Accelerated Approvals and Clinical Evidence for Medications for Children
Nuzhat Mahbub, Sujata Purja, Chul S. Hyun, Joseph S. Ross, Reshma Ramachandran, Jae Il Shin, Eunyoung KimImportance
The US Food and Drug Administration (FDA) accelerated approval (AA) pathway allows early access to therapies for serious or life-threatening diseases based on surrogate end points reasonably likely to predict clinical benefit. In pediatrics, where evidence generation is challenging, the use and performance of this pathway remain underexamined.
Objective
To characterize preapproval and postapproval studies of drugs granted pediatric AAs.
Design, Setting, and Participants
This cross-sectional study identified preapproval and postapproval studies for pediatric AAs granted between January 1, 2000, and December 31, 2020. Study characteristics and regulatory outcomes were extracted using publicly available sources, including FDA product labels, approval letters, the postmarketing requirements (PMRs) database, ClinicalTrials.gov, and matched peer-reviewed publications as of August 22, 2026.
Exposures
Granting of pediatric AA.
Main Outcomes and Measures
Study characteristics and regulatory outcomes, including time from AA to traditional approval.
Results
From 2000 to 2020, the FDA granted AA to 26 drugs for 35 pediatric indications (7 pediatric-only, 6 pediatric extension, and 22 combined pediatric-adult). Most approvals were supported by extrapolation, including pharmacokinetic bridging. A total of 47 PMRs were issued, primarily for efficacy verification (28 [59.6%]), 26 (55.3%) of which were fulfilled, contributing to traditional approval for 22 indications (62.9%) after a median of 58.1 (IQR, 44.5-80.1) months. Postapproval studies enrolled more patients than preapproval studies (median, 125 [IQR, 58-304] vs 55 [IQR, 27-119];
Conclusions and Relevance
In this cross-sectional study of pediatric AAs between 2000 and 2020, approval frequently relied on surrogate end points and extrapolation with pharmacokinetic bridging studies, with limited pediatric enrollment. Although confirmatory studies typically verified efficacy within 4 years, pediatric-only indications experienced persistent delays, underscoring ongoing challenges in timely pediatric evidence generation.