Chimeric Antigen Receptor (CAR) T-Cell Therapy and Patient Reported Outcomes

CMS evidence review | evidence_type=MEDCAC Meeting | record_type=medcac_meeting | document_id=76 | meeting_date=2018-08-22

On May 16, 2018, the Centers for Medicare & Medicaid Services (CMS) opened a national coverage determination (NCD) analysis on Chimeric Antigen Receptor (CAR) T-cell therapy for Medicare beneficiaries with advanced cancer. As part of this NCD analysis, the Medicare Evidence Development & Coverage Advisory Committee (MEDCAC) will review the evidence specific to patient reported outcomes (PROs). We are seeking recommendations from the MEDCAC panel regarding how existing PRO assessment tools should be incorporated into future clinical studies, including future clinical studies on CAR T-cell therapy. The MEDCAC will focus on specific PRO assessment tools and important characteristics of a PRO assessment tool. The MEDCAC panel will assess whether scientific evidence supports a specific number of outcome assessments, study design characteristics, study duration, and suitable controls for applying PROs to health outcomes research. This meeting will also explore the challenges regarding the validity, reliability, and generalizability of existing PRO assessments. MEDCAC panels do not make coverage determinations, but CMS benefits from their advice.

Actions Taken: June 14, 2018 CMS posts MEDCAC meeting announcement. Posted questions to panel. July 31, 2018 Posted Instructions for Foreign Visitors and Visiting Screening Procedures August 16, 2018 Posted agenda , roster and speaker list for meeting. Also posted presentations and written comments / background materials . August 23, 2018 Posted scoresheet from meeting. December 12, 2018 Posted minutes and transcript from meeting. Webcast of meeting **(registration is not required to view the webcast)** Foreign Visitors Visitor Screening Procedures Registration Information about visiting CMS Driving directions to CMS Recommended hotels Agenda: Federal Register Notice Agenda Medicare Evidence Development & Coverage Advisory Committee August 22, 2018 7:30 AM – 4:30 PM CMS Auditorium Joseph Ross, MD, MHS , Acting Committee Chair Aloysius Cuyjet, MD, MPH , Committee Vice-Chair Tamara Syrek Jensen, JD , Director, Coverage and Analysis Group Maria Ellis , Executive Secretary - 7:30 – 8:00 AM Registration 8:00 – 8:15 AM Opening Remarks - Maria Ellis/Tamara Syrek Jensen, JD/Joseph Ross, MD, MHS 8:15 - 8:30 AM CMS Presentation – Katherine Szarama, PhD 8:30 – 8:45 AM William Go, MD, PhD, Vice President, Clinical Development, Kite, a Gilead Company 8:45 – 9:00 AM Ilia Ferrusi, PhD , Associate Director, HEOR (CAR-T Therapy), US Oncology, Novartis Pharmaceuticals Corporation 9:00 – 9:30 AM Paul G. Kluetz, MD , Associate Director of Patient Outcomes, Oncology Center of Excellence, U.S. Food and Drug Administration 9:30 – 10:10 AM Claire Snyder, PhD, Professor of Medicine, Oncology, and Health Policy & Management, Johns Hopkins Schools of Medicine and Public Health and Elissa Bantug, MHS , Manager of Communication, Education, and Survivorship, Johns Hopkins Breast Cancer Program, Johns Hopkins University 10:10 – 10:40 AM Ethan Basch, MD, Professor, Health Policy and Management, Director, Cancer Outcomes Research Program, Professor, Hematology and Oncology, School of Medicine, UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill 10:40 – 10:55 AM BREAK 10:55 – 11:45 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. **************************************************************************************************** 11:45 – 12:00 PM Open Public Comments Public Attendees who wish to address the panel will be given that opportunity 12:00 – 1:00 PM LUNCH (on your own) 1:00 – 2:00 PM Questions to Presenters 2:00 – 3:00 PM Initial Open Panel Discussion: Dr. Ross 3:00 – 4:00 PM Formal Remarks and Voting Questions The Chairperson will ask each panel member to state his or her position on the voting questions. 4:00 – 4:20 PM Final Open Panel Discussion: Dr. Ross 4:20 – 4:30 PM Closing Remarks/Adjournment: Mrs. Syrek Jensen and Dr. Ross Associated Nca: Chimeric Antigen Receptor (CAR) T-cell Therapy for Cancers (CAG-00451N) Foreign Visitors: Foreign nationals are not authorized unfettered access to CMS facilities. All foreign nationals visiting any CMS facility are required to have prior approval and are assigned a “Hosting Official” who will be responsible for the visit. The request must be submitted no later than 13 business days prior to the scheduled visit, as processing and approval times can be as much as 10 days. Please contact Ruth McKesson via email at Ruth.McKesson@cms.hhs.gov to submit your request by 5:00 pm EDT on Friday, August 3, 2018. Issue: On May 16, 2018, the Centers for Medicare & Medicaid Services (CMS) opened a national coverage determination (NCD) analysis on Chimeric Antigen Receptor (CAR) T-cell therapy for Medicare beneficiaries with advanced cancer. As part of this NCD