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4 VOLUME I
5 (Morning Session - November 15, 1999)
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10 HUMAN TUMOR ASSAY SYSTEMS

12 HEALTH CARE FINANCING ADMINISTRATION

13 Medicare Coverage Advisory Committee

14 Laboratory & Diagnostic Services Panel

20 November 15 and 16, 1999

22 Sheraton Inner Harbor Hotel

23 Baltimore, Maryland

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1 Panelists

2 Chairperson

John H. Ferguson, M.D.

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.

Temporary Voting Member

11 Kathy Helzlsouer, M.D.

12 Consumer Representative

Kathryn A. Snow, M.H.A.

Industry Representative

14 James (Rod) Barnes, M.B.A.

15 Carrier Medical Director

Bryan Loy, M.D., M.B.A.

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

Opening Remarks & Overview

4 Grant Bagley, M.D. 10

5 Chairman's Remarks

John H. Ferguson, M.D. 28

Brian E. Harvey, M.D., Ph.D. 30

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

LUNCH 196

VOLUME II

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

Open Committee Discussion 304

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

Adjournment 487

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1 PANEL PROCEEDINGS

2 (The meeting was called to order at

3 8:00 a.m., Monday, November 15, 1999.)

4 MS. TILLMAN: Good Morning, and

5 welcome. Dr. Ferguson, Dr. Bagley, members and

6 guests, I'm Kate Tillman, Executive Secretary of

7 the Laboratory and Diagnostic Services Panel of

8 the Medicare Coverage Advisory Committee. The

9 committee is here today to provide advice and

10 recommendations to the Agency regarding formal

11 requests pertaining to human tumor assay

12 systems. This is the first meeting of the

13 laboratory panel.

14 We are happy to have such a

15 distinguished panel. Thank you all for coming.

16 Today I would like to welcome Dr. Bryan

17 Loy, carrier medical director, from Administar,

18 who is our guest.

19 We have one member of the panel who has

20 received an appointment to temporary voting

21 status, and that is Dr. Kathy Helzlsouer.

22 We have a couple of pieces of business

23 to take care of here. The appointment to

24 temporary voting status. This is signed by

25 Michael Hash, Deputy Administrator for Health

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1 Care Financing Administration. Pursuant to the

2 authority granted under the Medicare Coverage

3 Advisory Committee charter, dated November 24th,

4 1998, I appoint the following person as voting

5 member of the laboratory and diagnostic services

6 panel for the duration of this panel meeting on

7 November 15th and 16th, 1999: Kathy Helzlsouer,

8 M.D. For the record, this individual is a

9 special government employee and is a voting

10 member of the panel under Medicare Coverage

11 Advisory Committee. We have undergone the

12 customary conflict of interest review and have

13 reviewed the material to be considered in this

14 meeting. Signed, Michael M. Hash, Deputy

15 Administrator.

16 The conflict of interest statement:

17 Conflict of interest for the laboratory and

18 diagnostic services panel meeting, November 15th

19 and 16th, 1999. The following announcement

20 addresses conflict of interest issues associated

21 with this meeting and is made part of the record

22 to preclude even the appearance of impropriety.

23 To determine if any conflict existed, the Agency

24 reviewed the submitted agenda and all financial

25 interests reported by the committee

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1 participants. The conflict of interest statutes

2 prohibit special government employees from

3 participating in matters that could affect their

4 or their employers' financial interests. The

5 Agency has determined that all members and

6 consultants may participate in the matters before

7 the committee today.

8 With respect to all other participants,

9 we ask in the interest of fairness that all

10 persons making statements or presentations

11 disclose any current or previous financial

12 involvement in any firm whose products or

13 services they may wish to comment on.

14 Now I am going to turn the meeting over

15 to our chairman, Dr. John Ferguson, who will

16 introduce the panel.

17 DR. FERGUSON: Good morning, and

18 welcome to everybody here. I would like to have

19 the panel members introduce themselves, starting

20 from over here on my far left.

21 MS. SIMMERS: I'm Neysa Simmers.

22 DR. FERGUSON: Could you also say where

23 you're from and what you're doing in life?

24 MS. SIMMERS: I am Lisa Simmers. I'm

25 from Bridgewater, Virginia. I am currently a

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1 health care administrator, and am here in the

2 interest of the laboratory community, I guess.

3 DR. SUNDWALL: I'm David Sundwall. I'm

4 a physician and I'm president of the American

5 Clinical Laboratory Association, in Washington,

6 D.C.

7 DR. FERGUSON: You have to speak into

8 these microphones like a rock singer, I think.

9 DR. KLEE: I am George Klee. I am from

10 Rochester, Minnesota, and I'm a clinical

11 pathologist.

