Erythopoiesis Stimulating Agents (ESA) in Anemia Related to Kidney Disease

CMS evidence review | evidence_type=MEDCAC Meeting | record_type=medcac_meeting | document_id=52 | meeting_date=2010-03-24

CMS has called this meeting of the panel to review the available evidence on the use of erythropoiesis stimulating agents (ESAs) to manage anemia in patients who have chronic kidney disease (CKD). Medicare currently does not have a national coverage determination for the use of ESAs for anemia in patients who have CKD. ESAs are synthetic analogs of the hormone erythropoietin. Anemia is prevalent in patients with kidney disease and is more common as CKD progressively worsens. Recombinant genetic technologies are used to produce the ESAs that are commonly used to treat anemia in CKD patients. ESAs raise hemoglobin and hematocrit levels in anemic patients who have CKD, including both those on dialysis and those who do not require dialysis. ESAs were introduced in 1989 and initially administered usually only to patients at risk for blood transfusions. During the subsequent 20 years, ESA use increased, resulting in the common practice of administering ESAs to CKD patients who have anemia, but not necessarily only to those who are at risk for transfusion. Currently, over 95% of end stage renal disease (ESRD) patients receive ESAs. It is unclear how many pre-ESRD CKD patients receive ESAs for anemia. In the fall of 2006 through winter 2007, a succession of published reports highlighted the dangers, including increased mortality, associated with the use of ESAs. These were in addition to other danger signals seen since the introductions of ESAs in 1989. These findings, based on the results of clinical trials, were followed by a series of changes including boxed warnings in the FDA approved labeling for ESAs and a “Dear Doctor Letter” regarding concerns about the safety of ESAs.

Actions Taken: February 19, 2010 Posted questions to panel. March 18, 2010 Posted agenda , roster and speaker list for meeting. March 25, 2010 Posted scoresheet [PDF, 94KB] from meeting. April 13, 2010 Posted presentations [ZIP, 2MB] from meeting. August 3, 2010 Poated minutes [PDF, 139KB] and transcript [PDF, 430KB] from meeting. Agenda: Federal Register Notice Agenda Medicare Evidence Development & Coverage Advisory Committee March 24, 2010 7:30 AM - 4:30 PM CMS Auditorium Clifford Goodman, PhD, Chair Saty Satya-Murti, MD, Vice Chair Louis Jacques, MD, Director, Coverage and Analysis Group Maria Ellis , Executive Secretary 7:30 - 8:00 AM Registration 8:00 - 8:15 AM Opening Remarks— Maria Ellis/ Louis Jacques, MD/ Clifford Goodman, PhD 8:15 - 8:40 AM CMS Presentation & Voting Questions - Maria Ciccanti/Elizabeth Koller, MD 8:40 - 9:05 AM Thomas MaCurdy, PhD, Director, Acumen, LLC DEcIDE 9:05 - 9:15 AM Jerry A. Holmberg, PhD , Senior Advisor for Blood Safety, Executive Secretary of the Advisory Committee on Blood Safety and Availability, HHS 9:15 - 10:00 AM Ajay Singh, MBBS, FRCP, MBA, Physician, Renal Chief, Brigham and Women’s Health, Associate Professor of Medicine, Harvard Medical School 10:00 - 10:15 AM BREAK 10:15 - 11:25 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. 11:25 - 11:35 AM Open Public Comments Public Attendees who wish to address the panel will be given that opportunity 11:35 - 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. Goodman 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. Goodman 4:00 - 4:30 PM Closing Remarks/Adjournment: Dr. Jacques & Dr. Goodman Issue: CMS has called this meeting of the panel to review the available evidence on the use of erythropoiesis stimulating agents (ESAs) to manage anemia in patients who have chronic kidney disease (CKD). Medicare currently does not have a national coverage determination for the use of ESAs for anemia in patients who have CKD. ESAs are synthetic analogs of the hormone erythropoietin. Anemia is prevalent in patients with kidney disease and is more common as CKD progressively