Patient Representative: Perry D. Cohen, Ph.D.

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CHAIRPERSON CANADY:  Dr. Cohen.
  DR. COHEN:  Yes, I have a few questions about how this technology might be applied to patients.  One has to do with the qualifications and training of the physicians that would do this implantation.  And Dr. Lozano, I believe, mentioned earlier that the Stereotactic Society does training or, my question is, is there any kind of certification mechanism that would get this society, professional societies could do to assure patients that they were getting well trained physicians?
  And second of all, earlier Mr. Elliott in his presentation said that the professional associations provided information to patients.  Would professional associations provide that information on who was trained or what kind of training they had?  And with, another, maybe you could answer and then I could ask the other question?
  MS. PRITCHARD:  I'll have Dr. Lozano address your issues.
  DR. LOZANO:  So this is an important issue.  With respect to these associations, I can think of two examples where associations or organized medicine have taken initiatives to try to address this issue.  One is to publish guidelines.  So for example recently several Neurologists and Neurosurgeons were involved in the assessment of surgical procedures for Parkinson's Disease in general.  And this was done, a therapeutic assessment with the Academy of Neurology and there was an assessment of surgical procedures with guidelines as to what procedure should be done and how they should be done, what kind should be done.
  So that's one initiative.  Another initiative is within the neurosurgical stereotactic and functional neurosurgical community and the American Society.  We have also, are working on guidelines for doing these procedures, what are the requirements that we recommend as a Society for doing these procedures.  So these will be guidelines that will be published and available.
  We don't have a policing function, but we simply establish these guidelines and say this is what we recommend.
  DR. COHEN:  Do you have an certification mechanism?
  DR. LOZANO:  No, there is no certification.  The certification is just you are a neurosurgeon, that is a certification.  You are certified as a neurosurgeon, within that you, you do whatever procedures you feel you are competent in doing.
  DR. COHEN:  As a patient, I wouldn't want somebody operating on me after they watched a videotape.  And do any of the professional, the patient association provide this kind of information?
  DR. LOZANO:  No, I agree with you.  We want these procedures to be done by experienced Centers, by people that are qualified.  And you know, it's our job to ensure that that training is available and that patients have access to Centers that have the training and experience to do these procedures.
  CHAIRPERSON CANADY:  I'm going to ask for one more question.  I would remind people that there will be an opportunity for these discussions later as well, this isn't the only shot.
  DR. COHEN:  Can I ask one last question?
  CHAIRPERSON CANADY:  Okay, Dr. Cohen.
  DR. COHEN:  This is on a different issue.
  CHAIRPERSON CANADY:  I'd rather wait on a different issue until later, if we could.
  DR. COHEN:  Okay.

