Investigation of Differences Between Manufacturers and Public Analyses in Health Technology Assessment in Japan.

Background: Japan has a unique drug pricing system that in principle reimburses all regulatory-approved drugs. To ensure sustainability, a health technology assessment (HTA) system was introduced in 2019 to adjust the prices of highly innovative and high-budget-impact drugs based on post-reimbursement cost-effectiveness evaluations. Objectives: This study aimed to examine the nature and contributing factors of differences between manufacturers' and public (the Center for Outcomes Research and Economic Evaluation for Health [C2H]) cost-effectiveness analyses for 31 products evaluated under the Japanese HTA system by March 2025. Methods: We conducted descriptive analyses comparing manufacturers' and C2H analyses using publicly available reports. Differences in the assessments of additional benefits, incremental cost-effectiveness ratios (ICERs), and reanalysis items were investigated. We explored issues related to orphan drugs and products granted usefulness premiums for attributes not fully captured by quality-adjusted life-years (QALYs), such as improved convenience and prolonged effect. Results: Among 74 analysis populations across 31 products, 48.6% showed inconsistencies between the manufacturers and C2H in the assessment of additional benefits, outcome measures, or analysis methods used to support those assessments. Inconsistencies in outcome measures and methods increased after the revision of the Japanese HTA system and its guidelines in April 2022. ICER differences were often linked to differences in quality-of-life (QOL) parameters and baseline assumptions. Products granted usefulness premiums for attributes not fully captured by QALYs showed greater ICER differences between the manufacturers and C2H than those without. Although manufacturers often rely on indirect treatment comparisons when evaluating orphan drugs due to limited data and the lack of comparators in clinical trials, these methods were less frequently accepted by C2H due to their associated uncertainty. Discussion: The findings highlight differences between the manufacturers' and C2H analyses, including evaluation of QOL, orphan drugs, and attributes not captured by QALYs. Providing clearer guidance, considering other countries' HTA systems, may help improve consistency in assessments. Conclusions: This study identified key differences and contributing factors under the Japanese HTA system. The findings are expected to inform future refinements of the system and its guidelines, thereby promoting more transparent and predictable evaluations.