worsens. Recombinant genetic technologies are used to produce the ESAs that are commonly used to treat anemia in CKD patients. ESAs raise hemoglobin and hematocrit levels in anemic patients who have CKD, including both those on dialysis and those who do not require dialysis. ESAs were introduced in 1989 and initially administered usually only to patients at risk for blood transfusions. During the subsequent 20 years, ESA use increased, resulting in the common practice of administering ESAs to CKD patients who have anemia, but not necessarily only to those who are at risk for transfusion. Currently, over 95% of end stage renal disease (ESRD) patients receive ESAs. It is unclear how many pre-ESRD CKD patients receive ESAs for anemia. In the fall of 2006 through winter 2007, a succession of published reports highlighted the dangers, including increased mortality, associated with the use of ESAs. These were in addition to other danger signals seen since the introductions of ESAs in 1989. These findings, based on the results of clinical trials, were followed by a series of changes including boxed warnings in the FDA approved labeling for ESAs and a “Dear Doctor Letter” regarding concerns about the safety of ESAs. Minutes: Download Meeting Minutes [PDF, 139KB]. Other Material: Transcript 1 Presentations Panel Voting Questions: CKD/ESA MEDCAC March 24, 2010 Questions How confident are you that there is sufficient evidence to determine whether using a medical intervention (e.g., blood transfusion, iron therapy, or ESAs) to maintain or raise the hemoglobin or hematocrit levels of anemic CKD patients affects each of the health outcomes below? Exercise (activity) tolerance Vascular events (stroke, myocardial infarction, congestive heart failure) Patient perceived quality of life Survival 1 — 2 — 3 — 4 — 5 Low Intermediate High Confidence Confidence Confidence For any health outcome listed in Question 1 for which the panel indicates at least intermediate confidence (mean score ≥ 2.5) in the sufficiency of evidence, how confident are you that maintaining or raising hemoglobin or hematocrit levels of anemic CKD patients improves each such health outcome? 1 — 2 — 3 — 4 — 5 Low Intermediate High Confidence Confidence Confidence a. For any health outcome addressed in Question 2 for which the panel indicates at least intermediate confidence (mean score ≥ 2.5), how confident are you that there is sufficient evidence to determine whether the use of ESAs to maintain or raise hemoglobin or hematocrit levels of CKD patients improves each such health outcome? 1 — 2 — 3 — 4 — 5 Low Intermediate High Confidence Confidence Confidence For any health outcome addressed in Question 3.a. for which the panel indicates at least intermediate confidence (mean score ≥ 2.5), how confident are you that the use of ESAs to maintain or raise hemoglobin or hematocrit levels of CKD patients improves each such health outcome? 1 — 2 — 3 — 4 — 5 Low Intermediate High Confidence Confidence Confidence a. How confident are you that there is sufficient evidence to determine whether the use of ESAs to maintain or raise the hemoglobin or hematocrit levels of anemic CKD patients worsens any health outcome listed in Question 1? 1 — 2 — 3 — 4 — 5 Low Intermediate High Confidence Confidence Confidence For any health outcome addressed in Question 4.a. for which the panel indicates at least intermediate confidence (mean score ≥ 2.5), how confident are you that the use of ESAs to maintain or raise hemoglobin or hematocrit levels of CKD patients worsens each such health outcome? 