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  CHAIRPERSON CANADY:  Dr. Cohen?
  DR. COHEN:  I have a general question about patient selection.  I was going to ask this earlier, but I think it's very pertinent now.  On what types of patients are you recommending this treatment be used for and are there some objective criteria or even professional judgment criteria by which you could determine a patient that would benefit from this treatment versus a patient that wouldn't be recommended for this treatment and what proportion of patients do you think that represents?
  MS. PRITCHARD:  I would ask Dr. Vitek to respond.
  DR. VITEK:  Basically, my feeling about this and I think everybody else would agree with me was involved in a study in doing this work right now is that patients with idiopathic Parkinson's, with a clear diagnosis of Parkinson's disease with a history of responsiveness to levodopa and even those patients who were advanced and have lost their response, where it's unpredictable, but they even get a minute or five minutes in a day where they get a response to medication and their balance may improve or their freezing improves, then I think these are patients for deep-brain stimulation because we have seen that those patients can definitely respond to stim even though they may have a very unpredictable response to medication, so those are the patients that I would consider and I personally would consider either target for patients with midline symptoms, who have freezing, balance problems, the numbers themselves do not differ that much, but the number of patients that were enrolled in each target do differ and so you'll see patients who respond very well with DBI stim and some patients who may not respond that well.  And you'll see the same thing with STM.
  DR. COHEN:  And the question was raised by the previous speaker this comparing this treatment to as a general purpose treatment and from what I understand you're not recommending, are you not, seeking approval for a general purpose treatment, but it's only for a select group of patients?
  DR. VITEK:  What we have studied are patients with advanced Parkinson's who are at the point where medical therapy is no longer effectively controlling their symptoms.
  DR. COHEN:  So the medical therapy is not an acceptable comparison?
  DR. VITEK:  These patients were all on medical therapy and were at a point, basically, where they were no longer able to be controlled with medical therapy so they had a lot off time.  They had motor fluctuations.  When they were on they were dyskinetic, very unpredictable responses as I said.  Those are the kinds of patients that were studied here and these types of patients are at the end of their rope, so they have no other alternatives.  Their options are gone.
  DR. COHEN:  And what proportion of patients are included in this category?
  DR. VITEK:  What proportion of patients in the whole population of Parkinson's patients?
  DR. COHEN:  Yes.
  DR. VITEK:  That are diagnoses?
  DR. COHEN:  Uh-huh.
  DR. VITEK:  Anybody else?  What do you think the numbers would be.  Thirty or 40 percent, that high?
  Our feeling is that if you take the total population of Parkinson's patients and go over their whole history, then certainly by the time -- if you take all the patients, let them go over time, probably 30 percent of that population is what I would feel will get to a point where they're going to be in this position and I think that's conservative.  Some of my colleagues may think that's not, but I think it is.
  DR. COHEN:  But at any one time --
  DR. VITEK:  I don't know if I can comment on any one point in time what number of patients are out there that would need this therapy.
  DR. COHEN:  Okay.
  DR. VITEK:  I can tell you that of all the patients that have Parkinson's disease, at least I would think 30 percent of those patients will be candidates for this surgery.
  CHAIRPERSON CANADY:  Dr. Nuwer.
  DR. NUWER:  Is it reasonable to say that this technique is useful, would be used for severe or advanced Parkinson's, but not say that it's a technique to be used for mild or initial stages of Parkinson's?
  DR. VITEK:  No, I don't think I would say that.  I think there's no data for us to address the use in early onset and patients who are mild or early in the course of their disease, that's a whole different question that needs to be addressed.
  Would it be effective?  I believe it would be, sure.
  DR. NUWER:  So that's a very different question --
  DR. VITEK:  Very much --
  DR. NUWER:  For which we don't have data at this time.
  DR. VITEK:  Are we warranted to do this in early -- earlier in the course of disease or not, that wasn't the question addressed in this study.  This study addressed the question if patients were no longer getting adequate control with medical therapy, then they become then effectively cared for with deep brain stimulation, can we improve them?  And I think that's been shown to be true.

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  The third question, Activa Parkinson's Control Therapy increases the duration and quality of "on" time and decreases the duration and severity of "off" time.
  Comments?  Questions?
  DR. EDMONDSON:  I think that might be an important area to review.
  DR. COHEN:  I'd like somebody to clarify because I thought I heard some of the presentation, some differences in what was meant by "on" time and "off" time.  I know what it feels like, but I think for some patients, I mean if you're taking Sinemet, you have on time and off time, but it may mean a different thing to be on and off under this kind of treatment.  I'd like somebody to address that.
  MS. PRITCHARD:  Dr. Olanow?
  DR. OLANOW:  Generally, we medically use the term "on" time to reflect the fact that they're responding to levodopa and the Parkinson features are under control.  We use the term "off" to reflect the fact that the medicine isn't working and that they are suffering from Parkinsonism.
  Now when a person is "on", they can have "on" time in which they're just good and able to move or that "on" time can be complicated by involuntary movements which potentially can be as bad or even worse than the Parkinson features themselves.  So in the extreme state you have patients fluctuating between bad "on" and bad "off" but never getting the good time which is the "on" time without dyskinesia.

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  CHAIRPERSON CANADY:  Other comments?  Mr. Cohen?
  DR. COHEN:  Yes.  The question that I asked earlier I don't think was fully elucidated.  I wanted to be clear.  Is there a difference in the "off" state under deep-brain stimulation than there is under levodopa therapy?  I mean there's "off", for example, I have "on" and "off" during the day, but it's not nearly as severe as was shown in the films.  And I think that's a quality of life issue that should be considered here.  That if you can get better and you could be "on" and not be that effective, in functioning in your life, and if you could get a better "on" state that that would be a valuable contribution.
  Is that true?
  MS. PRITCHARD:  We'll let Dr. Montgomery respond to that.
  DR. MONTGOMERY:  Your points are very well taken.  And in fact, as the data was shown here, the degree of the off periods were much reduced, so with the deep-brain stimulation, even those patients that did have some off periods with the brain stimulation.  The magnitude of those off responses was much, much less, so the therapy not only decreased the amount of off time, but when the patients were experiencing off time, it was significantly reduced as evidenced by the UPRS scores and particularly the Activities of Daily Living.

