The development of a systematic approach to harness real-world evidence for the evaluation of medication safety and effectiveness in children

开发一种系统方法来利用现实世界的证据来评估儿童用药的安全性和有效性

• 批准号: 10739628
• 负责人: Timothy John Savage
• 金额: $ 16.82万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10739628
• 关键词: Address; Adult; Advisory Committees; Age; Agreement; Area; Calibration; Categories; Cellulitis; Cephalexin; Child; Childhood; Clinical; Clinical Data; Clinical Trials; Complement; Controlled Study; Data; Data Files; Data Reporting; Data Set; Data Sources; Databases; Development; Diagnostic; Disease; Drug Prescriptions; Effectiveness; Electronic Health Record; Epidemiologic Methods; Evaluation; Event; Exposure to; FDA approved; Foundations; Generations; Goals; Healthcare; Hospitals; Infant; Insulin-Dependent Diabetes Mellitus; Knowledge; Label; Machine Learning; Measures; Medical; Mentors; Mentorship; Methodology; Methods; Modeling; National Institute of Child Health and Human Development; Omeprazole; Outpatients; Patient Care; Patients; Pediatric Research; Pediatrics; Pharmaceutical Economics; Pharmaceutical Preparations; Pharmacoepidemiology; Pharmacology; Population; Process; Protocols documentation; Public Health Schools; Publishing; Quality of Care; Randomized, Controlled Trials; Ranitidine; Reproducibility; Research; Research Design; Research Personnel; Research Priority; Risk; Safety; Series; Source; Therapeutic Uses; Training; Trimethoprim-Sulfamethoxazole; Visit; Warfarin; Woman; Work; age group; clinical care; clinical practice; comparative effectiveness; comparative safety; design; health care service utilization; improved; medication safety; novel; novel therapeutics; off-label use; pediatric patients; prospective; safety assessment; scaffold; success; venous thromboembolism

Approximately 20% of pediatric outpatient visits result in a prescription. Half of these prescriptions are off label, a number that rises to 80% among infants. The safe and effective prescribing of medications is essential to providing the highest quality care, and yet many children are receiving medications that have not been evaluated in their age group or in their disease area by rigorous randomized controlled trials (RCTs). There is a tremendous amount of data collected in the routine clinical care of patients via electronic health records (EHRs), claims data, and patient-reported data. These “real-world data” (RWD) can be harnessed with advanced epidemiologic methods focused on causal inference to generate “real-world evidence” (RWE) of medication safety and effectiveness. RWE studies, if conducted with scientific rigor, have the potential to complement RCTs and address important evidence gaps in the use of medications in children. This project aims to develop a framework for the rigorous conduct of RWE studies of pediatric medication use through the following specific aims: (1) to emulate 10 RCTs of medication effects in children using routinely collected healthcare data, (2) to evaluate alternative approaches to minimize bias when emulating RCTs in pediatric populations, and (3) to conduct 3 pediatric RWE studies on medication effects in clinical areas that lack RCT evidence. We will use RCTs as our gold-standard and use advanced causal inference and pharmacoepidemiology methods to design RWE studies to emulate published RCTs as closely as possible. Ten model RCTs will provide the scaffold for the evaluation of which methods perform best for the emulation of RCTs using RWE, and under which conditions. We will identify and summarize the methods that lead to the most successful emulation of RCTs. We will use best practice approaches to conduct three novel RWE studies. We will use three large healthcare utilization databases, including publicly and commercially insured children, as sources of RWD to conduct the RWE studies. These databases have detailed diagnostic and prescription information, making them well suited to studying medication use in children. The Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital provides the ideal setting for this endeavor. I will work with a team of mentors with expertise in pharmacoepidemiology, causal inference, comparative safety and effectiveness, pharmacology, and pediatric research to successfully complete the proposed project. This project provides the ideal framework to develop expertise in advanced pharmacoepidemiology and causal inference methods and support the overarching goal of my research: to generate high-quality evidence of medication safety and effectiveness in pediatric patients when no RCT data is available. Hands-on training and direct mentorship will be complemented by coursework at the Harvard T.H. Chan School of Public Health. This endeavor will provide the necessary foundation for me to become an independent investigator in pediatric pharmacoepidemiology.

大约 20% 的儿科门诊患者会开出处方，其中一半是标签外处方。 在婴儿中这一比例上升至 80%，安全有效的药物处方对于预防和治疗至关重要。 提供最高质量的护理，但许多儿童正在接受未经批准的药物治疗 通过严格的随机对照试验（RCT）对其年龄组或疾病领域进行评估。 通过电子健康记录在患者的常规临床护理中收集大量数据 (EHR)、索赔数据和患者报告数据可以利用这些“真实世界数据”(RWD)。 先进的流行病学方法侧重于因果推断，以生成“真实世界证据”（RWE） 如果以科学严谨的方式进行 RWE 研究，就有可能实现药物安全性和有效性。 补充随机对照试验并解决儿童药物使用方面的重要证据差距。 该项目旨在开发一个严格进行 RWE 儿科研究的框架 通过以下具体目标进行药物使用：（1）模拟 10 项关于儿童药物效果的随机对照试验 使用常规收集的医疗保健数据，(2) 评估替代方法，以最大限度地减少偏差 模拟儿科人群中的随机对照试验，以及 (3) 开展 3 项儿科 RWE 研究，研究药物对儿童的影响 缺乏随机对照试验证据的临床领域，我们将使用随机对照试验作为我们的黄金标准，并使用先进的因果关系。 设计 RWE 研究的推理和药物流行病学方法，以密切模拟已发表的 RCT 十个模型随机对照试验将提供评估哪种方法最适合的框架。 使用 RWE 进行 RCT 仿真，以及在什么条件下我们将确定并总结这些方法。 我们将使用最佳实践方法来进行三项新颖的随机对照试验模拟。 RWE 研究将使用三个大型医疗保健利用数据库，包括公共数据库和商业数据库。 受保儿童作为 RWD 的来源进行 RWE 研究，这些数据库有详细的诊断。 和处方信息，使它们非常适合研究儿童的药物使用情况。 布莱根妇女医院药物流行病学和药物经济学部 为这项工作提供了理想的环境，我将与具有专业知识的导师团队合作。 药物流行病学、因果推断、比较安全性和有效性、药理学和儿科 研究成功完成拟议项目提供了理想的开发框架。 先进药物流行病学和因果推理方法的专业知识并支持总体目标 我的研究重点：生成儿科患者用药安全性和有效性的高质量证据 当没有 RCT 数据可用时，实践培训和直接指导将由课程作业补充。 哈佛大学陈曾熙公共卫生学院的这项工作将为我提供必要的基础。 成为儿科药物流行病学的独立研究者。