Positron emission tomography (PET) is a non-invasive imaging procedure used for measuring the concentrations of positron-emitting radioisotopes within the tissue of living subjects. 2-[F18] fluoro-2-deoxy-D-glucose (FDG) is a radiopharmaceutical that is attracted to higher areas of metabolism. On December 15, 2001, CMS published a Decision Memorandum on a request for broad coverage (CAG-00065) of all oncological indications, heart disease, and neurological disorders. The December 15th decision memorandum stated that CMS had insufficient evidence to support coverage for the indication of Alzheimer's disease/dementia at that time but would refer the issue to MCAC.

Minutes of January 10, 2002 Meeting

OPEN SESSION

Baltimore Convention Center
Baltimore, Maryland

Attendees

Frank J. Papatheofanis, M.D.
Chairperson

Barbara J. McNeil, M.D.
Vice-Chairperson

Janet Anderson
Executive Secretary

Voting Members
Carole R. Flamm, M.D.
Jeffrey C. Lerner, Ph.D.
Steven Guyton, M.D.
Kim J. Burcheil, M.D.

Consumer Representative
Sally Hart, J.D.

Guests
Marilyn Albert, Ph.D.
Keith Johnson, M.D.
Peter Neumann, Sc.D.

CMS Representative
Sean R. Tunis, M.D.

Thursday, January 10, 2002, 8:35 a.m.

The Diagnostic Imaging Panel met on January 10, 2002, to discuss the use of PET in the diagnosis and management of Alzheimer's Disease. The meeting began with a reading of the conflict of interest statement, and the call to order.

Lobbying of Panel Members.   Sean Tunis, M.D. mentioned reports that advocates and stakeholders approached several members of various Medicare Coverage Advisory Committee (MCAC) panels concerning topics being addressed by the MCAC. Dr. Tunis stated that since MCAC committee and panel meetings are designed to be public, and non public conversations between members and advocates or stakeholders is therefore discouraged. At the same time, Dr. Tunis noted that panel members are special government employees only during the time panels are meeting and that members are free to engage in discussion with whomever they choose on their own time, and not as a representative of the MCAC. Dr. Tunis stated that beginning with the next MCAC panel, panelists would be asked to reveal, in addition to the current conflict of interest information, whether they had been approached by any advocate or stakeholder concerning the matters to be discussed.

Charge to Panel.   The chairman, Frank Papatheofanis, M.D., presented the charge to the panel, stating that the panel would closely follow the published agenda. In the course of the presentations to follow, Dr. Papatheofanis encouraged panelists to think about the general discussion questions and the voting question presented by the Centers for Medicare & Medicaid Services (CMS) representative.

CMS Presentation of Request.    A CMS representative presented the panel with the history of the request for coverage, the general discussion questions and the voting question as set forth in the panel's information packet.

Summary of AHRQ Presentation to June 19, 2001 MCAC Executive Committee.   Deborah Zarin, M.D. offered the panel a summary of the June 14, 2001 presentation to the MCAC Executive Committee as well as an overview of the technology assessment decision model, and some definitions that the panel should use in evaluating the assessment.

Presentation of Technology Assessment.    David Matchar, M.D. presented a summary of the Technology Assessment (TA), which came to the following conclusions.

For patients who had had the American Academy of Neurology (AAN) recommended clinical evaluation, treatment without further testing is superior to treatment based on clinical evaluation with the addition of a PET scan. Treating all patients without performing a PET scan would result in all AD patients getting treatment and therefore those with a false positive clinical diagnosis getting unnecessary treatment. Adding a PET scan would decrease the unnecessary treatments by about 10 percentage points, but also decrease treatment of the number of patients who actually have the disease by about 10 percentage points, since the sensitivity of PET is 90%. The TA concluded that because treatment is relatively benign, treatment based on the clinical evaluation only is superior since the increase in true negatives with the use of PET is overshadowed by the concomitant decrease in true positives.

For patients with Mild Cognitive Impairment (MCI), if the evidence for treatment efficacy of cholinesterase inhibitors in patients with dementia can be extrapolated to this population, then empiric treatment would also be superior to treating based on PET scan results.

If the evidence for treatment efficacy can be extrapolated to patients who are currently asymptomatic, but have an elevated risk of having AD by virtue of a first degree relative, then empiric treatment would be superior to treating based on PET scan results. The TA acknowledged PET scanning could be of value if a new treatment was developed that was more effective but had an increase in risk associated to treatment.

