TreeScan to Evaluate the Safety of New Drugs in Pediatric Populations

TreeScan 评估新药在儿科人群中的安全性

• 批准号: 10673144
• 负责人: Krista F Huybrechts
• 金额: $ 61.15万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-28 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10673144
• 关键词: Acceleration; Address; Adult; Adverse drug effect; Adverse effects; Adverse event; Characteristics; Child; Childhood; Clinical; Clinical Research; Clinical Treatment; Complement; Complex; Data; Databases; Development; Drug Targeting; Drug usage; Early Diagnosis; Effectiveness; Electronic Health Record; Ethics; Evaluation; Grant; Healthcare; Heterogeneity; Joints; Label; Left; Link; Methodology; Methods; Monitor; Outcome; Pattern; Pediatrics; Performance; Pharmaceutical Preparations; Pharmacoepidemiology; Population; Predisposition; Public Health; Randomized; Research; Research Personnel; Risk; Safety; Scanning; Signal Transduction; Statistical Methods; System; Testing; Time; Trees; Uncertainty; Update; Vertebral column; adverse outcome; age related; cohort; epidemiology study; innovation; medication safety; novel therapeutics; off-label use; pediatric patients; performance tests; prospective; safety assessment; screening; simulation; statistics; tool; treatment effect; treatment strategy

Children are not small adults; yet we heavily rely on information collected in randomized and non-randomized studies in adult populations to inform treatment strategies for pediatric patients. Historically, children have been protected from research for ethical reasons. However, this well- intentioned protection from the risks and burdens of trials has paradoxically left children more susceptible to the potential risks of drugs used in everyday practice, frequently off-label and without high-quality evidence of efficacy, effectiveness, or safety. The importance of pharmacoepidemiologic drug safety monitoring using routinely collected healthcare data has been increasingly recognized by the FDA, EMA, and other regulators, and forms the backbone for a major component of the nation’s drug safety surveillance system. However, to date, the focus of these initiatives has been on drug safety in adult populations; there is currently no systematic surveillance system targeting drug safety in pediatric populations. To address this evidence gap – which puts pediatric patients at increased risk – we propose to develop and test the performance of TreeScan based approaches for the systematic and simultaneous evaluation of multiple potential adverse outcomes in pediatric populations, and to implement these methods for prospective sequential surveillance of new pediatric medications. TreeScan methods use a hierarchical tree comprising thousands of outcomes and account for multiple testing of correlated hypotheses while systematically screening for potential adverse effects. The methodology has never been used to evaluate drug safety in pediatric patients, where there are unique challenges compared to adult populations. Thus, the methods require further development and refinement. We will test the approach based on real-world examples of established drugs with relatively well characterized safety profiles (Aim 1) as well as plasmode simulations that explore a broad range of plausible clinical contexts in pediatrics (Aim 2). The performance tested approach will then be implemented to prospectively monitor the safety of recently approved drugs and new drugs that will be approved during the early years of the grant (Aim 3). Potential signals will be further evaluated in full-scale epidemiological studies. This project will provide a critically needed tool that could lead to early detection of unsuspected adverse effects of drugs in pediatric populations if they exist and provide reassurance if no safety issues with large effects are detected. The proposed studies are expected to have an immediate and important public health impact by providing comprehensive assessments of the safety profiles for new medications in pediatric populations.

孩子不是小大人；然而，我们严重依赖于随机和