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

在过去的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）和制药行业在内的科学界一直在努力提高对儿童用药的认识。国会已经通过立法，为儿科药物开发计划提供激励。实施和监督改进药物开发的责任主要委托给了FDA（非专利药物）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、儿科研究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）药理学研究任务令的第一次迭代开始了缩小药代动力学（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（如终点、生物标志物和流行病学数据）之间差距的范式。这种桥接是至关重要的成功有效地治疗儿科患者的个性化方式。

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.