Quantifying Disease Severity in Health Technology Assessment in Japan: A Retrospective Analysis Using Quality-Adjusted Life-Year Shortfalls.

Background: Since 2019, Japan has implemented health technology assessments (HTAs) for selected drugs and medical devices. In the HTA system, the incremental cost-effectiveness ratio (ICER), calculated using quality-adjusted life-years (QALYs), is employed to guide price adjustments. However, the current system does not incorporate a quantitative assessment of disease severity. Objectives: This study aimed to evaluate whether severity modifiers based on QALY shortfalls correspond to conditions currently granted special consideration, that is, those eligible for a higher ICER reference value (1.5× the standard), and to explore their implications for Japan's HTA system. Methods: We retrospectively analyzed 32 drugs assessed under Japan's HTA up to March 2025. Absolute shortfall (AS) and proportional shortfall (PS) were calculated using age, sex distribution, and comparator quality-adjusted life expectancy estimates from manufacturer assessments and public assessments. Severity categories were defined as ×1.0 (AS ≤ ×12 or PS ≤0.85), ×1.2 (12 < AS < 18 or 0.85 < PS < 0.95), and ×1.7 (AS ≥18 or PS ≥0.95). The concordance between severity classification and policy-based special consideration was then examined. Results: Twenty-five matched target populations were identified. Mean AS and PS values did not differ significantly between manufacturer and public assessments, although manufacturers tended to report higher shortfalls. All cancer and pediatric cases were classified as ×1.2 or ×1.7, whereas 1 designated intractable disease was classified as having low severity (×1.0). Chronic and infectious diseases fell into higher severity categories despite not currently being subject to special consideration. Weighted mean severity values were comparable to those used in the UK's National Institute for Health and Care Excellence benchmarks. Discussion: The findings revealed both alignment and misalignment between Japan's current HTA policy and severity classification. While cancer and pediatric diseases were consistent with the existing system, some serious diseases might have been overlooked, and the designated intractable disease might not align with quantitative severity criteria. Conclusions: QALY shortfalls may serve as a complementary approach to identifying unmet health needs within Japan's HTA system. To ensure methodological robustness and social acceptance, broader validation, standardized estimation methods, and stakeholder consensus are necessary for effective decision-making.