Analysis of Clinical Trials for Pediatric Drug Development in Japan: Study Designs and Patient Enrollment from 2012 to 2021

Abstract

This study analyzed clinical trial information for small- and medium-molecule drugs approved for pediatric indications in Japan between 2012 and 2021, aiming to elucidate the implementation status and characteristics of pediatric clinical trials, and participation of Japanese pediatric patients. We examined publicly available data from the Pharmaceuticals and Medical Devices Agency website for drugs approved for pediatric indications. The study excluded biopharmaceuticals and public knowledge-based applications. The analysis focused on the status of clinical trial implementation, trial design characteristics, and Japanese pediatric participation. Of 97 products analyzed in this study, 89 (91.8%) received approval based on pediatric clinical trial data. Of 274 clinical trials submitted for evaluation, 173 trials (63.1%) were pediatric trials, 119 (43.4%) of which included Japanese pediatric participants. Early-phase clinical trials accounted for 34.1% of foreign clinical trials, but only 13.8% of domestic trials, with no stand-alone phase I trials conducted in Japan. Implementation rates of randomization and blinding were lower in domestic trials (27.5% and 24.8%, respectively) compared to foreign trials (46.3% and 36.6%). Analysis of Japanese pediatric enrollment showed low participation, with a median of 5.5 Japanese patients enrolled in multi-regional clinical trials and 6 in rare disease trials. Age group analysis revealed that while 86 trials enrolled young children aged 1 to<7 years and 108 trials included children aged 7 to<15 years, only 1 trial enrolled neonates (birth to<4 weeks) and 33 trials included infants (4 weeks to<1 year). The present analysis revealed structural and operational challenges in Japanese pediatric drug development, including limited early-phase trials, underuse of rigorous study designs, and insufficient trials involving younger age groups. Contributing factors may include a shortage of specialized personnel and procedural barriers. While extrapolation using foreign and adult data has supported pediatric drug approvals, early discussion of pediatric development plan for integration into the adult development program─in line with recent regulatory guidance─is essential to generate evidence optimized for Japanese pediatric populations.