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 25 年里，包括学术界、美国国立卫生研究院 (NIH)、食品和药物管理局 (FDA) 以及制药行业在内的科学界一直致力于提高儿童用药的知识。国会已通过立法，为儿科药物开发计划提供激励措施。改进药物开发的实施和监督责任主要委托给 FDA（针对专利药物）和 NIH（针对非专利药物）。尽管立法显着增加了儿童临床研究的数量，但在发育药理学、药物代谢的个体发育以及儿科研究结果测量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创了弥合药代动力学 (PK) 相关数据（即 PK、药效学、药物基因组学、效率和安全性数据）与临床相关结果（例如终点、生物标志物和药物）之间差距的范例。 流行病学数据。这种桥梁对于成功以个性化方式有效治疗儿科患者至关重要。 儿童群体，尤其是最小的儿童（早产儿、新生儿和 2-5 岁） 年龄、剂量或适应症相关的超说明书用药风险最高。长期住院和服用多种药物也是风险。许多药物具有多种 跨医学专业的适应症。超说明书用药的定义存在差异 文学。然而，基于证据的数据有限的药物处方 剂量、短期或长期安全性和有效性是使用含义的常见定义 药品“标签外”。超说明书使用会增加不良反应、治疗反应失败和意外事件的风险。这项“改善标签外药物使用”的新举措 Children”将建立在 PTN 先前研究中获得的科学知识（任务顺序 2) 2018-2022 年进行，包括以下内容： • 儿童机会性群体药代动力学研究(POPS)。 • 先天性心脏病儿童的地高辛研究 新任务令的目标是确定儿童和儿童中标签外使用的剩余差距。 设计临床研究（系统文献综述、流行病学研究、人群 PK 针对已确定的标签外药物进行建模研究以及创新的安全性和有效性研究） 已作为 BPCA 优先级流程的一部分确定优先级。在此任务顺序中整合从不同研究中获得的知识将提供全面的数据 分析将导致改善新生儿（包括孕产妇/胎儿）的治疗方法， 儿童和青少年人群。