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1
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4 VOLUME III
5 (Morning Session - November 16, 1999)
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10 HUMAN TUMOR ASSAY SYSTEMS
11
12 HEALTH CARE FINANCING ADMINISTRATION
13 Medicare Coverage Advisory Committee
14 Laboratory & Diagnostic Services Panel
15
16
17
18
19
20 November 15 and 16, 1999
21
22 Sheraton Inner Harbor Hotel
23 Baltimore, Maryland
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25
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1 Panelists
2 Chairperson
John H. Ferguson, M.D.
3
Vice-Chairperson
4 Robert L. Murray, M.D.
5 Voting Members
David N. Sundwall, M.D.
6 George G. Klee, M.D., Ph.D.
Paul D. Mintz, M.D.
7 Richard J. Hausner, M.D.
Mary E. Kass, M.D.
8 Cheryl J. Kraft, M.S.
Neysa R. Simmers, M.B.A.
9 John J.S. Brooks, M.D.
Paul M. Fischer, M.D.
10
Temporary Voting Member
11 Kathy Helzlsouer, M.D.
12 Consumer Representative
Kathryn A. Snow, M.H.A.
13
Industry Representative
14 James (Rod) Barnes, M.B.A.
15 Carrier Medical Director
Bryan Loy, M.D., M.B.A.
16
Director of Coverage, HCFA
17 Grant Bagley, M.D.
18 Executive Secretary
Katherine Tillman, R.N., M.S.
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1 TABLE OF CONTENTS
Page
2 Welcome and Conflict of Interest Statement
Katherine Tillman, R.N., M.A. 5
3
Opening Remarks & Overview
4 Grant Bagley, M.D. 10
5 Chairman's Remarks
John H. Ferguson, M.D. 28
6
Brian E. Harvey, M.D., Ph.D. 30
7
Open Public Comments & Scheduled Commentaries
8 Frank J. Kiesner, J.D. 48
Larry Weisenthal, M.D. 57
9 Randy Stein 92
Richard H. Nalick, M.D. 99
10 William R. Grace, M.D. 108
John P. Fruehauf, M.D., Ph.D. 110
11 James Orr, M.D. 127
Robert M. Hoffman, Ph.D. 131
12 Andrew G. Bosanquet, Ph.D. 136
David Alberts, M.D. 142
13 Robert Nagourney, M.D. 147
David Kern, M.D. 159
14 Daniel F. Hayes, M.D. 168
Bryan Loy, M.D. 178
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LUNCH 196
16
VOLUME II
17
Open Public Comments & Scheduled Commentaries
18 Edward Sausville, M.D. 201
Harry Handelsman, D.O. 227
19 Harry Burke, M.D., Ph.D. 234
Mitchell I. Burken, M.D. 262
20
Open Committee Discussion 304
21
Day One Adjournment 330
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1 TABLE OF CONTENTS (Continued)
2 VOLUME III
3 Opening Remarks - Introduction 336
4 Open Committee Discussion 337
5 Motions, Discussions and
Recommendations 425
6
Adjournment 487
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1 PANEL PROCEEDINGS
2 (The meeting was called to order at
3 8:05 a.m., Monday, November 15, 1999.)
4 DR. FERGUSON: Miss Tillman, our right
5 hand, is here, and has some announcements and
6 pronouncements.
7 MS. TILLMAN: Good morning, and welcome
8 again. First of all, I am going to read the
9 conflict of interest statement again. Conflict
10 of interest for the Laboratory and Diagnostic
11 Services Panel meeting November 15th and 16th,
12 1999. The following announcement addresses
13 conflict of interest issues associated with this
14 meeting, and is made part of the record to
15 preclude even the appearance of an impropriety.
16 To determine if any conflict existed, the Agency
17 reviewed the submitted agenda and all financial
18 interests reported by the committee participants.
19 The conflict of interest statute prohibits
20 special government employees from participating
21 in matters that could affect their or their
22 employer's financial interests. The Agency has
23 determined that all members and consultants may
24 participate in the matters before the committee
25 today.
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1 With respect to all other participants,
2 we ask that in the interest of fairness, that all
3 persons making statements or presentations
4 disclose any current or previous financial
5 involvement with any firm whose products or
6 services they may wish to comment on.
7 In addition to that, we request that
8 anyone with a cell phone please turn it off, so
9 it doesn't disrupt the discussion this morning.
10 Also, as the speakers either come to
11 the microphone or the panel members begin to
12 speak, if you could identify yourself for the
13 record, since we have a court reporter here, and
14 it would make it easier for him to identify who's
15 speaking.
16 And also, anyone who would like a
17 transcript of the meeting can contact Mr. Paul
18 Gasparotti, with Salomon Reporting Services, and
19 he can make a transcript available for you.
