Molecular Pathology Testing to Estimate Prognosis in Cancer

CMS evidence review | evidence_type=MEDCAC Meeting | record_type=medcac_meeting | document_id=69 | meeting_date=2015-03-24

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.

Actions Taken: January 23, 2015 CMS posts MEDCAC meeting announcement, including Federal Register notice. January 23, 2015 Posted questions to panel. March 17, 2015 Posted agenda , roster , speakers list , and presentations [4MB, ZIP] for meeting. March 18, 2015 Posted written comments March 19, 2015 Posted Technology Assessment/MEDCAC Question Crosswalk March 25, 2015 Posted scoresheet from meeting. May 4, 2015 Posted minutes and transcript from meeting. Webcast of meeting Registration Information about visiting CMS Driving directions to CMS Recommended hotels Agenda: Federal Register Notice Agenda Medicare Evidence Development & Coverage Advisory Committee March 24, 2015 7:30 AM – 4:30 PM CMS Auditorium I. Craig Henderson, MD, Acting Chair James Rollins, MD, Director, Division of Items and Devices Maria Ellis , Executive Secretary 7:30 – 8:00 AM Registration 8:00 – 8:15 AM Opening Remarks— Maria Ellis/James Rollins, MD/I. Craig Henderson, MD 8:15 - 8:35 AM CMS Presentation & Voting Questions – Cheryl Gilbreath, PharmD, MBA, RPh 8:35 – 9:20 AM TA Presentation: Sreelatha Meleth, PhD , Senior Research Statistician Social Statistical and Environmental Sciences, RTI International-University of North Carolina at Chapel Hill Evidence Based Practice Center (RTI-UNC EPC) 9:20 – 9:40 AM Barbara Conley, MD , Associate Director, Cancer Diagnosis Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute 9:40 – 10:00 AM Jeffrey S. Ross, MD, Cyrus Strong Merrill Professor and Chair, Department of Pathology and Laboratory Medicine, Albany Medical College 10:00 – 10:05 AM BREAK 10:05 – 10:50 AM Scheduled Public Comments (Refer to Speaker List) 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 Open Public Comments Public Attendees who wish to address the panel will be given that opportunity 11:00 – 12:00 PM Questions to Presenters 12:00 – 1:00 PM LUNCH (on your own) 1:00 – 2:00 PM Initial Open Panel Discussion: Dr. Henderson 2:00 – 3:00 PM Formal Remarks and Voting Questions The Chairperson will ask each panel member to state his or her position on the voting questions. 3:00 – 4:00 PM Final Open Panel Discussion: Dr. Henderson 4:00 – 4:30 PM Closing Remarks/Adjournment: Dr. Rollins & Dr. Henderson Issue: 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. Minutes: Download meeting minutes [PDF, 120KB] Other Material: Transcript 1 Technology Assessment/MEDCAC Question Crosswalk Panel Voting Questions: Download scoresheet March 24, 2015 MEDCAC Questions Molecular Pathology Testing to Estimate Prognosis in Cancer 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: Cancer Type Test to Estimate Prognosis Q1a Q1b Q2 Q3 Adenocarcinoma of the colon and rectum BRAF KRAS Microsatellite instability MLH1 promoter methylation Oncotype DX® Colon Breast cancer (invasive duct and lobular cancers) MammaPrint® Oncotype DX® Breast Non-small cell lung cancers ALK EGFR KRAS 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 — 2 — 3 — 4 — 5 Low Intermediate High Confidence Confidence 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 . 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 . 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. 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 Please discuss whether each factor below might change the generalizability of evidence about prognostic molecular pathology tests in Medicare beneficiaries with cancer: Regulatory status of test (e.g., US Food & Drug Administration (FDA) approved/cleared vs. laboratory-developed test)? Type of performing laboratory (i.e., university medical center laboratories, independent commercial laboratories, or community hospital-based laboratories)? Subgroups in the Medicare beneficiary population (e.g., by age)? 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. Roster: Acting Chair I. Craig Henderson, MD Adjunct Professor of Medicine University of California, San Francisco MEDCAC Members 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 Speakers List: Medicare Evidence Development & Coverage Advisory Committee March 24, 2015 SPEAKER LIST *5 MINUTES PER SPEAKER* 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