BPCA - IMPROVING OFF-LABEL MEDICATION USE IN CHILDREN (OLMU)

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)。尽管这些立法大大增加了在儿童中进行的临床研究的数量，但在发育药理学、药物代谢的个体发育以及儿科研究结果衡量标准和终点的验证等领域仍然存在差距。2018年授予儿科试验网络(PTN)的最佳儿童药物法案(BPCA)药理学研究任务令的第一次迭代开始了弥合药代动力学(PK)相关数据(即PK、药效学、药物基因组学、有效性和安全性数据)与临床相关结果(如终点、生物标记物和流行病学数据)之间差距的范式。这种桥梁对于以个性化方式有效治疗儿科患者的成功至关重要。 儿童人口，特别是最小的儿童(早产儿、新生儿和2-5岁 与患者的年龄、剂量或适应症相关的非标签药物使用的风险最高。长时间住院和服用多种药物也是风险。很多药物都有多个 跨医学专科的适应症。非标签药物使用的定义在 文学作品。然而，在循证数据有限的情况下开出药物处方 剂量、短期或长期安全性和有效性是对使用意味着什么的常见定义 药品“标签外”。非标签使用会增加不良反应、治疗反应失败和意外事件的风险。这一新倡议的目的是“改善非处方药的使用 儿童“将建立在PTN以前研究中获得的科学知识的基础上(任务顺序 2)2018-2022年进行，包括以下内容： ·儿童机会主义人群药代动力学研究(POPS)。 ·地高辛在先天性心脏病儿童中的研究 新任务顺序的目标将是确定儿童和儿童在标签外使用方面的剩余差距 设计临床研究(系统文献综述、流行病学研究、人群PK 建模研究和创新的安全性和有效性研究)对已识别的非标签药物 作为BPCA优先进程的一部分，已经确定了优先事项。将从不同研究中获得的知识按此任务顺序进行整合，将提供全面的数据 分析将导致改善新生儿(包括产妇/胎儿)的治疗方法， 儿童和青少年群体。

For the last 25 years the scientific community, including academia, the National Institutes of Health (NIH), 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 significantly improved the number of clinical studies conducted in children, gaps remain in areas such as developmental pharmacology, the ontogeny of drug metabolism, and the validation of outcome measures and endpoints in pediatric research. The first iteration of the Best Pharmaceuticals for Children Act (BPCA) Pharmacology Studies Task Order awarded in 2018 to the Pediatric Trials Network (PTN) started the paradigm of bridging the gap between pharmacokinetic (PK) related data (i.e., PK, pharmacodynamic, pharmacogenomic, efficiency, and safety data) with clinically relevant outcomes such as endpoints, biomarkers, and epidemiology data. This bridging is vital to the success of effectively treating pediatric patients in a personalized way. Pediatric populations and particularly the youngest (pre-term infants, newborns, and ages 2-5 years old) are at the highest risk for off-label drug use associated with the patient’s age, dosing or indication. Prolonged hospitalization and polypharmacy are also risks. Many drugs have multiple indications across medical specialties. There is a variation in the definition of off-label drug use in the literature. However, the prescribing of medication with limited evidence-based data on the dosing, short or long-term safety, and effectiveness is a common definition of what it means to use drugs ‘off-label’. Off-label use can increase the risks of adverse reactions, failed treatment responses, and unanticipated events. This new initiative of “Improving Off-label Medication Use in Children” will build upon the scientific knowledge gained in the PTN previous studies (Task Order 2) conducted from 2018-2022 that included the following: • Opportunistic Population Pharmacokinetic Study in Children (POPS). • Digoxin study in children with congenital heart disease The goal of the new task order will be to identify the remaining gaps in off-label use in children and to design clinical research (systematic literature reviews, epidemiology studies, population PK modeling studies, and innovative safety and effectiveness studies) on the identified off-label drugs that have been prioritized as a part of the BPCA prioritization process. The integration of the acquired knowledge from the different studies in this task order will provide a comprehensive data analysis that will lead to improving treatment approaches in neonatal (including maternal/fetal), pediatric, and adolescent populations.