Comparative Effectiveness Research in Axial Spondyloarthritis

项目摘要 这项提议将为王润生博士提供必要的重要培训，以实现她的长期目标 成为轴性脊柱炎比较疗效研究的独立临床研究员 (AxSpA)，其整体研究计划旨在优化AxSpA患者的临床管理 以及改善AxSpA的结果。 可用于指导临床医生和患者制定个性化治疗计划的证据有限 关于当前治疗药物的组级有效性和安全性数据。传统的正面交锋 随机临床试验受到研究臂数少、成本高以及无法测量的限制 个体化治疗效果。N-of-1试验使用多交叉来解决患者与治疗之间的相互作用，并 衡量个体对不同疗法的反应。生物医学信息学的最新进展使它 有可能将日常临床护理转变为设计精良的n-of-1试验。一种基于电子病历的可计算器 表型算法将改进队列识别并降低患者招募的复杂性 在这样的审判中。因此，我假设1中N试验将确定最有效的治疗方法 用于个人症状控制的药物。在长期、务实、大规模的N-of-1试验中， 提供机会研究不同药物在现实世界中的比较有效性。 创新的试验设计和生物信息学工具将用于队列识别和系统数据收集 除其他外，促进AxSpA未来比较有效性研究的关键要素。 这项提案的总体目标是测试在axSpA中对两种非甾体抗炎药进行N-of-1试验的可行性，并开发 为在更大范围内规划和实施这类试验提供便利的信息学工具。建议数 一系列N-of-1试验将提供一个框架，用于比较其他治疗药物在 有AxSpA的患者。再加上基于EHR的队列识别工具，这项试验设计将增加 患者个体化精准治疗，促进以患者为中心的研究和个性化医疗 在axSpA。

PROJECT ABSTRACT This proposal will provide Dr. Runsheng Wang with the vital training needed to achieve her long-term goal of becoming an independent clinical investigator in comparative effectiveness research in axial spondyloarthritis (axSpA), with an overall research program aimed at optimizing clinical management of patients with axSpA and improving axSpA outcomes. Limited evidence is available to guide clinicians and patients to make an individualized treatment plan based on current group level effectiveness and safety data of therapeutic agents. Traditional head-to-head randomized clinical trials are limited by small number of study arms, high cost, and inability to measure individual treatment effects. N-of-1 trials use multi-crossover to address patient-treatment interaction and to measure individual responses to different therapies. Recent advances in biomedical informatics make it possible to transform everyday clinical care to robust well designed n-of-1 trials. An EHR-based computable phenotyping algorithm would improve cohort identification and reduce the complexity of patient recruitment during such trials. Therefore, I hypothesize that N-of-1 trials would identify the most effective therapeutic agents for symptom control in individuals. In the long-term, pragmatic, large scale N-of-1 trials would provide the opportunity to study comparative effectiveness of different drugs in the real world setting. Innovative trial design and bioinformatics tools for cohort identification and systemic data collection will be key elements, among others, in facilitating future comparative effectiveness research in axSpA. The overall goal of this proposal is to test the feasibility of N-of-1 trials of two NSAIDs in axSpA and to develop informatics tools to facilitate the planning and implementation of such trials in a larger scale. The proposed series of N-of-1 trials will provide a framework for comparative effectiveness of other therapeutic agents in patients with axSpA. Coupled with an EHR-based cohort identification tool, this trial design will increase therapeutic precision in individual patients and promote patient-centered research and personalized medicine in axSpA.