Molecular Pathology Testing to Estimate Prognosis in Cancer

On March 24, 2015, CMS will convene a panel of the Medicare Evidence Development and Coverage Advisory Committee (MEDCAC). The MEDCAC panel will consider the evidence about molecular pathology tests that estimate the prognosis of several frequently encountered types of cancer, including:

• Adenocarcinoma of the colon and rectum;
• Invasive breast cancer; and
• Non-small cell lung cancer.

Outcomes of interest to CMS include both beneficial and harmful outcomes experienced by patients from anti-tumor treatment decisions based on results of tests estimating cancer prognosis. Such outcomes may include, among others: mortality/survival; quality of life; and avoiding harms of anti-cancer treatment. Results of a technology assessment of such tests will be presented.

By voting on specific questions, and by their discussions, MEDCAC panel members will advise CMS about the extent to which it may wish to use existing evidence as the basis for any future determinations about coverage for tests that estimate cancer prognosis. MEDCAC panels do not make coverage determinations, but CMS often benefits from their advice.

January 23, 2015

January 23, 2015

March 17, 2015

March 18, 2015

March 19, 2015

March 25, 2015

May 4, 2015

I. Craig Henderson, MD, Acting Chair
James Rollins, MD, Director, Division of Items and Devices
Maria Ellis, Executive Secretary

7:30 – 8:00 AM

8:00 – 8:15 AM  

8:15 - 8:35 AM

8:35 – 9:20 AM

9:20 – 9:40 AM

9:40 – 10:00 AM

10:00 – 10:05 AM

10:05 – 10:50 AM

Public attendees, who have contacted the executive secretary prior to the meeting, will address the panel and present information relevant to the agenda. Speakers are asked to state whether or not they have any financial involvement with manufacturers of any products being discussed or with their competitors and who funded their travel to this meeting.

10:50 – 11:00 AM

11:00 – 12:00 PM

12:00 – 1:00 PM

1:00 – 2:00 PM

2:00 – 3:00 PM

3:00 – 4:00 PM

4:00 – 4:30 PM

Download meeting minutes [PDF, 120KB]

Download scoresheet

On March 24, 2015, the Medicare Evidence Development & Coverage Advisory Committee (MEDCAC) will consider evidence about molecular pathology tests[1] that estimate prognosis for Medicare beneficiaries with several frequently encountered types of cancer:

Outcomes of interest for CMS reflect beneficiaries’ benefits or harms due to anti-cancer treatment decisions based on test results. Outcomes of interest include (among others) mortality, avoidance of harms of inappropriate anti-cancer treatments, and quality of life.

Voting Questions

For each voting question regarding each molecular pathology test in the grid above, please use the following scale identifying your level of confidence - with a score of 1 being low or no confidence, and 5 representing high confidence:

1. 1. For each prognostic test listed above, how confident are you that existing evidence is sufficient to confirm the analytical validity of the molecular pathology test to estimate prognosis for Medicare beneficiaries with that cancer type?

   For each prognostic test, if the average of voting members’ answers for Question 1a is in the ‘Intermediate’ range (i.e., mean score is ≥ 2.5) please vote on Question 1b.

   2. For each prognostic test listed above, how confident are you that existing evidence is sufficient to confirm the clinical validity of the molecular pathology test to estimate prognosis in Medicare beneficiaries with that cancer type?

   [Note: The definitions of analytical and clinical validity, based on the ACCE assessment process, as used by the Center for Disease Control and Prevention (CDC)’s “Evidence of Genomic Applications in Practice and Prevention” (EGAPP) working group, are summarized at http://www.cdc.gov/genomics/gtesting/EGAPP/recommend/method.htm from which the following table is adapted. The terms ‘diagnostic test’ and ‘prognostic test’ are defined in the footnote.[2]]

   Analytic Validity (Technical Performance)	Clinical Validity (Correlation with Prognosis)
   Test’s ability to accurately and reliably measure analyte or genotype of interest. Related concepts: (Instrumental) Sensitivity (Instrumental) Specificity Assay robustness Quality control	Test’s ability to accurately and reliably estimate the prognosis for the condition of interest. Related concepts: (Clinical) Sensitivity (Clinical) Specificity Positive Predictive Value Negative Predictive Value

   For each prognostic test, if the averages of voting members’ answers for Questions 1a and 1b are both in the ‘Intermediate’ range (i.e., mean score is ≥ 2.5) please vote on Question 2.

