{ "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.\n\nObjective: To characterize preapproval and postapproval studies of drugs granted pediatric AAs.\n\nDesign, 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.\n\nExposures: Granting of pediatric AA.\n\nMain Outcomes and Measures: Study characteristics and regulatory outcomes, including time from AA to traditional approval.\n\nResults: 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.\n\nConclusions 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.", "abstract_shown": true, "affiliations": [ "Data Science, Evidence-Based and Clinical Research Laboratory, Department of Health, Social, and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea", "Central Research Centre of Epigenome Based Platform and Its Application for Drug Development, College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea", "Section of Digestive Diseases, Department of Medicine, Yale School of Medicine, New Haven, Connecticut", "Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut", "Section of General Medicine, Department of Medicine, Yale School of Medicine, New Haven, Connecticut", "Collaboration for Regulatory Rigor, Integrity, and Transparency, Yale School of Medicine, New Haven, Connecticut", "Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea", "Severance Underwood Meta-research Center, Institute of Convergence Science, Yonsei University, Seoul, Republic of Korea", "Department of Pharmaceutical Biohealth Industry, Chung-Ang University, Seoul, Republic of Korea", "Department of Pharmaceutical Regulatory Sciences, Chung-Ang University, Seoul, Republic of Korea" ], "article_type": "research article", "arxiv": null, "author_total": 7, "authors": [ { "affs": [ 0, 1 ], "name": "Nuzhat Mahbub" }, { "affs": [ 0, 1 ], "name": "Sujata Purja" }, { "affs": [ 2 ], "name": "Chul S. Hyun" }, { "affs": [ 3, 4, 5 ], "name": "Joseph S. Ross" }, { "affs": [ 4, 5 ], "name": "Reshma Ramachandran" }, { "affs": [ 2, 6, 7 ], "name": "Jae Il Shin" }, { "affs": [ 0, 1, 8, 9 ], "name": "Eunyoung Kim" } ], "bibtex": "https://research.draconitic.com/paper/65h0pddwdc1z2.bib", "cited_by": 0, "doi": "10.1001/jamanetworkopen.2026.41933", "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13732505/", "id": "65h0pddwdc1z2", "issns": [ "2574-3805" ], "landing_url": "https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2856227", "language": "en", "licence": "CC-BY-NC-ND-4.0", "licence_label": "CC BY-NC-ND 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Comments" ], [ "heading", "Health Policy" ], [ "heading", "Online Only" ], [ "heading", "Original Investigation" ], [ "heading", "Research" ] ], "openalex": null, "pdf_url": null, "pmcid": "PMC13732505", "pmid": "42975898", "published": "2026-11-03", "publisher": "American Medical Association (AMA)", "ris": "https://research.draconitic.com/paper/65h0pddwdc1z2.ris", "sources": [ { "first_seen": "2026-11-04T00:26:15Z", "native_id": "10.1001/jamanetworkopen.2026.41933", "source": "crossref", "url": "https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2856227" }, { "first_seen": "2026-11-08T12:22:28Z", "native_id": "PMC13732505", "source": "pmc", "url": "https://doi.org/10.1001/jamanetworkopen.2026.41933" } ], "subjects": [ { "field": "medicine", "origin": "issn:2574-3805", "subfield": "general" } ], "title": "Accelerated Approvals and Clinical Evidence for Medications for Children", "title_text": "Accelerated Approvals and Clinical Evidence for Medications for Children", "type": "peer-reviewed", "updated_at": "2026-11-08T12:22:28Z", "url": "https://research.draconitic.com/paper/65h0pddwdc1z2", "venue": "JAMA Network Open", "versions": [] }