Comparative Risks and Benefits of Pharmacological Therapies for Older Patients with Inflammatory Bowel Diseases

项目总结/摘要 老年人（≥ 65岁）炎症性肠病（IBD）的患病率正在上升， 以证据为基础的指导来治疗这些老年人。在老年多发病患者中，治疗 决策不仅应考虑疾病并发症的风险，还应考虑治疗并发症和非IBD， 肠外并发症因此，为了告知最佳治疗方法，全面评估 不同疗法对所有这些结果的比较效果是必要的。现有单中心 观察性研究受到样本量小的限制，由于医疗保健分散而缺失数据， 而基于行政索赔的研究由于缺乏详细的临床数据而受到限制;这些限制可以 通过连接两个数据源来克服。在这个以病人为导向的指导职业发展奖中 Siddharth Singh博士建议：（目标1.1）描述疾病负担和治疗模式， (Aim#1.2）使用以下指标评估和预测死亡、疾病、治疗和肠外并发症的风险 机器学习算法和（目标#2.1）比较不同的总体有效性和（目标#2.2）安全性 老年IBD患者的治疗策略。这将使用一个高度创新的信息为基础的研究 在一个多中心、基于电子病历（EMR）的老年IBD患者队列中， 相应的医疗保险索赔。基于EMR的队列将有助于表型和疾病严重程度 评估，以及与医疗保险索赔的联系将增加风险暴露和结果确定，克服 医疗保健分散和短期随访的挑战。核心假设是，老年人 与年轻人相比，具有系统性不同的风险特征，使用生物单药治疗更安全， 与长期单独使用皮质类固醇相比，治疗IBD的更有效方法，非生物制剂 免疫调节剂单一疗法以及生物制剂和免疫调节剂的组合疗法。获得 pSCANNER（以患者为中心的可扩展国家有效性网络）的先进基础设施 研究），13个PCORI资助的临床数据研究网络之一，以及整个医疗保险数据库，在一个 在UCSD的高度支持和有利的环境，与跨学科的指导，由一个合作 来自不同背景的经验丰富的导师和顾问团队（临床信息学，比较 有效性研究，IBD治疗学）是该应用的关键优势。除了直接通知临床 实践上的治疗方法，在老年患者的IBD，这一建议将提高职业生涯的 候选人通过提供独特的技能，在应用临床信息学，隐私保护记录链接 技术，预测分析和比较有效性研究，并创建一个多机构，EMR- 基于特征明确的IBD患者队列，与医疗保险索赔相关。这最终将有助于 候选人的长期目标是建立一个独立的IBD研究生涯，重点是比较 有效性研究和人口健康管理使用新的信息为基础的方法。

PROJECT SUMMARY/ABSTRACT The prevalence of inflammatory bowel diseases (IBD) in older adults (≥65y) is rising, and there is limited evidence-based guidance on treating these older adults. In older patients with multi-morbidity, treatment decisions should factor in not only risk of disease complications, but also treatment complications and non-IBD, extra-intestinal complications. Hence, to inform optimal treatment approach, a comprehensive assessment of comparative effects of different therapies on all of these outcomes is warranted. Existing single-center observational studies are limited by small sample size, and missing data due to fragmented health care, whereas administrative claims-based studies are limited by lack of detailed clinical data; these limitations can be overcome by linking the two data sources. In this patient-oriented mentored career development award proposal, Dr. Siddharth Singh proposes to: (Aim #1.1) characterize disease burden and treatment patterns, (Aim #1.2) assess and predict risks of death, disease, treatment and extra-intestinal complications using machine-learning algorithms and (Aim #2.1) compare overall effectiveness and (Aim #2.2) safety of different treatment strategies in older patients with IBD. This will be studied using a highly innovative informatics-based approach in a multi-site, electronic medical record (EMR)-based cohort of older patients with IBD, linked to their corresponding Medicare claims. The EMR-based cohort will facilitate phenotyping and disease severity assessment, and linkage to Medicare claims will augment exposure and outcome ascertainment, overcoming challenges of fragmentation of healthcare and short follow-up. The central hypothesis is that, that older adults have systematically different risk profiles than younger adults, and using biologic monotherapy is a safer and more effective approach to treating IBD, as compared to using long-term corticosteroids alone, non-biologic immunomodulator monotherapy, and combination therapy of biologics and immunomodulators. The access to the advanced infrastructure of pSCANNER (Patient-centered Scalable National Network for Effectiveness Research), one of 13 PCORI-funded Clinical Data Research Networks, and entire Medicare database, in a highly supportive and conducive environment at UCSD, with cross-disciplinary mentorship by a collaborative and experienced team of mentors and advisors from diverse backgrounds (clinical informatics, comparative effectiveness research, IBD therapeutics) is a key strength of this application. Besides directly informing clinical practice on treatment approaches in older patients with IBD, this proposal will enhance the career of the candidate by providing unique skills in applied clinical informatics, privacy-preserving record linkage techniques, predictive analytics, and comparative effectiveness research, and create a multi-institutional, EMR- based cohort of well-characterized IBD patients, linked with Medicare claims. This will ultimately contribute to the candidate's long-term goal of establishing an independent IBD research career focusing on comparative effectiveness research and population health management using novel informatics-based approaches.