Characterization of studies considered and required under Medicare’s coverage with evidence development program

Introduction In 2005, the Centers for Medicare and Medicaid Services introduced the Coverage with Evidence Development program for items and services with limited evidence of benefit and harm for Medicare beneficiaries, aiming to generate evidence to determine whether they meet the statutory “reasonable and necessary” criteria for coverage. Coverage with Evidence Development requires participation in clinical studies approved by the Centers for Medicare and Medicaid Services (i.e. Coverage with Evidence Development-approved studies) as a condition of coverage. We examined the quality of evidence generated by Coverage with Evidence Development-approved studies compared with those that informed Centers for Medicare and Medicaid Services’ initial Coverage with Evidence Development decisions (i.e. National Coverage Determination studies). Methods Using Centers for Medicare and Medicaid Services’ webpage, we identified all items and services covered under Coverage with Evidence Development and their Coverage with Evidence Development-approved studies. Through searching PubMed and Google Scholar, we identified original research articles that reported results for primary endpoints of Coverage with Evidence Development-approved studies. We then reviewed the initial Coverage with Evidence Development decision memos and identified National Coverage Determination studies that were original research.We characterized and compared Coverage with Evidence Development-approved studies and National Coverage Determination studies. Results From 2005 to 2023, 26 items and services were covered under the Coverage with Evidence Development program, associated with 196 National Coverage Determination studies (170 (86.7%) clinical trials and 26 (13.3%) registries) and 116 unique Coverage with Evidence Development-approved studies (86 (74.1%) clinical trials, 23 (19.8%) registries, 4 (3.4%) claims-based studies, and 3 (2.6%) expanded access studies). Among clinical trial studies, National Coverage Determination studies and Coverage with Evidence Development-approved studies did not differ with respect to multi-arm design (59.4% vs 68.6%; p = 0.15). However, among multi-arm clinical trial studies, National Coverage Determination studies were less likely than Coverage with Evidence Development-approved studies to be randomized (52.5% vs 93.2%; p < 0.001). Overall, National Coverage Determination studies less frequently had ≥ 1 primary endpoint focused on a clinical outcome measure (65.8% vs 87.9%; p = 0.006) and less frequently exclusively enrolled Medicare beneficiaries (3.1% vs 25.9%; p < 0.001). In addition, National Coverage Determination studies had smaller population sizes than Coverage with Evidence Development-approved studies (median 100 (interquartile range, 45–414) vs 302 (interquartile range, 93–1000) patients; p = 0.002). Among Coverage with Evidence Development-approved studies, 59 (50.9%) had not yet publicly reported results for the primary endpoint. Discussion Studies required under Medicare’s Coverage with Evidence Development program more often used randomized study designs, had larger patient populations, enrolled US patients, and focused on clinical outcomes as primary endpoints than studies used to inform initial National Coverage Determinations. However, not all Coverage with Evidence Development-approved studies have thus far reported results, which could create uncertainty for patients, physicians, and payers regarding the clinical benefits of covered items and services. Conclusion The Centers for Medicare and Medicaid Services’ Coverage with Evidence Development program has successfully prompted generation of more robustly designed clinical studies to better inform clinical, regulatory, and coverage decisions compared to studies informing initial coverage decisions. Yet, opportunities exist to further strengthen the design and dissemination of studies required under this program.