2. How confident are you that there is sufficient evidence to conclude that using the molecular pathology test to estimate prognosis affects health outcomes (including benefits and harms) for Medicare beneficiaries with cancer whose anti-cancer treatment strategy is guided by the test’s result?

   For each prognostic test for which the average of voting members’ answers for Question 2 is in the ‘Intermediate’ range (i.e., mean score is ≥ 2.5), please vote on Question 3.

3. How confident are you that there is sufficient evidence to conclude that using the molecular pathology test to estimate prognosis has clinical utility (meaning, that it improves health outcomes either due to increased benefits and/or reduced harms) for Medicare beneficiaries with cancer whose anti-cancer treatment strategy is guided by the test’s result?

Discussion Question

4. Please discuss whether each factor below might change the generalizability of evidence about prognostic molecular pathology tests in Medicare beneficiaries with cancer:
   1. Regulatory status of test (e.g., US Food & Drug Administration (FDA) approved/cleared vs. laboratory-developed test)?
   2. Type of performing laboratory (i.e., university medical center laboratories, independent commercial laboratories, or community hospital-based laboratories)?
   3. Subgroups in the Medicare beneficiary population (e.g., by age)?
   4. Genomic variations within cancers (e.g., diversity of cancer genomes)?

[1] Molecular pathology test is a type of genomic test.

[2] A diagnostic test is defined as a medical test performed to aid in the diagnosis or detection of disease in a beneficiary with signs or symptoms of an illness or injury. In contrast, a prognostic test is a test performed for a beneficiary with cancer that measures or assesses one or more biomarkers, including the biological and genetic properties of the cancer cells, which are thought to be associated with future outcomes.

Acting Chair

I. Craig Henderson, MD
Adjunct Professor of Medicine
University of California, San Francisco

Harry Burke, MD, PhD
Associate Professor
Department of Medicine
Uniformed Services
University of the Health Sciences
Clinician Internal Medicine Service

Josef E. Fischer, MD
William V. McDermott Professor
Department of Surgery
Harvard Medical School and
Beth Israel Deaconess Medical Center

Mark D. Grant, MD, PhD
Associate Director
Technology Evaluation Center
Blue Cross Blue Shield Association

Beverly A. Guadagnolo, MD, MPH
Associate Professor
Department of Radiation Oncology
Division of Radiation Oncology
The University of Texas MD Anderson Cancer Center

Mitchell R. Kamrava, MD
Assistant Clinical Professor
Department of Radiation Oncology
Director, Gynecologic Services
University of California, Los Angeles
UCLA Health System
David Geffen School of Medicine

Marcel Salive, MD, MPH
Medical Officer
National Institute on Aging
National Institute of Health

Maren T. Scheuner, MD, MPH
Chief, Medical Genetics
VA Greater Los Angeles Healthcare System

Diana Zuckerman, PhD
President
National Research Center for Women & Families
Cancer Prevention and Treatment Fund

Industry Representative

Lakshman Ramamurthy PhD
Director
Avalere Health, LLC

Guest Panel Members

Barry M. Berger, MD FCAP
Chief Medical Officer
Exact Sciences Corporation

Invited Guest Speakers

Barbara Conley, MD
Associate Director
Cancer Diagnosis Program
Division of Cancer Treatment and Diagnosis
National Cancer Institute
National Institute of Health

Jeffrey S. Ross, MD
Cyrus Strong Merrill Professor and Chair
Department of Pathology and Laboratory Medicine
Albany Medical College

CMS Liaison

James Rollins, MD
Director
Division of Medical and Surgical Services
Coverage and Analysis Group

Executive Secretary

Maria Ellis
Coverage and Analysis Group

• Jan A. Nowak, MD, PhD, FCAP, Medical Director, Molecular Diagnostics & Cytogenetics, NorthShore University HealthSystem



• Sam Caughron, MD, Laboratory Medical Director at Shawnee Mission Medical Center - Representing: Association for Molecular Pathology



• Bas van der Baan, VP Clinical Affairs & Business Development, Agendia



• Robert Bilkovski, MD, MBA, Senior Associate Medical Director of Medical, Regulatory and Clinical Affairs, Abbott Molecular