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  DR. COHEN:  I'm concerned about the credentialing of physicians who are allowed to perform this procedure and I don't know what the answer is, but as a patient I would want at least have information from the professional society or from the patient foundation or something that gave me an indication that the physician had received rigorous training to perform this operation.
  CHAIRPERSON CANADY:  Dr. Hallett?
  DR. HALLETT:  I think you're absolutely right, but I think that the problem that you raise is true of all of medicine and that is one of the problems with the way medicine is regulated in the United States.  It is true of anything, even doing an EMG study I would say the same thing.  It is certainly true, but I don't know how to fix it without altering a lot of rules about how one actually regulates the whole practice of medicine in the United States.
  CHAIRPERSON CANADY:  Dr. Fessler?
  DR. FESSLER:  I would argue that the mechanism to train and credential is already in place and has been for the last 50 to 75 years.  Neurosurgeons train eight years to do this.  Bottom line is this is one of the easiest things we do.  No disrespect intended.  We all think what we do is the hardest.
  The mechanism to train and credential exists.  It's already there.  We don't need to
re-credential for every single thing we do.
  CHAIRPERSON CANADY:  Dr. Edmondson?
  DR. EDMONDSON:  I think a statement from the FDA in any event would be helpful to really underscore that they should be done by highly trained physicians.  I know the onus of responsibilities in individual hospital and JCUHO regulations and all of that and that there are too many factors to consider here and we don't want to press on dictating how physicians should practice.  But I think it really should be underscored that this should be done by physicians experienced in stereotaxic procedures.
  CHAIRPERSON CANADY:  Can I ask that you work on the labeling amendment for that as I move on to the open public hearing portion of the meeting?
  DR. WITTEN:  Excuse me, I'm sorry to interrupt again.  Can you just -- I just would like to know if there are any comments on the safety question?
  CHAIRPERSON CANADY:  I thought we discussed that.
  DR. WITTEN:  We didn't talk about that.
And also any additional comments on the last question which we kind of have already covered.  This one we haven't.
  If there are any additional comments on the safety question.
  DR. COHEN:  I have another comment.
  CHAIRPERSON CANADY:  Dr. Cohen?
  DR. COHEN:  Does this panel recommend follow-on studies to demonstrate, for example, there is a fairly high percentage of adverse consequences.  Would there be, could there be studies that would be done that --
  CHAIRPERSON CANADY:  That can be one of our recommendations within our final motion, yes.
  DR. COHEN:  Okay.

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  MR. COHEN:  Is this somewhat like the Bible where there's a commentary on it?
  CHAIRPERSON CANADY:  Actually, it's less than the Bible because we are, in fact, only recommending.
  (Laughter.)
  Just for clarification, the panel makes a recommendation to the FDA on which the FDA acts.  So it is possible that what we do could in fact be --
  MR. COHEN:  Is there like an explanation of this wording or it's in the transcript, I suppose.
  And the issue I wanted to raise was -- I can't read your name, Dr --
  CHAIRPERSON CANADY:  Dr. Piantadosi.
  MR. COHEN:  He raised the issue of defining Parkinson's patient which I thought ought to be addressed as well.
  CHAIRPERSON CANADY:  To some extent we have in terms of levodopa responsiveness.  The question, I guess, would be raised in conversation as to whether we wish to exclude specifically --
  DR. HALLETT:  I don't think that we have to worry about that particular problem, given the fact that we have specifically noted it as levodopa responsive disease.  I think that that helps to make clear what the diagnosis is as well.  It really serves two purposes.
  CHAIRPERSON CANADY:  Dr. Piantadosi?
  DR. PIANTADOSI:  I would just add to that you have to look very carefully at the patients who were studied.  The eligibility criteria for this trial are fairly restrictive and I personally would be very uncomfortable with statements that allowed one to extrapolate very far beyond that.  These patients all had advanced Parkinson's disease and in fact were a fairly restricted subset of patients by everyone's own admission.
  CHAIRPERSON CANADY:  Dr. Edmondson, I think would be responsive to additional comments regarding this particular issue.
  DR. HALLETT:  Would you like to add the word "advanced"?
  DR. EDMONDSON:  Well, I think that would be helpful, yes.
  CHAIRPERSON CANADY:  So would we like to say "symptoms of advanced levodopa responsive Parkinsonism"?  Would that be acceptable to you, Dr. Edmondson.
  DR. EDMONDSON:  Yes, it would be.
  CHAIRPERSON CANADY:  Let me read it again.  Bilateral Activa Parkinson's control therapy is safe and effective in controlling the symptoms of advanced levodopa responsive Parkinson's disease that are not adequately controlled with medications and then as written.

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  CHAIRPERSON CANADY:  So we would wish a long-term study of the effectiveness over a period of three years, including cognitive and neuropsychological factors.
  MR. COHEN:  I think we also, excuse me, I think we also have to address the question of what specific types of patients and --
  CHAIRPERSON CANADY:  Actually, Dr. Cohen, I'm afraid that I don't think you have conversation in this part.
  Any other comments or does that cover everyone's concerns?
 

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