Dr. Matchar further commented that there may be other benefits to testing that are not engendered by this analysis, namely that testing may conceivably improve patient end of life planning, decision making about reproduction in a young individual who has a first degree relative with AD, or more compliance with a drug treatment regimen, although none of these scenarios are supported by clinical evidence. He concluded the presentation with possible reasons for not testing, including the suggestion that people who are asymptomatic who are labeled as having disease may have significant reduction in their quality of life, possibly leading to depression, in addition to the negative connotation associated with the diagnosis that may interfere with employment and insurability. Dr. Matchar answered questions from the panel following his presentation.

Scheduled Public Comments.    The panel heard from three scheduled speakers, Daniel Silverman, M.D.; Gary Small, M.D.; and Peter Conti, M.D.

Dr. Silverman presented study summaries showing the sensitivity and specificity of PET in diagnosing neurodegenerative disease in general, and AD specifically. He also presented information showing PET's ability to predict long-term progression of symptoms. He then compared a subset of the UCLA results to the results obtained in the technology assessment. Following his presentation, he answered questions from panel members.

Dr. Small spoke to the panel augmenting some of Dr. Silverman's comments from a clinical perspective. Following his presentation, he answered questions from panel members.

Dr. Conti spoke as a representative of the Society of Nuclear Medicine. He expressed the Society's strong support for the addition of Alzheimer's disease as a CMS reimbursable indication for FDG PET scanning.

Open Public Comments.    Gary Small, M.D. made further comments to the panel.

Open Panel Discussion.    The chairperson facilitated the panel discussions by suggesting the panel members offer their individual opinions concerning the three discussion questions posed by CMS. The guest experts on the panel contributed their thoughts during this phase as well. It was also opined that the charge of MCAC panels is only to make evidence based recommendations to the MCAC Executive Committee (EC). The panel asked that a suggestion be forwarded to CMS to enlist the assistance of experts to form an ad hoc committee for further assessment of decision modeling to be used in the future.

The guest experts opined that there are currently no data regarding use of PET as a replacement for rather than as an adjunct to conventional testing. Following the panelists' comments on each discussion question, Dr. Matchar, Dr. Zarin, Dr. Small, Dr. Silverman and Dr. Conti were afforded an opportunity to make final comments to the panel.

Final Panel Recommendations.

A motion was made and seconded to vote on the following question: Is the evidence adequate to demonstrate that PET has clinical benefit in evaluating patients with suspected AD? Following discussion wherein CMS representatives clarified that the question as posed would apply to patients with probable Alzheimer's, and potentially could include symptoms, mild symptoms, but would not include the asymptomatic population, the motion to vote on that question was withdrawn.

A motion was made and seconded to vote on the following question: Is the evidence adequate to demonstrate that PET has clinical benefit in evaluating patients with possible or probable AD as defined by the current AAN guidelines? To this question, the panel voted unanimously in the negative.

Following a request from Dr. Tunis to address MCI, a motion was made and seconded to vote on the following question: Is the evidence adequate to demonstrate that PET has clinical benefit in evaluating patients with mild cognitive disorder (MCI) as defined by the current AAN guidelines? To this question, the Panel voted unanimously in the negative.

Closing Remarks.   Dr. Tunis informed the panelists and public that in all likelihood, the EC will act upon the recommendations of this panel, since the regulatory change to implement BIPA has not yet taken effect.

Adjournment.   The meeting adjourned at 2:20 p.m.

I approve the minutes of this meeting
as recorded in this summary.
______________________________
Frank J. Papatheofanis, MD, PhD, MPH
Chairperson

Positron emission tomography (PET) is a non-invasive imaging procedure used for measuring the concentrations of positron-emitting radioisotopes within the tissue of living subjects. 2-[F18] fluoro-2-deoxy-D-glucose (FDG) is a radiopharmaceutical that is attracted to higher areas of metabolism. On December 15, 2001, CMS published a Decision Memorandum on a request for broad coverage (CAG-00065) of all oncological indications, heart disease, and neurological disorders. The December 15th decision memorandum stated that CMS had insufficient evidence to support coverage for the indication of Alzheimer's disease/dementia at that time but would refer the issue to MCAC.

Agenda for April 16, 2002 Meeting

8:00 AM - 3:30 PM
Baltimore Convention Center- Rooms 321-322

Harold C. Sox, M.D., Chairperson
Robert H. Brook, M.D., Vice Chairperson
Sean R. Tunis, MD, MSc, Director, Coverage and Analysis Group
Janet A. Anderson, Executive Secretary

Minutes of April 16, 2002 Meeting

Baltimore Convention Center
100 W. Pratt Street
Baltimore, Maryland

Attendees

Harold C. Sox, M.D.
Chairperson

Robert H. Brook, M.D.
Vice Chair (voting)

Janet Anderson
Executive Secretary

Voting Members

Leslie P. Francis, J.D.
John H. Ferguson, M.D.
Alan M. Garber, M.D.
Frank J. Papatheofanis, M.D.
Thomas Holohan, M.D.
Barbara J. McNeil, M.D.
Daisy Alford-Smith, Ph.D.
Wade Aubry, M.D.