20 Dr. Ferguson?
21 Opening Remarks - Introduction
22 DR. FERGUSON: Thank you. This
23 morning, we'll be primarily discussing among the
24 panel members, and then voting on the questions,
25 or the questions proposed as points to vote on.
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1 I would like to remind those in the
2 audience that we would like to keep this
3 restricted to the panel's discussion, except on
4 points of reference where we may need some points
5 clarified from members who presented yesterday,
6 until the 11 to 11:30 session, which we can open
7 up to four or five minute remarks by some who
8 presented their work yesterday.
9 Open Committee Discussion
10 DR. FERGUSON: Now I would like to
11 start this morning and kind of go around among
12 the panel members to get their ideas and their
13 comments and critiques and concerns, and
14 questions on what we've heard, and anything they
15 think that is important that we should know
16 about. Maybe I could start over there on the far
17 right.
18 DR. MINTZ: My concern here is trying
19 to hone in on -- these tests are reasonable, and
20 it's reasonable in a setting of a malignancy to
21 do this. The question I think with which I'm
22 wrestling is when are they necessary. And it's
23 hard to hone in on the data that we have seen on
24 specific situations where we find them
25 necessary. I look forward to further comments
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1 this morning on can we identify situations and
2 disease states where we feel collectively that
3 this test is necessary.
4 I am just beginning to read the
5 articles by Dr. Bosanquet here in CLL, but I do
6 find them interesting, and I'm ready to be
7 persuaded, but I would like a little time to look
8 through them. But as we address these questions
9 this morning, I am interested in hearing further
10 from the participants yesterday as to where we
11 can find specific situations where we might deem
12 this a necessary test. And I look forward to my
13 colleagues trying to identify that situation. I
14 at present have not identified such a situation,
15 but I am open to being persuaded.
16 DR. FERGUSON: Very good. Kathy?
17 DR. HELZLSOUER: Yeah. I agree that
18 intuitively these make sense to be used, and I am
19 wrestling with the same things. I think cancer
20 is too large of a disease entity, and it seems
21 that there probably are settings, and maybe CLL
22 is one of them, where these tests are
23 appropriately used. There is the issue of
24 metastatic versus primary settings, or adjuvant
25 setting, or trying to sort out once they've been
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1 previously treated.
2 And I'm not convinced, although we
3 heard a lot about quality of life, and I believe
4 that's a very good clinical indication for this,
5 that if you can avoid unnecessary chemotherapy,
6 that's extremely relevant and important, but I'm
7 not convinced yet, given the specificity of the
8 overall test results, that we have 80 percent,
9 plus the 10 to 20 percent problem with
10 acquisition of tissues appropriate processing,
11 how many will be spared. And my readings of some
12 of the graphs yesterday and some of the articles
13 here, that if you still have 20 percent that,
14 that's the specificity in the combined group,
15 would you feel comfortable eliminating that for
16 an individual, because there is still a chance 20
17 percent of the time they would still be sensitive
18 in vivo, they will still respond. And when you
19 get down to a metastatic setting when people will
20 choose something for even a 1 percent benefit,
21 it's hard for me to see that you will be
22 eliminating a lot of chemotherapy. So that's one
23 thing that I would like more clarification on.
24 I think that the problem is that there
25 isn't much information on the clinical outcome,
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1 although there's a correlation with survivors,
2 it's the problem we always have with reviewing
3 issues, that responders always do better than
4 non-responders, and it's probably a good marker
5 for responders. But I think we have to see how
6 we can clinically use that in either choosing
7 chemotherapy, and I think the compelling argument
8 is the issue of avoiding unnecessary
9 chemotherapy, but I'm not sure I have the
10 evidence to say that would actually be done in
11 practice.
12 DR. FERGUSON: Thank you. Miss Kraft,
13 do you have some?
14 MS. KRAFT: Cheryl Kraft responding.
15 First of all, what was pointed out yesterday was
16 two different percentages of how many people
17 don't respond to any type of chemotherapy or
18 cancer treatment, one being 70 percent and the
19 other being 76.3 percent. So it's clear that we
20 don't know how to manage cancer patients so that
21 they can survive. So the question to ask is,
22 will the tests that are available to us, these
23 human tissue assay systems, help us in prolonging
24 or help the physician in treating the patient?
25 From what I can tell in the studies
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1 that I've read, that the use of these tests and
2 the way the doctors use these tests in treating
3 patients, that there were no negative effects to
4 the patient or consequence to the patients, with
5 the exception of one trial that was outlined in
6 one of the studies. So that being, do these
7 tests then have, test for drug resistance at a
8 sensitivity that is great enough so that the
9 physicians can interpret the benefit to the
10 patient? Well due to the fact that drug
11 resistance is growing and is definitely
12 multifactorial, as one of the articles said, and
13 the heterogeneity in cancer tumors is great, then
14 are we not, and myself, trying to make sense out
15 of all the articles I have read, and in which
16 cancers and which drugs should be treated for
17 which specific cancers, are we not maybe trying
18 to fit a heterogenetic tumor into a box? I think
19 analytical people try to fit everything into a
20 box.