analysis, the Medicare Evidence Development & Coverage Advisory Committee (MEDCAC) will review the evidence specific to patient reported outcomes (PROs). We are seeking recommendations from the MEDCAC panel regarding how existing PRO assessment tools should be incorporated into future clinical studies, including future clinical studies on CAR T-cell therapy. The MEDCAC will focus on specific PRO assessment tools and important characteristics of a PRO assessment tool. The MEDCAC panel will assess whether scientific evidence supports a specific number of outcome assessments, study design characteristics, study duration, and suitable controls for applying PROs to health outcomes research. This meeting will also explore the challenges regarding the validity, reliability, and generalizability of existing PRO assessments. MEDCAC panels do not make coverage determinations, but CMS benefits from their advice. Minutes: Download meeting minutes Other Material: Transcript 1 Panel Voting Questions: Download scoresheet . Medicare Evidence Development & Coverage Advisory Committee Chimeric Antigen Receptor (CAR) T-Cell Therapy and Patient Reported Outcomes August 22, 2018 On May 16, 2018, the Centers for Medicare & Medicaid Services (CMS) opened a national coverage determination (NCD) analysis on Chimeric Antigen Receptor (CAR) T-cell therapy for Medicare beneficiaries with advanced cancer. As part of this NCD analysis, the Medicare Evidence Development & Coverage Advisory Committee (MEDCAC) will review the evidence specific to patient reported outcomes (PROs). We are seeking recommendations from the MEDCAC panel regarding how existing PRO assessment tools should be incorporated into future clinical studies, including future clinical studies on CAR T-cell therapy. The MEDCAC will focus on specific PRO assessment tools and important characteristics of a PRO assessment tool. The MEDCAC panel will assess whether scientific evidence supports a specific number of outcome assessments, study design characteristics, study duration, and suitable controls for applying PROs to health outcomes research. This meeting will also explore the challenges regarding the validity, reliability, and generalizability of existing PRO assessments. MEDCAC panels do not make coverage determinations, but CMS benefits from their advice. Voting Questions For each voting question, 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 1. How confident are you that each of the following PRO assessments are valid and generalizable to the Medicare population? Patient-Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE); MD Anderson Symptom Inventory (MDASI); European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC—QLQ-C30 (core questionnaire) University of Washington Quality of Life (UW-QOL); Patient-Reported Outcome Measurement Information System (PROMIS); Electronic Self-Report–Cancer (ESRA-C); Functional Living Index–Cancer (FLIC). 2. Considering all PRO assessments in question 1 with greater than or equal to score 2.5, please vote whether or not those PRO assessments combined have available supporting evidence on each of the following desired characteristics. Characteristics Tools (yes/no) A Breadth of measures in emotional, social, and physical well-being B Quick throughput to apply to clinical study C Transferable to community practice settings D Measures are not sensitive to differences in age E Measures are not sensitive to line of therapy F Measures are not sensitive to comorbidities G Measures are generalizable to study of combinations of therapies H Used in net benefit analysis based on symptom burden and well-being Discussion Questions Are there PRO assessments other than those listed in question 1 that have adequately stated evidence-based criteria and processes? Are there additional desired characteristics other than those listed in question 2? 3. How confident are you that each of the following assessment intervals are appropriate measurement periods for a valid PRO assessment? Variable event-dependent frequency interval (i.e. upon admission and after discharge) Fixed time-dependent frequency interval (i.e. weekly, monthly, or yearly) 4. How confident are you that a PRO assessment over the course of the following study durations identifies a meaningful durable treatment effect with a valid PRO? 6 months 12 months 24 months 5. How confident are you that PRO assessments can provide meaningful results when studied with each of the following control populations? patient him/herself, before and after intervention usual care versus protocol-driven intervention historical control Roster: Acting Committee Chair Joseph Ross, MD, MHS Associate Professor Medicine and Public Health Section of General Internal Medicine Department of Medicine Yale University School of Medicine Committee Vice-Chair Aloysius B. Cuyjet, MD, MPH Medical Director HealthCare Partners, IPA MEDCAC Members Joseph S. Cheng, MD, MS, FACS, FAANS Frank H. Mayfield Professor and