Prospect of Direct Benefit in Pediatric Trials: Practical Challenges and Potential Solutions.
Prospect of Direct Benefit in Pediatric Trials: Practical Challenges and Potential Solutions.
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DOI：
10.1542/peds.2020-049602
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发表时间：
2021-05
期刊：
影响因子：
8
通讯作者：
Snyder D
中科院分区：
文献类型：
--
作者：
Bhatnagar M;Sheehan S;Sharma I;Baer G;Green D;McCune S;Joffe S;Snyder D
为了开发安全有效的儿童用药，有必要对儿童患者进行临床研究。美国食品和药物管理局（FDA）人类受试者保护条例（21 Code of Federal regulations 50, subpart D）要求，除有限的例外情况外，超过规定风险水平的儿童研究必须为个体儿童提供直接受益的前景，足以证明这些风险是合理的。越来越多的人关注在药物和生物制品开发过程中早期启动儿科临床试验的优点，这使得FDA更密切地关注监管术语“直接受益前景”的含义。Duke-Margolis卫生政策中心与FDA合作，召集生物医学伦理、儿科临床研究和儿科产品开发领域的领先专家以及患者代表召开研讨会，讨论FDA在产品开发科学进步的背景下描述直接获益前景的方法。研讨会的主题包括将成人疗效数据外推到儿童，使用非临床疾病模型，使用建模和模拟来支持儿科给药，以及在临床研究中对生物标志物和替代终点的依赖。本次研讨会讨论了研究者、行业发起人、监管机构和机构审查委员会在评估儿科研究时面临的挑战，并概述了几种方法，以最大限度地提高直接收益的前景，最大限度地减少不必要的风险和负担，并促进儿童及时获得安全有效的药物。
Clinical research in pediatric patients is necessary to develop safe and effective medicines for children. US Food and Drug Administration (FDA) human subject protection regulations (21 Code of Federal Regulations 50, subpart D) require that, with limited exceptions, research in children that exceeds a defined level of risk must offer a prospect of direct benefit to the individual child that is sufficient to justify those risks. Growing attention to the merits of initiating pediatric clinical trials earlier in the drug and biological product development process has led the FDA to look more closely at the meaning of the regulatory term prospect of direct benefit. In collaboration with the FDA, the Duke-Margolis Center for Health Policy convened a workshop with leading experts in the fields of biomedical ethics, pediatric clinical research, and pediatric product development, as well as patient representatives, to discuss the FDA’s approach to characterizing prospect of direct benefit in the context of scientific advances in product development. Workshop topics included the extrapolation of adult efficacy data to children, use of nonclinical models of disease, use of modeling and simulation to support pediatric dosing, and reliance on biomarkers and surrogate end points in clinical research. Discussion from the workshop is provided herein to communicate the challenges that investigators, industry sponsors, regulators, and institutional review boards face when evaluating pediatric research and to outline several approaches to maximize prospect of direct benefit, minimize unnecessary risks and burden, and facilitate timely access to safe and effective medicines for children.