MEDCAC Meeting on Studies of New Devices of Self-Management of Type 1 and Insulin-Dependent Type 2 Diabetes in Older Adults

On May 21, 2024, Centers for Medicare & Medicaid Services (CMS) convened the Medicare Evidence Development and Coverage Advisory Committee (MEDCAC) to provide guidance on validated endpoints and minimally-clinically important differences (MCIDs) for clinical studies for devices for self-management of type 1 and insulin-dependent type 2 diabetes in older adults to help the agency with coverage decisions. Devices under consideration included continuous glucose monitors (CGMs), insulin pumps, and automated insulin delivery (AID) systems.

There were 11 MEDCAC committee members who participated in the day long public meeting and 9 members voted on recommendations at the end of the meeting. Committee members voted on the clinical endpoint domains (surrogate markers, health outcomes, quality of life and device-related safety) on a Likert scale and provided comments on the endpoints within each domain. CMS will publish a guidance document for public comment following the MEDCAC meeting. CMS emphasized that the guidance document is not a coverage determination, rather it will be a reference for clinical investigators developing studies and for CMS staff making coverage decisions in this area.

KEY TAKEAWAYS

MEDCAC committee voted to recommend “surrogate markers” as the most important and proximal domain for clinical endpoint measures for devices for self-management of diabetes. Within the surrogate markers domain, the committee emphasized support for Time in Range (TIR) and Time Below Range (TBR) as important endpoints along with time in hypoglycemia, over hemoglobin A1C. While the committee felt that the other three endpoint domains (health outcomes, quality of life, and device safety) were all very important for older adults, they stated concerns that measures under these domains were more subjective to confounding variables. The committee members recommended 0.3% change in A1C and 5% change in TIR as clinically meaningful, while accepting that MCIDs for endpoints will vary based on the individual and the study cohort characteristics. The majority of the committee accepted three months as a sufficient trial duration, especially for surrogate marker endpoints, with preference for three to six month trial duration. Lastly, committee members emphasized that it is the Food and Drug Administration’s (FDA) role to evaluate safety of these devices, therefore, CMS should not consider safety endpoints in coverage decisions.

MEDCAC COMMITTEE MEMBERS

Committee Chair (non-voting member): Joseph Ross, MD, MHS Professor Medicine and Public Health Section of General Internal Medicine Department of Medicine Yale University School of Medicine	Sanket Dhruva, MD, MHS, FACC Assistant Professor of Medicine UCSF School of Medicine Affiliate Faculty, Philip R. Lee Institute for Health Policy Studies Staff Physician (Cardiology), San Francisco VA Medical Center
Melissa M. Garrido, PhD, BS Research Professor Department of Health Law, Policy & Management Boston University School of Public Health Director Partnered Evidence-Based Policy Resource Center (PEPReC) Boston VA Healthcare System	Fred Kobylarz MD, MPH Associate Professor Geriatric Medicine Department of Family Medicine and Community Health Rutgers, The State University of New Jersey
Brian Isetts, RPh PhD, BS-Pharm Professor with Tenure Department of Pharmaceutical Care & Health Systems University of Minnesota College of Pharmacy	Alexander Fanaroff, MD, MHS Assistant Professor of Medicine Division of Cardiology University of Pennsylvania Perelman Center for Advanced Medicine
Fred Kobylarz MD, MPH Associate Professor Geriatric Medicine Department of Family Medicine and Community Health Rutgers, The State University of New Jersey	Heather Young Professor and Founding Dean Emerita of the Betty Irene Moore School of Nursing at the University of California
Joy H. Lewis, DO, PhD, FACP Professor Internal Medicine and Public Health A.T. Still University School of Osteopathic Medicine	Eric Wall, MD, MPH Clinical Associate Professor of Family Medicine, University of Washington
Naftali Z. Frankel, MS, MBEE Consumer & Patient Advocate Director of Precision Medicine Innovation, CMR Adjunct Professor, Johns Hopkins University	Mark D. Carlson, MD, MA (non-voting member) Chief Medical Officer Sr. Vice President for Clinical Affairs Covanos, Inc.