21 And so what I would like to put forth
22 to the panel is that maybe we should step out of
23 the box and we need to look at, since again, all
24 these tumors are heterogenetic, should we look at
25 just continuing to do what has been done, that
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1 being continuing to test all types of these
2 cancer tumors against all the drugs available to
3 us and see, and continue to treat patients
4 accordingly? Now none of the patients in none of
5 the articles were denied treatment of drugs that
6 they were considered to be resistant to, so
7 taking that into consideration, maybe the studies
8 should continue to be done.
9 However, during that time, this panel
10 needs to think of should the patients, even
11 though this may not be definitively designed for
12 a specific tumor and a specific drug, should the
13 patients really be denied a test? And this is a
14 laboratory test we are talking about. Should
15 they be denied a laboratory test that could
16 possibly benefit them?
17 I think, again, this laboratory test is
18 a tool for a physician. The physician should
19 take advantage of all the tools available to him
20 to treat a patient. And since studies show that
21 only 25 to 30 percent, again, of patients do
22 respond to the test and/or the drugs and/or the
23 correlation of the drugs and the chemotherapy
24 that we have available to them, should we not
25 consider, due consideration to looking at the
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1 advantage of these human tissue assay tests and
2 the resistance that has been found to
3 chemotherapy drugs?
4 DR. FERGUSON: Okay. Thank you.
5 Dr. Hausner?
6 DR. HAUSNER: Dr. Richard Hausner. For
7 me, I would like to take the approach to try and
8 put my comments in the context of my own clinical
9 experience, my own day-to-day, I'm a working
10 pathologist, although I am on the active clinical
11 faculty of Baylor College of Medicine and the
12 University of Texas Health Science Center in
13 Houston. I practice in a community hospital, but
14 I have very long reach in terms of my clinical
15 experience. I have a big practice. And I can
16 tell you that in Houston, Texas, where there is
17 quite a bit of health care going on on a daily
18 basis, not once ever in my life, with all of the
19 cancer patients that I've seen, have I once been
20 asked to harvest tissue for this procedure. Not
21 ever. And I can tell you that if any of the
22 patients in my practice had had this testing,
23 that we would have been involved in the
24 harvesting by definition, because the surgeons
25 would have surely asked. So I know that it
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1 hasn't happened.
2 Nevertheless -- and I came in here
3 reading the source material with that bias,
4 because I had that bias from the very beginning.
5 But nevertheless, somewhere around the middle of
6 yesterday afternoon, my thoughts began to
7 crystallize, and they crystallized during the
8 time that, in the afternoon session when the data
9 was put up to a tremendous amount of scrutiny and
10 a very sophisticated critique, and I thought that
11 it held up pretty darned well. And I have come
12 to the conclusion that while over the past 20
13 years of the research that has developed for this
14 technique, it clearly was a research tool and not
15 ready for prime time, that the decision was
16 correct not to allow this into Medicare's realm
17 and therefore, give it the validity to go
18 forward.
19 Because what is someone's exciting
20 front line technique comes very close to someone
21 else's quackery, and at some point it would have
22 been premature to allow this. But I believe now
23 that the third generation technologies clearly
24 take this beyond a research tool and that from
25 this point forward, I would hope that the
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1 clinical studies will be conducted to refine
2 where this could be best used.
3 Another analogy would be that a, that
4 if this technique is not permitted in its current
5 state, then the panel ought to reconvene and
6 consider removing microbiologic sensitivity
7 testing from the armamentarium of physicians, if
8 this is not approved. The truth, I believe, lies
9 somewhere in the middle, therefore, and just like
10 so many other things we do in medicine, that this
11 is a useful tool, imperfect as it is, and the
12 ground rules may have to be carefully defined,
13 but to turn the test away in its entirety, I
14 believe would be inappropriate.
15 And in closing, I would point to the
16 final paragraph of Dr. Weisenthal's paper in
17 which he talked about whether we use the civil or
18 criminal criteria of preponderance of evidence
19 versus beyond a reasonable doubt. Beyond a
20 reasonable doubt, we don't have. Preponderance
21 of evidence, I believe we do. And therefore, my
22 conclusion is, as a rough sketch, is that
23 something ought to be done towards bringing this
24 test into, as another tool for physicians to
25 use.
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1 DR. FERGUSON: Thank you. Dr. Kass.
