A Comparison of Regional Decisions for Doses and Administrations of New Drugs: Concordance, Discordance, and Dependencies

Regional differences in approved drug dosages and administration are shaped by complex factors, including clinical data, prior regulatory decisions, and region-specific considerations. This study investigated how such factors are associated with variations in approved doses across the United States Food and Drug Administration (FDA), European Medicines Agency (EMA), and Pharmaceuticals and Medical Devices Agency (PMDA) in the context of recent global regulatory practices. We analyzed 111 new molecular entities approved in the United States and Japan from 2017 to 2023, incorporating EMA data where available. Dose concordance, defined as agreement between regions on the labeled approved dosing regimen for the same indication, was observed in 77% between PMDA and FDA and 84% between EMA and FDA, higher than rates reported in earlier studies. Nevertheless, significant regional differences remain. Qualitative analysis suggested that discordance in approved doses was associated with a small number of high-level factors, including differences in benefit-risk perspectives, approaches to dose determination, population-related considerations. Quantitative analysis indicated associations with trial design and submission timing. In a subset of 11 products in which FDA approval preceded approvals by other agencies and involved FDA-led dose modifications, patterns were observed that were consistent with potential interdependence in regulatory decision making, while sponsor-driven harmonization and shared evidence bases may also underlie these patterns. These findings suggest that early regulatory engagement and international coordination may support efficient dose selection, although attention must be paid to differing benefit-risk assessment considerations across regions.