CMS Liaison
Sean R. Tunis, M.D.,M.Sc.

Industry Representative
Randel E. Richner, M.P.H.

Consumer Representative
Linda Bergthold, Ph.D.

Tuesday, April 16, 2001. The Executive Committee (EC) of the Medicare Coverage Advisory Committee (MCAC) met on April 16, 2002, to act upon the findings of the MCAC Diagnostic Imaging (DI) Panel on FDG-PET imaging for diagnosis and patient management of Alzheimer’s disease (AD); to discuss the use of decision modeling in policy-making; and to discuss proposed changes to questions presented to MCAC panels.

The meeting began with the introduction of the committee, a reading of the conflict of interest statement, and the call to order.

Review of the Recommendations of DI Panel. Before hearing the summary of the January 10, 2002 meeting from the DI Panel chair and co-chair, Dr. Sox informed the committee that the EC’s purpose was not to question the panel’s review of the evidence, but to determine whether the process used by the panel was consistent with MCAC process as set forth in the guidelines for evaluating effectiveness. Frank Papatheofanis, M.D. and Barbara McNeil, M.D. presented the EC a summary of the panel’s recommendations, including what they perceived to be some of the thoughts that went into the reconstruction of the voting question from that which was originally presented to the panel by CMS. The DI panel chair noted that the meeting minutes detail the reasons for the change in wording of the voting question and that these minutes are available to the public.

Scheduled Public and Open Comments. The committee heard comments from five scheduled public speakers, after which three members of the public also addressed the panel. The scheduled public speakers were: Gary Small, M.D.; Dan Silverman, M.D.; Kirk Frey, M.D.; Peter Conti, M.D.; and Marilyn Albert, M.D.

Action of the Executive Committee on the DI Panel Recommendations. During discussion, the chair and co-chair of the DI Panel stated their opinions that in the revised language voted upon by the panel, the phrase possible or probable AD included the four scenarios expressed by Gary Small, M.D. and others concerning suspected AD. Dan Silverman, M.D. asserted that this still leaves out of consideration those who have dementia but don’t have possible or probable AD under current American Academy of Neurology (AAN) guidelines, and explicitly does not include people who have age associated memory impairment and so forth. During an ensuing discussion, Dr. McNeil and Dr. Papatheofanis reiterated that the intent of the committee was to conclude that there was not adequate evidence to show that there was a benefit to having a PET scan in patients with either mild cognitive impairment or probable or possible Alzheimer’s disease. Following the discussion, each member of the Executive Committee voiced their individual feelings about the issue before the committee.

A motion was then made by Tom Holohan, M.D. and seconded by Daisy Alford-Smith, Ph.D. to “accept the recommendations of the Diagnostic Imaging Panel regarding the use of positron emission tomography (PET) for the diagnosis and patient management of Alzheimer’s disease and other dementias.” The motion passed unanimously with no abstentions.

Use of Decision Modeling in Coverage Policy

Hal Sox, M.D. opened the discussion of decision modeling use in policy decisions with an introductory presentation on analytic decision-making. David Matchar, M.D. then presented a more comprehensive summary of ways to use decision modeling in reaching or recommending clinical health policy decisions. Following the two presentations, the Executive Committee held a discussion that generated a consensus that quantitative decision modeling is a tool that the MCAC should have available when needed in reaching their coverage recommendations. The panel also expressed the opinion that the decision to use models should be made on a case-by-case basis. Members also expressed the opinion that modeling could be used early in a device or technology’s development so that the developers would know what types of data will be most important to capture from clinical trials, thereby enhancing the value of the clinical evidence needed for making coverage recommendations. Members also voiced the opinion that decision models should not replace well-designed clinical trials when those trials are feasible. The members warned against an over-reliance on decision modeling which could result in researchers using modeling instead of conducting valuable research trials. Two members of the public commented that it is their hope that MCAC will somehow integrate the use of analytic decision modeling into their evaluation and recommendation process.

Proposed Changes to Discussion and Voting Questions for MCAC Panels. Sean Tunis, M.D. invited the committee to comment concerning changes to the formation of questions for the panels. Following discussion by the committee, Dr. Tunis said that he may reconvene the methods study group to make a recommendation to be voted on by the Executive Committee on these issues.

Remarks of Jeffrey Kang, M.D.. Jeffrey Kang, M.D., Director of the Office of Clinical Standards and Quality, thanked the committee for their work, and informed them that he would be leaving his post at CMS as of May 3^rd.

Adjournment. The meeting adjourned at 3:16 p.m.