12 DR. FISCHER: Paul Fischer. I'm a

13 family physician from Augusta, Georgia.

14 DR. BROOKS: John Brooks. I am

15 chairman of pathology and laboratory medicine at

16 Roswell Park Cancer Institute.

17 MR. BARNES: Rod Barnes. I am the

18 industry rep on the panel. I work for AlCon Labs

19 in Fort Worth, Texas.

20 DR. BAGLEY: I'm Grant Bagley. I'm the

21 Federal representative on the panel, and director

22 of coverage in HCFA.

23 DR. FERGUSON: I am John Ferguson. I

24 am a practicing neurologist, and I have just

25 retired from the NIH, where I directed the

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1 consensus development program for the last 11

2 years.

3 DR. MURRAY: I'm Robert Murray, a

4 clinical biochemist in practice in Chicago,

5 Illinois.

6 DR. LOY: I'm Bryan Loy. I am with the

7 Kentucky Medicare carrier. I represent the

8 Medicare system at the state carrier level.

9 MS. SNOW: I am Kate Snow. I am the

10 consumer rep on this panel, and I am the director

11 of senior services for Northern Michigan Regional

12 Health Service, and I am an advanced practice

13 nurse in gerontology.

14 DR. KASS: I am Mary Kass. I am

15 chairman of pathology at Washington Hospital

16 Center, and director of integrated laboratory

17 services for MedStar Health.

18 DR. HAUSNER: I am Richard Hausner. I

19 am a pathologist practicing in Houston, Texas.

20 MS. KRAFT: I am Cheryl Kraft,

21 administrative director of laboratory services,

22 Minneapolis.

23 DR. HELZLSOUER: I'm Kathy Helzlsouer,

24 medical oncologist and professor of epidemiology

25 at Johns Hopkins School of Public Health.

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1 DR. MINTZ: I am Paul Mintz. I direct

2 the clinical laboratories and blood bank at the

3 University of Virginia Health System, where I'm a

4 professor of pathology and medicine.

5 DR. FERGUSON: I would like to now turn

6 this over to Grant Bagley. Grant?

7 DR. BAGLEY: I'll just make a couple

8 introductory remarks and sort of bring everyone

9 up to speed about what we're doing and how the

10 process works.

11 The coverage process for Medicare is

12 one which from the very inception of the Medicare

13 program has been marked by local diversity and at

14 the same time, the ability to have national

15 conformity when the science and practice so

16 dictates. It has always been that way and it

17 continues to be that way today.

18 What we're about here is considering

19 issues for national coverage decisions. Very

20 much like the federalism model for everything

21 else, states or in this case Medicare carriers,

22 can have variable policies, but when the science,

23 when the issue is sufficiently justified, we can

24 develop a national coverage policy. That

25 national coverage policy then takes precedence,

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1 and all Medicare carriers in every state and

2 every area follow that same process.

3 So we are going to talk a little bit

4 about how Medicare coverage works and how we are

5 going to deal with it specifically in this issue.

6 What we're talking about is the Medicare

7 statute, and the Medicare statute has one

8 overarching principle, which is in the terms of a

9 bureaucrat, 1862.A.1(a) of the Social Security

10 Act, and this is what it says: That no payment

11 shall be made under Medicare for a service which

12 is not reasonable and necessary for the diagnosis

13 or treatment of an illness or injury. Those are

14 very important words. Reasonable and necessary,

15 diagnosis or treatment, and a disease or

16 illness.

17 Now, reasonable and necessary has never

18 been defined. We've never defined it explicitly

19 and said, this is what it takes to prove

20 reasonable and necessary. But over the years we

21 have articulated principles by which we say,

22 reasonable and necessary means the following

23 things: It doesn't mean safe and effective. It

24 has to be safe and effective to be reasonable and

25 necessary, to be sure, but it has to be a bit

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1 more.

2 So in terms of what we have required to

3 show something is reasonable and necessary, first

4 of all, if it requires a safe and effective

5 determination, and clearance for marketing by the

6 FDA, we've always considered that to be a first

7 step. And second, if it doesn't require

8 clearance for marketing by the FDA, we still make

9 an inquiry that it must be safe and effective.

10 But demonstrated effectiveness is one in which we

11 have said the benefits have to outweigh the

12 anticipated risks. It has to be FDA approved, if

13 required. And there has to be authoritative

14 evidence that it improves outcomes, because after

15 all, that's really what we're talking about.

16 So really, the difference between a

17 threshold issue of is it safe and effective and

18 can it be marketed is somewhat different, you

19 know, and we have to look at it a little bit

20 more. So it has to be safe, to be sure. Any

21 product, even a diagnostic test, has to be safe.

