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

BPCA 儿科治疗剂量、安全性和疗效的创新试验设计

• 批准号: 10019016
• 负责人: KANECIA ZIMMERMAN
• 金额: $ 1.57万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-12 至 2024-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10019016
• 关键词: Academia; Adolescent; Adopted; Adult; Area; Basic Science; Best Pharmaceuticals for Children Act; Biological Markers; Child; Childhood; Clinical; Clinical Research; Clinical Trials; Communities; Congresses; Data; Data Analyses; Development; Development Plans; Disease; Dose; Drug Industry; Drug Labeling; Effectiveness; Future; Growth; Incentives; Individual; Knowledge; Lead; Legal patent; Medicine; National Institute of Child Health and Human Development; Nature; Outcome; Outcome Measure; Patients; Pediatric Research; Pediatrics; Pharmaceutical Preparations; Pharmacology; Population; Process; Protocols documentation; Reporting; Research; Safety; Science; Statutes and Laws; Therapeutic; Therapeutic Trials; Therapeutic Uses; Translational Research; United States Food and Drug Administration; United States National Institutes of Health; Validation; Work; base; clinically relevant; comparative; data integration; data registry; drug development; drug metabolism; efficacy trial; epidemiologic data; improved; innovation; novel therapeutic intervention; off-label drug; off-patent; pediatric patients; personalized therapeutic; pragmatic trial; prevent; programs; randomized trial; trial design

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.

背景和导言 在过去的25年里，科学界，包括学术界，美国国立卫生研究院（NIH），食品和药物管理局（FDA）和制药行业一直致力于提高儿童用药的知识。国会已经通过立法，为儿科药物开发计划提供激励。改进药物开发的实施和监督责任主要委托给FDA（专利药物）和NIH（非专利药物）。尽管立法提高了在儿童中进行的临床研究的数量，但在发育药理学、药物代谢和作用的个体发生以及儿科研究中结果测量和终点的验证等领域仍然存在差距。此外，对失败的疗效试验的知识差距仍然存在，以及阻止FDA对儿科药物贴标签的原因。国家儿童健康与人类发展研究所（NICHD）和科学界的其他人得出结论，基础，转化和临床研究与相关结果（如终点，生物标志物和流行病学数据）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《儿童最佳药物法案》（BPCA）临床项目，特别是儿科试验网络（PTN），开始纳入并采用一种新的范式，促进个性化儿科治疗的临床研究，这将使人们更好地了解疾病过程之间的相互关系，以及整个发育范围内的治疗方法。这需要新的治疗方法，因此需要在BPCA PTN下发布本创新试验设计项目。 本任务指令旨在为PTN提供创新试验设计，这些设计对儿科治疗的发展至关重要，可在当前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： ·平台试验 ·随机实用试验 ·治疗相关注册 从临床试验中收集的数据（包括试验设计、结局指标、生物标志物和终点）最终可以被纳入并用于儿科的许多治疗领域。 根据BPCA优先程序确定的科学需求以及NICHD的优先事项，因此，很明显，尽管所有的个体试验（研究）都可以 提供有用的信息，将从本任务顺序中的不同研究中获得的知识整合起来，将提供更全面的数据分析，从而进行更好的科学评估，以确定青少年和儿童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，但为了保持所进行研究的全面性，有必要收到包括在该任务下进行的所有临床试验的综合数据的最终报告。 这些创新试验设计的结果的整合，将在最后的 该报告将提供数据，以推进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。数据的整合还将告知 并为在NICHD内开发个性化治疗中心提供科学平台。 范围 进行创新的试验设计，将临床相关结局（如终点、生物标志物和流行病学数据）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的剂量、有效性和安全性方面的科学进步和知识差距。为了更好地了解儿科药物的个体发育（发育效应），可能需要从该人群的成人患者中收集数据，以改善儿科的知识差距。