PUBLIC SPEAKERS AND COMMENTERS

Manufacturers

Dexcom
Tandem Diabetes Care
Medtronic
Abbott (written comments only)
Senseonics (written comments only)

Patient Organizations/Coalitions

Diabetes Technology Access Coalition
Junior Diabetes Research Foundations
Partnership to Fight Chronic Disease
Alliance for Aging Research
Time In Range Coalition with diatribe Foundation (written comments only)

Professional Organizations/Physicians

American Diabetes Association
American Association of Clinical Endocrinology
Medha Munshi (Joslin Geriatric Diabetes Program, Harvard)
Greg Forlenza (University of Colorado)
Janet McGill (Washington University of St. Louis)
Davida Kruger (Henry Ford)
Irl Hirsh (University of Washington) – (written comments only)

Trade Organization

AdvaMed (written comments only)

SUMMARY OF PUBLIC COMMENTS

Stakeholders overwhelmingly recommended surrogate markers domain as the most important domain for clinical endpoint measures for devices for self-management of diabetes, with emphasis on TIR along with A1C. Hypoglycemia was highlighted as the highest concern for older adults, with the importance of psychological and physiological relief CGMs and AID systems provide for older adults at risk of hypoglycemia. Stakeholders also highlighted that many individuals with diabetes aging into Medicare today are likely to be on one of these devices and coverage decisions should allow beneficiaries to continue to use their devices once they age into Medicare. Similarly, future clinical trials will have more and more individuals who are already using a device and therefore, MCIDs depend on the baseline at which an individual enters the study. Furthermore, speakers cautioned the committee from recommending rigid MCID thresholds due to the heterogeneity of the impacted population.

Stakeholders agreed that the long-term health outcomes of glycemic control have long been proven and that long-term, large-scale studies are not necessary to know the positive impact diabetes technology has on the user. Two non-diabetes organizations, Partnership to Fight Chronic Disease and Alliance for Aging Research, argued that CMS must carefully consider health disparities within the diabetes population and the impact a rigid coverage guidance could have in further limiting access to the lowest adopters of technology. There was consensus among speakers and commenters that a trial duration of three months is sufficient for studies on devices for self-management of diabetes.

Written comments and presentation submitted to the Committee are public and available on the CMS website (see Resources section below).

SUMMARY OF COMMITTEE RECOMMENDATIONS AND VOTES

The MEDCAC Committee members entered deliberations following the public presentations based on feedback from the experts then voted to rank the four endpoint domains: surrogate markers, health outcomes, quality of life and device-related safety. The Committee used a Likert scale (1) not at all important to (5) extremely important. The Committee Chair, Joseph Ross, and the industry representative, Mark Carlson, were exempt from voting, bringing the number of voting members to nine.

Surrogate markers: mean score 4.7
- 7 voted 5, 1 voted 4, 1 voted 3
- Measures listed: Number of hypoglycemic episodes (<70 mg/dL)- especially episodes of Level 2 hypoglycemia (<54 mg/dL), percentage of time in level 2 hypoglycemia (<54 mg/dL), impact on A1C (MCID = 0.5% change), percentage of time in acceptable glucose range (70-180 mg/dL), percentage of time in hyperglycemia (>180 mg/dL), percentage of time in hypoglycemia (<70 mg/dL)
- Committee members generally agreed that TIR/TBR along with A1C were the most important and proximal clinical endpoints. Multiple members commented that there is a strong association between many of these markers and health outcomes.
- There was a general desire to recognize the importance of hypoglycemia for the older adult population, but the members did not agree on a specific endpoint measure on hypoglycemia.
- Most panelists agreed that a three-to-six-month study was sufficient.

Health Outcomes: mean score 3.3
- 5 voted 4, 2 voted 3, 2 voted 2
- Measures listed: restoration of hypoglycemia awareness, cognitive function changes, diabetes-related emergency department visits, diabetes-related hospitalizations, complications of diabetes, e.g., kidney disease, major adverse cardiovascular events (MACE)

Quality of Life: mean score 3.2
- 1 voted 5, 3 voted 4, 3 voted 3, 1 voted 2
- Measures listed: Audit of Diabetes-Dependent Quality of Life (ADDQoL) questionnaire, Diabetes Distress Scale, Diabetes Impact Measurement Scales (DIMS), Diabetes Treatment Satisfaction Questionnaire, Hypoglycemia Fear Survey, Problem Areas in Diabetes
- Many of the committee members stated that while quality of life measures are incredibly valuable to physicians and patients in making therapy decisions, they are not relevant in terms of coverage for these devices.

Device-related Safety: mean score 3.6
- 1 voted 5, 6 voted 4, 1 voted 3, 1 voted 1
- Measures listed: Hypoglycemia-related emergency department visits, harms such as tissue damage, device discontinuation rates, patient preferences (comparing the device with conventional self-management) and adherence.
- The Committee members generally supported inclusion of more older adults in studies that are submitted to the FDA for safety and accuracy of a device but questioned the measures listed in the domain as relevant.

Conclusion

Mr. Steve Farmer, CMS Chief Strategy Officer for Coverage, concluded the meeting reiterating the reason for the MEDCAC meeting to advise CMS on clinical endpoints for diabetes devices and stated CMS will develop a proposed guidance document that will be open for public comment. He stated that the guidance document can help manufacturers and researchers with how to structure future clinical trials. He did not provide a timeline for when the proposed guidance document will be published.