Timing of Pediatric Drug Approval and Clinical Evidence Submitted to Regulatory Authorities: International Comparison Among Japan, the United States, and the European Union

Many prescription drugs approved for adult use lack pediatric labeling information, resulting in their off-label use in children. Drug regulatory authorities have developed legal and regulatory frameworks to promote pediatric drug development. However, the current state of pediatric indication approval and quality of efficacy evidence, which forms the basis of regulatory approvals, is unknown. Here, we analyzed novel therapeutics approved in Japan, the United States, and the European Union during 2005–2014 to investigate the timing and frequency of pediatric indication approval, and characterized the design of pediatric studies supporting regulatory approval. We found that the United States and European Union experienced a higher frequency of supplemental indication approval in pediatrics based on better-designed studies than Japan. The speed and efficiency of pediatric drug development will improve by coordinating pediatric studies on an international basis. The results also implied the necessity for a robust system of postmarketing monitoring of pediatric efficacy and safety.