22 It has to be effective, that's clear. But it

23 also has to have benefit which is outweighed, or

24 at least outweighs the risk involved in even the

25 procedure or even a diagnostic test, because it's

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1 going to guide therapy.

2 But not only do the benefits have to

3 outweigh the risks, but there have to be some

4 kind of outcomes, there has to be some

5 improvement in clinical care. Is it an improved

6 outcome, does it give better treatment, does it

7 give better results, or in terms of the

8 diagnostic tests, does it give information which

9 can guide or improve therapy.

10 And finally, does it have value? Is

11 there any value to this procedure? For

12 diagnostic tests, it's an issue; for anything

13 else it can be an issue of does it improve

14 therapy, do we get not necessarily better

15 survival, but do we get improved quality of

16 life.

17 Well, how do we determine this? And

18 again, we've articulated these over the years and

19 said, you know, we have to look at clinical

20 studies and from these clinical studies, we have

21 to be able to make determinations. And so we

22 have to be able to look to available evidence and

23 say, are there fundamental safety questions?

24 Does a product live up to its claims? Does it

25 provide the clinical utility that we can use in

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1 practice, because after all it has to be,

2 remember the statute, reasonable and necessary.

3 And we look at the outcomes and do the clinical

4 studies to provide evidence that there is an

5 improved value from the service.

6 Of course we can look at it in a number

7 of ways. We can look at outcome measures in

8 terms of simply survival, that certainly is the

9 crudest measure we can use for an outcome. But

10 we can look at process changes, which may be

11 indirect, and we can say, how does it influence

12 the disease process, and can we make inferences

13 about value from that. And we can observe just

14 simply effects in terms of does it change a

15 measured process, does it change a physiologic

16 process. Is blood pressure improved? Do we have

17 a metabolic process change? Is cholesterol

18 lowered? And then can we relate those to an

19 outcome.

20 So even when we look at secondary end

21 points, when we are looking at a physiologic

22 measurement or metabolic change, can we make the

23 direct link to an improved outcome. And I think

24 it's going to be important to keep that in mind

25 as we look at intermediate end points.

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1 And in terms of looking at the science,

2 this has always been what we've used to determine

3 what's reasonable and necessary. You know, if we

4 look at information, we look at collections of

5 data, and we look at studies, is to keep in mind

6 that we have to consider the bias that can be

7 introduced, are patients selected in less than a

8 random fashion so that the outcomes might be, you

9 know, influenced by the way patients are

10 selected. Do we select patients for one group

11 and then do they become evaluated by another

12 method in terms of trials with more than one

13 arm. Do patients disappear after being entered

14 into the study, and if so, for what reason? Is

15 this going to affect it? Do we have some way of

16 having people evaluate the results of the study

17 without knowing what the outcomes should be or

18 are going to be? And is there an adequate way to

19 control for the information?

20 These are all things to keep in mind

21 when we're considering clinical data and clinical

22 study. Are they big enough? Are we measuring

23 something which is large enough that we can make

24 a determination? Whatever we've measure, have we

25 measured enough to say this is truly an effect?

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1 Do we have enough subjects in here? Do we have

2 enough patients to make that determination?

3 And within Medicare, we always consider

4 what we're dealing with. I mean certainly, some

5 diseases have a very high prevalence, they have a

6 large impact on the Medicare population, and in

7 those situations we need to have a great deal of

8 evidence to make a change. On the other hand,

9 some diseases are not highly prevalent, they deal

10 with just a smaller population of people, and in

11 those cases we have to look at the degree of

12 precision in the clinical studies in a somewhat

13 different way.

14 To consider the natural history of

15 diseases and the issues we're talking about

16 today, we have to consider what the uninfluenced

17 outcome would be in terms of what kind of a

18 difference does it make when we start to alter

19 things. And in looking at clinical studies, we

20 have to consider both the issue as presented and

21 we have to look at the source they came from.

22 I think I was on a panel with some

23 folks from Australia where they do a much -- they

24 have a much different process than we do in terms

25 of deciding their coverage in terms of looking at

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1 not only the science, but once they've looked at

2 the science, they then look second, and they say

3 now that we've decided we're going to cover

4 something based on the science, let's decide if

5 it's worth it, let's look at what it costs and

6 make that determination. And in doing that we

7 made an interesting point, which I think is

8 worthwhile to relate here, and that is that if

9 you're going to look at a survey, you know, if

10 you're out to buy a car and you're looking at a

11 survey, and you want to look at the report of all

12 the new options that are available in new cars,

13 that you're probably going to say it makes a

14 difference to me whether this is from an

15 independent consumer agency or whether this is a

16 report produced by the auto manufacturer. And

17 the same thing ought to be true when we look at

18 studies, when we look at clinical information.

19 We need to look at the source and say, not