Chair Department of Neurosurgery University of Cincinnati College of Medicine Diane Civic, PhD, MPH, MSW Medical Policy Analyst Sr. Office of Medical Policy and Technology Assessment Anthem, Inc. Naftali Z. Frankel, MS Patient and Consumer Advocate Melissa M. Garrido, PhD, BS Research Associate Professor Department of Health Law, Policy & Management Boston University School of Public Health Research Health Science Specialist Partnered Evidence-Based Policy Resource Center (PEPReC) Boston VA Healthcare System Thomas F. Goss, PharmD Senior Vice President Boston Healthcare Associates, Inc. Thomas James III, MD, FACP, FAAP Senior Medical Director, MM&Q Highmark, Inc. Joel Lamon, MD, FACP Medical Oncologist/Hematologist California Cancer Associates for Research and Excellence, Inc. Carla Perissinotto, MD, MPH Associate Professor of Medicine School of Medicine University of California, San Francisco Industry Representative Shamiram Feinglass, MD, MBA Vice President Global Government and Medical Affairs Danaher Corporation Guest Panel Members Stephen Gottschalk, MD Member, St. Jude Faculty Chair, Department of Bone Marrow Transplantation & Cellular Therapy Endowed Chair in Bone Marrow Transplantation & Cellular Therapy St. Jude Children's Research Hospital Doug Olson, MD CEO BUHLMANN Diagnostics Corporation James C. Yang, MD Senior Investigator Surgery Branch National Cancer Institute Center for Cancer Research Invited Guest Speakers Elissa Bantug, MHS Manager Communication, Education, and Survivorship Johns Hopkins Breast Cancer Program Johns Hopkins University Ethan Basch, MD, MSc Professor Health Policy and Management Director Cancer Outcomes Research Program Professor Hematology and Oncology School of Medicine UNC Lineberger Comprehensive Cancer Center University of North Carolina at Chapel Hill Ilia Ferrusi, PhD Associate Director HEOR (CAR-T Therapy) US Oncology Novartis Pharmaceuticals Corporation William Go, MD, PhD Vice President Clinical Development Kite, a Gilead Company Paul Kluetz, MD Associate Director for Clinical Science Office of Hematology and Oncology Products Food and Drug Administration Center for Drug Evaluation and Research Office of Oncology Drug Products Claire Snyder, PhD Professor of Medicine Division of General Internal Medicine Program Director BLOCS: Building Lifestyle, Outcomes, & Care Services Research in Cancer Johns Hopkins School of Medicine CMS Liaison Tamara Syrek Jensen, JD Director Coverage and Analysis Group Executive Secretary Maria Ellis Coverage and Analysis Group Speaker List: Medicare Evidence Development & Coverage Advisory Committee August 22, 2018 SPEAKER LIST *6 MINUTES PER SPEAKER* Kathryn E. Flynn, PhD, Associate Professor of Medicine, Senior Scientific Director for Patient-Reported Outcomes CIBMTR®, Milwaukee Campus, Medical College of Wisconsin – Representing: Center for International Blood and Marrow Transplant Research (CIBMTR) Karen Chung, PharmD, MS, Senior Director, Health Economics and Outcomes Research, Juno Therapeutics, a Celgene Company Surbhi Sidana, MD, Assistant Professor of Medicine and Oncology, Fellow, Advanced Hematology, Mayo Clinic, Rochester, MN Cori Abikoff, MD , Medical Director CAR-T, Novartis Pharmaceuticals Corporation Merav Bar, MD, Assistant Member, Fred Hutchinson Cancer Research Center Heather Jim, PhD, Associate Member, Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, FL Gunjan L. Shah, MD, MS, Hematologic Oncologist, Adult Bone Marrow Transplant Service, Center for Health Policy and Outcomes, Memorial Sloan Kettering Cancer Center – Representing: American Society for Blood and Marrow Transplantation Visitor Screening Procedures: Screening procedures will require visitors to empty pockets, remove belts, hats, outerwear jackets (not suit jackets nor sports coats), and large pieces of jewelry and place in provided bins for x-ray screening. Small and loose items (e.g., purses, laptop computers, cell phones) will be placed in bins and larger items (e.g. computer bags) may be placed directly onto the conveyer. All items being carried into the building will require x-ray screening. After all items are placed on the conveyer, visitors will proceed through the walk-through metal detector. If the detector alarms, a security guard will use a wand to clear the alarm. If that clears the alarm, screening is complete and the visitor may enter the facility. In the event that the wand does not clear the alarm, the security guard will physically check the area of the body where the alarm is located. Anytime there is an alarm over a sensitive area of a person's body, the officer will use the back of his/her hands to clear the area. If footwear alarms, then footwear will need to be removed and placed in a bin for x-ray screening. Disabled visitors using a mobility aid (e.g. wheel chair, motorized scooter) that cannot pass through the walk-through metal detector will bypass the device and undergo screening by the officer using a wand and/or pat down.