1 — 2 — 3 — 4 — 5 Low Intermediate High Confidence Confidence Confidence Please discuss any impact of the following factors on the conclusions reached above. Whether the CKD patient is undergoing chronic dialysis or is in pre-dialysis status. Whether the CKD patient has pretreatment baseline hemoglobin levels: < 7 g/dL ≥7g/dL to < 9 g/dL ≥9 g/dL to <12g/dL ≥ 12 g/dL Whether an appropriate target hemoglobin or hematocrit has been set for the CKD patient Whether the ESA dosing strategy has been implemented to minimize the rapidity of hemoglobin or hematocrit rise and/or oscillations in their levels Whether the CKD patient has demonstrated a blunted or “non-response” to interventions to raise hemoglobin or hematocrit Whether the CKD patient has been evaluated to determine the etiology (cause) of the anemia Whether the CKD patient demonstrates cardiac, cerebral or other vascular comorbidities Other What clinical trials designs would be most desirable to fill in any identified evidence gaps? Download scoresheet [PDF, 94KB] Roster: Clifford Goodman, PhD Chair Senior Vice President The Lewin Group Saty Satya-Murti, MD, FAAN Vice Chair Health Policy Consultant Phyllis Atkinson, RN, MS, GNP-BC Gertonological Nurse Practitioner Co-Owner, Advanced Geriatric Education & Consulting, LLC Virginia C. Calega, MD, MBA Vice President Medical Management and Policy Highmark, Inc. Marion Danis, MD Chief, Bioethics Consultation Service Head, Section on Ethics & Health Policy NIH Clinical Center Susan A. Levine, DVM, MS, PhD Vice President Technology Assessment/Editor-in Chief Hayes, Inc. Stephen Pauker, MD, MACP, FACC Professor of Medicine Division of Clinical Decision Making Tufts University School of Medicine Leonard M. Pogach, MD, MBA, FACP Director, Center for Healthcare Knowledge Management for Chronic Complex Illness VA New Jersey Healthcare System James E. Puklin, MD Professor of Ophthalmology Department of Ophthalmology Kresge Eye Institute Chair, Human Investigation Committee Wayne State University School Robert L. Steinbrook, MD Adjunct Associate Professor Medicine and Community and Family Medicine Dartmouth Medical School Industry Representative Eleanor M. Perfetto, PhD, MS Senior Director Evidence Based Strategies Pfizer, Inc. Guest Panel Members Rajiv Agarwal, MD, FAHA, FASN Professor of Medicine Indiana University School of Medicine VA Medical Center Daniel W. Coyne, MD Professor of Medicine Washington University School of Medicine Chromalloy American Kidney Center Joseph M. Messana, MD Associate Professor of Internal Medicine Nephrology Division University of Michigan Health System Guest Speakers Ajay Singh, MBBS, FRCP, MBA Physician Renal Division Brigham and Women’s Hospital Associate Professor of Medicine Harvard Medical CMS Liaison Louis Jacques, MD Director Coverage and Analysis Group Executive Secretary Maria A. Ellis Speaker List: SPEAKER LIST *5 MINUTES PER SPEAKER* Marc A. Pfeffer, MD, PhD, Dean Professor of Medicine, Harvard Medical School Celeste C. Lee, MD, Chief of Staff, Office of the President & CEO, Chancellor for Health Affairs, Duke University Medical Center Wolfgang Winkelmayer, MD, ScD, MPH, Associate Professor of Medicine (Acting), Stanford University School of Medicine, Representing: American Society of Nephrology Kerry Willis, PhD, Senior Vice President, Scientific Activities, National Kidney Foundation Scott McKenzie, MD, Senior Director, Health Economics and Outcomes Research, North America Pharmaceuticals, Centocor Ortho Biotech Products, LP (a Johnson & Johnson Company) Alan S. Kliger, MD, Clinical Professor of Medicine, Yale University School of Medicine and Chairman, Department of Medicine Hospital of St. Raphael, New Haven Connecticut Reshma Kewalramani, MD, Nephrology Therapeutic Area Head, Executive Director, Global Development, Amgen, Inc. Kathe LeBeau, weKAN Program Manager, Renal Support Network Douglas M. Silverstein, MD, Representing: American Society of Pediatric Nephrology Denise Eilers, BSN, RN, Davenport, IA J. Michael Lazarus, MD, Senior Executive Vice President, Fresenius Medical Care NA Shad Ireland, Executive Director, Shad Ireland Foundation Robert S. Rosenson, MD, FACP, FACC, FAHA, Chief of Endocrinology, Diabetes and Metabolism, Coordinator, Preventive Services, Department of Medicine and Senior Cardiologist, SUNY Downstate Medical Center and Daniel J. Cho, Vice President, ProMetrics Inc.