680 percent maximum range.

pg. 125
http://www.fda.gov/ohrms/dockets/AC/97/transcpt/3299t1.pdf
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