Enhancing Medication Safety in Children with Polypharmacy Using Parent-Reported Symptom Assessments

项目摘要/摘要 越来越多的有医疗复杂性的儿童在门诊接受多药治疗。 设置并每天服用多种高风险药物。多药联用可能导致严重的药物不良事件 (ADES)。最脆弱的儿童有复杂的医疗问题，表现出多种症状，并有 使ADE自我报告不可行的损害，严重限制了临床试验和 上市后的药物监测研究，以发现ADE。詹姆斯·范斯坦博士的首要假设是 在药物改变前后重复的父母报告的症状评估(PRSA)将提供 临床相关信息，改进ADE信号检测，提高用药安全性。这位病人- 面向导师的职业发展奖旨在支持詹姆斯·范斯坦，医学博士， 公共卫生硕士，科罗拉多大学儿科学助理教授，成为一名独立的临床医生兼科学家 并实现成为全国儿科综合药房领先者的长期职业目标 药物安全性研究。他的短期职业目标是：(1)研究导致 综合药房和(2)实施预期的PRSA制度，以指导和监测以下方面的药学服务 高危儿童。范斯坦博士将在3个关键领域完成额外的授课和体验培训 他成功的必要条件：(1)药物流行病学和药物警戒；(2)定量纵向 数据分析；以及(3)前瞻性队列研究的设计和实施。科罗拉多大学 安舒茨医学院为开展儿科综合药房提供独特的研究环境 研究，由成人和儿童联合会之间的合作研究伙伴关系支持 健康结果研究和交付科学(ACCODS)，斯卡格斯药学院和 药学和科罗拉多州儿童医院为患有内科疾病的儿童提供特别护理诊所 复杂性。范斯坦博士著名的研究导师团队Allison Kempe博士(健康服务 研究)、Robert Valuck博士(药物流行病学)、Chris Feudtner博士(患有复杂慢性疾病的儿童 和Diane Fairclough博士(生物统计学)，将指导完成拟议的培训和 研究计划。为了实现他的短期职业目标，范斯坦博士提出了三个研究项目，它们将 促进实施PRSA系统，以评估多药房儿童的用药情况- 相关问题。具体目标是：(1)进行一项回溯性队列研究，量化年度 多药房和与多药房升级相关的因素；(2)横断面评估 使用PRSA促进我们对信号噪声比和 信号检测挑战；以及(3)一项前瞻性队列研究，以评估在使用PRSA之前和 药物变化后检测到已知的不良反应。这一创新的提案可以提供证据来支持 更广泛地使用PRSA来评估具有医疗复杂性的脆弱儿童的其他治疗方法。

PROJECT SUMMARY/ABSTRACT An increasing number of children with medical complexity are exposed to polypharmacy in the ambulatory setting and take multiple high-risk medications daily. Polypharmacy can lead to serious adverse drug events (ADEs). The most vulnerable children with medical complexity exhibit a multitude of symptoms and have impairments that make the self-report of ADEs unfeasible, severely limiting the conduct of clinical trials and post-marketing drug surveillance studies to detect ADEs. Dr. James Feinstein’s overarching hypothesis is that repeated parent-reported symptom assessments (PRSA) before and after medication changes will provide clinically pertinent information, improve ADE signal detection, and enhance medication safety. This patient- oriented mentored career development award is designed to support the transition of James Feinstein, MD, MPH, an Assistant Professor of Pediatrics at the University of Colorado, into an independent clinician-scientist and to achieve his long-term career goal of becoming a national leader in pediatric polypharmacy and medication safety research. His short-term career goals are to (1) study factors involved in the escalation of polypharmacy and (2) implement a prospective PRSA system to guide and monitor pharmaceutical care for high-risk children. Dr. Feinstein will complete additional didactic and experiential training in 3 key areas necessary for his success: (1) pharmacoepidemiology and pharmacovigilance; (2) quantitative longitudinal data analysis; and (3) the design and conduct of prospective cohort studies. The University of Colorado Anschutz Medical Campus provides a unique research environment to conduct pediatric polypharmacy research, supported by collaborative research partnerships between the Adult and Child Consortium for Health Outcomes Research and Delivery Science (ACCORDS), The Skaggs School of Pharmacy and Pharmaceutical Sciences, and the Children’s Hospital Colorado Special Care Clinic for children with medical complexity. Dr. Feinstein’s renowned team of research mentors, Dr. Allison Kempe (health services research), Dr. Robert Valuck (pharmacoepidemiology), Dr. Chris Feudtner (children with complex chronic conditions), and Dr. Diane Fairclough (biostatistics), will guide completion of the proposed training and research plan. To achieve his short-term career goals, Dr. Feinstein proposes three research projects that will contribute to the implementation of a PRSA system to evaluate children with polypharmacy for medication- related issues. The specific aims are to conduct: (1) a retrospective cohort study to quantify annual polypharmacy and factors associated with escalation of polypharmacy; (2) a cross-sectional evaluation of symptoms in children with polypharmacy using PRSAs to advance our understanding of signal-to-noise and signal detection challenges; and (3) a prospective cohort study to assess whether using PRSAs prior to and after medication changes detects known ADEs. This innovative proposal could provide evidence to support the use of PRSA more broadly for the evaluation of other therapies in vulnerable children with medical complexity.