Selig Daniel, Aminu Funmi, Cammarata Sue, Chen Ting, Dolak Lauren, Duprez Stephen, Ecker Stephanie, Gault Lisa, George Sandra, Harkins Margaret, Litchmore Clayton, Serenko Michael, Waverczak William, Girgenti Doug
Melinta Therapeutics, LLC, 389 Interpace Pkwy, Suite 450, Parsippany, NJ 07054, USA.
Tunnell, 1235 Westlake Drive, Suite 280, Berwyn, PA 19312, USA.
Antibiotics (Basel). 2025 Jun 6;14(6):583. doi: 10.3390/antibiotics14060583.
We reviewed Post-Marketing Requirements (PMRs) under the Pediatric Research Equity Act (PREA) for antibiotics approved in adults from 2009 to 2024 to better understand factors associated with PMR study completion. : Initial PMRs, including study design and completion timelines were extracted from Food and Drug Administration (FDA) approval letters. Studies were cross-referenced at clinicaltrials.gov, with follow-up from adult approval to study completion or through 31 December 2024. : Eighteen antibiotics were approved in adults from 2009 to 2024, with 53 associated PREA PMRs. A total of nine PMRs were excluded from analysis (six exclusions for projected study completion dates on or after 12/31/2024, one exclusion due to lack of information, and two exclusions because the study type was not categorizable as Phase 1 or Phase 2). Of the 44 remaining PMRs in the analysis set, the median pediatric study follow-up time from adult approval was 5.3 years (range 0.94 to 11.5 years), with a study completion rate of 54.5% (N = 24). Small- and medium-sized companies had a study completion rate of 10% (N = 2/20) over a median of 6.44 years of follow-up, with no pediatric approvals. Large pharmaceutical corporations had a significantly higher study completion rate of 91.6% (N = 22/24; adjusted hazard ratio 20.3 95%CI, 5.02 to 82.4) over a median follow-up time of 4.7 years and achieved pediatric approval with labelling updates for 75% of antibiotics (N = 6/8). : Compared to larger organizations, smaller pharmaceutical companies have experienced difficulty in PREA PMR antibiotic study completion, which may be related to financial difficulties in the challenging market for antibiotics. To improve PMR study completion, smaller companies require continued financial support and innovation in study design. For pediatric antibiotic development, the FDA accepts the extrapolation of efficacy from well-conducted randomized adult trials (i.e., pharmacokinetics (PK) and the safety approach). Therefore, sponsors should consider the use of single-arm, non-comparative PK and safety study designs to reduce the size and scope of trials. Sponsors should also assess whether the evaluation of an antibiotic is necessary in adolescents, or if data in a surrogate population of adults (e.g., low-weight adults) may serve as adequate evidence for adolescent approval.
我们回顾了2009年至2024年期间成人用抗生素在《儿科研究公平法案》（PREA）下的上市后要求（PMR），以更好地了解与PMR研究完成相关的因素。：初始PMR，包括研究设计和完成时间表，从美国食品药品监督管理局（FDA）批准函中提取。研究在clinicaltrials.gov上进行交叉参考，从成人批准到研究完成或截至2024年12月31日进行随访。：2009年至2024年期间有18种成人用抗生素获得批准，有53项相关的PREA PMR。共有9项PMR被排除在分析之外（6项因预计研究完成日期在2024年12月31日或之后而被排除，1项因缺乏信息而被排除，2项因研究类型无法归类为1期或2期而被排除）。在分析集中剩余的44项PMR中，从成人批准起儿科研究的中位随访时间为5.3年（范围0.94至11.5年），研究完成率为54.5%（N = 24）。中小型公司在中位6.44年的随访中研究完成率为10%（N = 2/20），且无儿科批准。大型制药公司在中位4.7年的随访中研究完成率显著更高，为91.6%（N = 22/24；调整后风险比20.3，95%CI，5.02至82.4），并且75%的抗生素（N = 6/8）获得了儿科批准并更新了标签。：与大型组织相比，小型制药公司在PREA PMR抗生素研究完成方面遇到困难，这可能与抗生素竞争激烈的市场中的财务困难有关。为提高PMR研究的完成率，小型公司需要持续的资金支持和研究设计方面的创新。对于儿科抗生素开发，FDA接受从精心设计的成人随机试验（即药代动力学（PK）和安全性方法）中外推疗效。因此，申办者应考虑使用单臂、非对照的PK和安全性研究设计来缩小试验规模和范围。申办者还应评估是否有必要在青少年中对抗生素进行评估，或者成人替代人群（例如低体重成人）的数据是否可作为青少年批准的充分证据。
