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

BPCA - 改善儿童标签外药物的使用 (OLMU)

• 批准号: 10706857
• 负责人: RACHEL GREENBERG
• 金额: $ 31.7万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-28 至 2026-09-27
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10706857
• 关键词: 5 year old; Academia; Adolescent; Adverse reactions; Age; Area; Award; Best Pharmaceuticals for Children Act; Biological Markers; Child; Childhood; Clinical Research; Clinical Trials; Communities; Congresses; Data; Data Analyses; Development; Development Plans; Digoxin; Dose; Drug Industry; Drug Kinetics; Drug Prescriptions; Drug usage; Effectiveness; Event; Goals; Growth; Hospitalization; Incentives; Knowledge; Legal patent; Literature; Neonatal; Newborn Infant; Outcome; Outcome Measure; Patients; Pediatric Research; Pediatrics; Pharmaceutical Preparations; Pharmacodynamics; Pharmacogenomics; Pharmacology; Pharmacology Study; Polypharmacy; Population; Premature Infant; Process; Protocols documentation; Research; Review Literature; Risk; Safety; Science; Statutes and Laws; Study models; Therapeutic; United States Food and Drug Administration; United States National Institutes of Health; Validation; Variant; Vulnerable Populations; Work; clinically relevant; comparative; congenital heart disorder; design; drug development; drug metabolism; effectiveness study; epidemiologic data; epidemiology study; evidence base; fetal; high risk; improved; innovation; medical specialties; off-label drug; off-label use; off-patent; pediatric patients; pharmacokinetic model; safety study; standard of care; study population; success; treatment response

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.

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），美国食品药品监督管理局（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）。尽管立法显著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）药理学研究任务订单的第一次迭代启动了弥合药代动力学（PK）相关数据之间差距的范例（即，PK、药效学、药物基因组学、疗效和安全性数据）以及临床相关结局，如终点、生物标志物和流行病学数据。这种桥接对于以个性化方式有效治疗儿科患者的成功至关重要。 儿科人群，尤其是最年幼的人群（早产儿、新生儿和2-5岁 老年人）与患者的年龄、剂量或适应症相关的标签外药物使用风险最高。长期住院和多种药物也是风险。许多药物具有多种 医学专业的适应症。标签外药物使用的定义存在差异， 文学作品然而，处方药物的循证数据有限， 剂量、短期或长期安全性和有效性是使用的常见定义 药物“标签外”。标签外使用可增加不良反应、治疗无效和非预期事件的风险。这项新的倡议“改善标签外药物的使用， 儿童”将建立在PTN先前研究中获得的科学知识的基础上（任务顺序 2)从2018年到2022年进行，包括以下内容： ·儿童药物动力学群体药代动力学研究（POPS）。 ·地高辛在先天性心脏病儿童中的研究 新任务指令的目标是确定儿童标签外使用的剩余差距， 设计临床研究（系统性文献综述、流行病学研究、群体PK 建模研究，以及创新的安全性和有效性研究） 作为BPCA优先级排序过程的一部分。将从不同研究中获得的知识整合在此任务顺序中，将提供全面的数据 分析将导致改善新生儿（包括母体/胎儿）的治疗方法， 儿童和青少年人群。