2 DR. KASS: Thank you. Mary Kass.
3 First of all, I think my first question
4 was about the testing methodology, but I think
5 that there is overwhelming evidence to show that
6 these tests meet all the normal QC, all of the
7 normal standards that all other laboratory tests
8 have to meet. I think that they're valid, I
9 think that they are reproducible, so the third
10 generation of tests for me is no longer a concern
11 in that respect.
12 The question has been raised about
13 necessary versus clinical utility. I don't know
14 how to define a necessary laboratory test; I
15 think that's really in the mind of the user.
16 When I was in training, which wasn't all that
17 long ago, the emergency room of a downtown urban
18 hospital in Washington, D.C. didn't even have a
19 laboratory open from midnight until eight a.m.
20 because there were no laboratory tests that were
21 necessary to make clinical diagnoses. But we've
22 come a long way since then, and I think medicine
23 has grown and realized that there are many things
24 that can help physicians do a better job in
25 taking care of their patients. So the clinical
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1 utility of this test, I think has been
2 demonstrated, to certainly my satisfaction.
3 The fact that the test is difficult to
4 do because you have to acquire fresh tissue, it
5 has to be shipped in a certain way quickly to a
6 laboratory, that doesn't bother me either. That
7 doesn't change its utility. I remember when we
8 first started doing flow cytometry, the transport
9 of specimens to do flow cytometry on was a big
10 challenge to us. Now we do it routinely and we
11 don't lose specimens in the transport process.
12 It is very intriguing to me that this
13 particular methodology may be very helpful in
14 evaluating new drugs, the number of new
15 chemotherapeutic agents that are rapidly being
16 introduced to try to help us have a greater
17 impact to the treatment of cancer. I think that
18 anything that we could use to help define which
19 modalities have a greater possibility of working
20 and which don't, would be very helpful. I think
21 it also allows the earlier consideration of other
22 treatment modalities for patients, rather than
23 going through a whole course of chemotherapy and
24 waiting for the end point of no response.
25 Earlier in the course of that, a clinician may
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1 have an opportunity to switch a chemotherapeutic
2 drug, or remove one which has a very toxic side
3 effect from the treatment regimen.
4 I guess in summation, I think that we
5 haven't done a terrific job in treating most of
6 the solid tumors. I think everyone is very
7 disappointed in the fact that we haven't been
8 able to have greater success than we have. I
9 think that this is another tool, one of many,
10 that could be available to clinicians that might
11 help, certainly in terms of the quality of life,
12 if we could remove drugs from the treatment
13 regimen that were not effective, and perhaps in a
14 better outcome.
15 I think the patient that testified
16 yesterday, that's one case, it's anecdotal.
17 However, I've practiced pathology for 32 years; I
18 have never seen a patient with widely
19 disseminated pancreatic carcinoma that survived.
20 You have to take notice of that. I think that's
21 worth listening to.
22 So, I think that's the summation of my
23 comments.
24 DR. FERGUSON: Thank you. Miss Snow?
25 MS. SNOW: I'm Kate Snow. I'm the
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1 consumer voice for this panel. I listened very
2 intently to all of yesterday's testimony and I
3 agree that Mr. Stein was very compelling, and I
4 too have never seen a pancreatic cancer
5 survivor. However, I did not know how old this
6 gentleman was, or if he had other comorbidities.
7 I believe that if I were a cancer victim, I would
8 want this study available for my use. I would
9 feel it was reasonable and I would also very much
10 feel it was necessary.
11 Listening to the quality of life and
12 the cost of life that could be gained, and to
13 decrease the burdens for individuals was also
14 very compelling. If it takes the guess out of
15 the therapy that's used, I think it's a very good
16 tool to have available to us.
17 I struggle with whether or not this
18 test will be available in a way where those of us
19 in northern rural Michigan will have access to
20 this kind of tool or not, and what that might
21 look like in the future.
22 I do feel there is a possibility for a
23 cost effectiveness. It may need some more
24 research and looking into exactly how cost
25 effective this could be, both for the medical
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1 community as well as the beneficiary.
2 And I think that's all I have to say
3 for now.
4 DR. FERGUSON: Thank you very much.
5 Dr. Loy?
6 DR. LOY: I'm Dr. Bryan Loy, and I
7 listened also very intently yesterday to the
8 presentations being made. I have a couple of
9 comments, first of all regarding the
10 presentations. I noticed a number of cancers
11 were being elaborated on. I am still not clear
12 at what point in the clinical progression of the
13 disease, or how often the testing should take
14 place.
15 However, having said that, this does
16 sound like this is a tool that be could be very
17 useful. But having listened to the presentations
18 yesterday, again, we were focusing on specific
19 cancers, and to try to take that tool and apply
20 it to all cancers at this point in all clinical
21 scenarios, doesn't seem to be quite reasonab