BPCA INNOVATIVE TRIAL DESIGNS FOR DOSING, SAFETY, AND EFFICACY IN PEDIATRIC THERAPEUTICS

背景和简介 在过去的25年里，科学界，包括学术界、国家卫生研究院(NIH)、食品和药物管理局(FDA)和制药业，一直在努力提高儿童使用药物的知识。国会已经通过立法，为儿科的药物开发计划提供激励。改进药物开发的实施和监督责任已主要委托给FDA(专利上的药物)和NIH(专利外的药物)。尽管这些立法改善了在儿童中进行的临床研究的数量，但在发育药理学、药物代谢和影响的个体发生以及儿科研究的结果衡量标准和终点的验证等领域仍然存在差距。此外，对于失败的疗效试验的知识差距仍然存在，以及是什么阻止了FDA在儿科对药物进行标签。国家儿童健康与人类发展研究所(NICHD)和科学界的其他机构得出结论，基础、转化性和临床研究与相关结果(如终点、生物标记物和流行病学数据)的协调对于以个性化方式有效治疗儿科患者的未来方向至关重要。 因此，NICHD鼓励儿童最佳药品法案(BPCA)临床计划，特别是儿科试验网络(PTN)，开始纳入和采用一种新的范式，促进个性化儿科疗法的临床研究，从而更好地了解疾病过程和整个发育范围内的疗法之间的相互关系。这需要新的治疗方法，因此需要根据BPCA PTN发布这一创新的试验设计项目。 这项任务令要求PTN提供对促进儿科治疗的重要创新试验设计，从而在当前的PTN周期中促进科学知识的进步和儿科药物标签的改进。这些试验设计包括但不限于以下内容： ·平台试验 ·随机化务实试验 ·与治疗有关的登记 从临床试验整理的数据(包括试验设计、结果测量、生物标记物和终点)最终可以被合并并用于儿科的许多治疗领域。 根据BPCA确定的优先顺序进程以及NICHD的优先事项所确定的科学需求，开展了一项新的医学研究。因此，很明显，尽管所有的个人试验(研究)都可以 为了提供有用的信息，综合这一任务顺序中不同研究获得的知识将提供更全面的数据分析，从而进行更好的科学评估，以确定青少年和儿科人群的最佳治疗方法。更具体地说，虽然这些试验中的每一项都很重要，但收到最终报告是必要的，其中包括根据这项任务进行的所有临床试验的综合数据，以保持所进行研究的综合性。 整合这些创新试验设计的结果，这些结果将在决赛中展示 该报告将提供数据，以促进在儿科人群中使用的治疗药物的剂量、有效性和安全性方面的科学和知识差距。数据的集成也将通知 并为在NICHD内开发个性化治疗中心提供科学平台。 作用域 进行创新性试验设计，将终点、生物标志物和流行病学数据等临床相关结果作为每个方案的一部分，以获得对数据的全面和比较分析，以促进儿科人群中使用的治疗药物在剂量、有效性和安全性方面的科学和知识差距。为了更好地了解药物在儿科中的个体发生(发育效应)，可能需要从这一人群中的成年患者那里收集数据，以改善儿科方面的知识差距。

BACKGROUND AND INTRODUCTION For the last 25 years the scientific community, including academia, the National Institutes of Health (NIH), the Food and Drug Administration (FDA) and the pharmaceutical industry have worked to improve the knowledge of medications used in children. Congress has passed legislations to provide incentives for drug development plans in pediatrics. The responsibility for the implementation and oversight for improving drug development has been delegated primarily to the FDA (for on-patent drugs) and to the NIH (for off-patent drugs). Even though the legislations have improved the number of clinical studies conducted in children, gaps remain in areas such as developmental pharmacology, ontogeny of drug metabolism and effects, and the validation of outcome measures and endpoints in pediatric research. In addition, gaps in knowledge for failed efficacy trials remain as well as what prevent FDA labeling of drugs in pediatrics. The National Institute of Child Health and Human Development (NICHD) and others in the scientific community are concluding that the harmonization of basic, translational, and clinical research with relevant outcomes such as endpoints, biomarkers, and epidemiology data are vital to the future direction of effectively treating pediatric patients in a personalized way. For that reason, the NICHD encourage the Best Pharmaceuticals for Children Act (BPCA) Clinical Program, specifically the Pediatric Trials Network (PTN), to begin to incorporate and adopt a new paradigm of promoting clinical research in personalized pediatric therapeutics that will provide a greater understanding of the interrelationship among disease processes, and therapies across the developmental spectrum. This requires novel therapeutic approaches and hence the need for this Innovative Trial Design project to be issued under the BPCA PTN. This Task Order is for the PTN to provide innovative trial designs important for the advancement of pediatric therapeutics that can lead to advances in scientific knowledge and improvements in pediatric drug labeling in this current PTN cycle. These trial designs include but are not limited to the following: • Platform Trials • Randomized Pragmatic Trials • Therapeutic related Registries The data collated from the clinical trials (including trial designs, outcome measures, biomarkers, and endpoints) can ultimately be incorporated and utilized for many therapeutic areas in pediatric medicine based on the scientific needs determined by the BPCA prioritization process as well as the priorities of the NICHD. Therefore, it is evident that although all individual trials (studies) can provide useful information, the integration of this acquired knowledge from the different studies in this task order will provide a more comprehensive data analysis that will lead to a better scientific assessment to determine the best treatment approaches in adolescent and pediatric populations. More specifically, while each of these trials are important, receipt of the final report that includes the integrated data from all clinical trials performed under this task, is necessary to retain the comprehensive nature of the research conducted. The integration of the results of these innovative trial designs, which will be presented in a final report, will provide data to advance the science and knowledge gaps in the dosing, effectiveness and safety of therapeutics used in the pediatric populations. The integration of the data will also inform and provide a scientific platform for the development of a personalized therapeutics hub within the NICHD. SCOPE To perform innovative trial designs, with clinically relevant outcomes such as endpoints, biomarkers, and epidemiology data included as part of every protocol, to obtain comprehensive and comparative analysis of the data for the advance of the science and knowledge gaps in the dosing, effectiveness and safety of therapeutics used in the pediatric populations. In an effort to better understanding the ontogeny (developmental effect) of drugs in pediatrics, that there may be the need for data to be collected from adult patients in this population in order to improve the knowledge gaps in pediatrics.