Accelerated Approvals and Clinical Evidence for Medications for Children
10 affiliations
- 1Data Science, Evidence-Based and Clinical Research Laboratory, Department of Health, Social, and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea
- 2Central Research Centre of Epigenome Based Platform and Its Application for Drug Development, College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea
- 3Section of Digestive Diseases, Department of Medicine, Yale School of Medicine, New Haven, Connecticut
- 4Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut
- 5Section of General Medicine, Department of Medicine, Yale School of Medicine, New Haven, Connecticut
- 6Collaboration for Regulatory Rigor, Integrity, and Transparency, Yale School of Medicine, New Haven, Connecticut
- 7Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea
- 8Severance Underwood Meta-research Center, Institute of Convergence Science, Yonsei University, Seoul, Republic of Korea
- 9Department of Pharmaceutical Biohealth Industry, Chung-Ang University, Seoul, Republic of Korea
- 10Department of Pharmaceutical Regulatory Sciences, Chung-Ang University, Seoul, Republic of Korea
Abstract
Importance: 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]; P = .004) but maintained enrollment of fewer pediatric patients (median, 11 [IQR, 0-61] vs 13 [0-33]; P = .93). Pediatric-only indications had the longest conversion times and lowest PMR fulfillment rates, accounting for 3 of 4 cases with delayed PMR fulfillment.
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.
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BibTeX
@article{mahbub2026accelerated,
title = {{Accelerated Approvals and Clinical Evidence for Medications for Children}},
author = {Nuzhat Mahbub and Sujata Purja and Chul S. Hyun and Joseph S. Ross and Reshma Ramachandran and Jae Il Shin and Eunyoung Kim},
journal = {JAMA Network Open},
year = {2026},
month = nov,
doi = {10.1001/jamanetworkopen.2026.41933},
url = {https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2856227},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Accelerated Approvals and Clinical Evidence for Medications for Children
AU - Nuzhat Mahbub
AU - Sujata Purja
AU - Chul S. Hyun
AU - Joseph S. Ross
AU - Reshma Ramachandran
AU - Jae Il Shin
AU - Eunyoung Kim
PY - 2026
DA - 2026/11/03
JO - JAMA Network Open
DO - 10.1001/jamanetworkopen.2026.41933
UR - https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2856227
AB - Importance: 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]; P = .004) but maintained enrollment of fewer pediatric patients (median, 11 [IQR, 0-61] vs 13 [0-33]; P = .93). Pediatric-only indications had the longest conversion times and lowest PMR fulfillment rates, accounting for 3 of 4 cases with delayed PMR fulfillment. 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.
SN - 2574-3805
ER -