Using real-world evidence to define safe pain management strategies in cirrhosis

项目概要/摘要 高达80%的肝硬化患者经历疼痛，这一比例是普通人群的两倍。 然而，由于供应商对不良事件的担忧，肝硬化患者的疼痛管理具有独特的挑战性 与多种类型的止痛药有关，这不幸地使这些患者处于治疗不足的风险中。 痛苦临床上关于实际疼痛管理策略和镇痛相关危害的数据有限。 不同人群的肝硬化患者，因此，关于如何 适当地治疗这一人群的疼痛。本提案的目的是解决这一关键的未得到满足的问题 通过调查患者中常用镇痛药的实际使用和危害， 肝硬化告知循证指南的发展，以支持供应商在管理疼痛， 人口在KL 2的支持下，鲁宾博士创建了一个超过50万退伍军人的回顾性纵向队列 使用国家退伍军人健康管理局（VHA）电子健康记录（EHR）数据。她 将利用这一队列来实现以下目标：（1）定义疼痛管理的流行病学， 肝硬化镇痛相关不良后果的发生率和风险因素;（2）量化主要并发症的风险 镇痛药使用者与非使用者的不良结局;（3）建立提供证据的指导原则- 通过德尔菲共识过程对肝硬化患者进行基于疼痛的管理。这项工作将提供 为未来的务实试验提供必要的初步数据，以测试本指南的传播对 提供者的做法和病人的结果和生活质量。鲁宾博士是进行这项研究的唯一人选 作为加州大学旧金山弗朗西斯科的肝病学家，他具有研究临床结果的经验， 包括疼痛和止痛药的使用。建立在坚实的基础上 这项K23奖将使鲁宾博士成为一名独立的卫生服务研究人员， 在生成和翻译真实的的四种基本技能方面为她提供了正式的培训和经验- 全球证据：（1）有效利用基于EHR的大型数据集，（2）药物流行病学分析，（2） 因果推理方法;（4）将证据转化为临床实践的技术。她有 组建了一个多学科导师团队，具有肝病学和临床结局研究方面的专业知识 （Jennifer Lai），利用观察数据的生物统计学和流行病学技能（Salomeh Keyhani），以及 疼痛管理和实施前/实施方法（Karen Seal）。她的科学顾问会 提供先进生物统计方法（Charles McCulloch）的额外方法学专业知识，基于VHA 流行病学研究设计（凯瑟琳Hoggatt）和德尔菲共识方法（丽贝卡Sudore）。的 建议的多学科团队，科学目标和职业发展目标不仅会促进鲁宾博士的 过渡到一个成功的独立调查员和卫生服务领域的研究领导者， 这不仅可以改善肝脏病学，而且更重要的是，可以改善对患有疼痛的肝硬化患者的护理。

PROJECT SUMMARY / ABSTRACT Up to 80% of patients with cirrhosis experience pain—a rate that is twice as high as in the general population. Yet managing pain in cirrhosis patients is uniquely challenging due to provider concerns about adverse events related to multiple classes of analgesics, which unfortunately puts these patients at risk for undertreatment of pain. There are limited data on actual pain management strategies and analgesic-related harms in the clinically diverse population of cirrhosis patients, and consequently, minimal evidence-based guidance on how to appropriately treat pain in this population. The objective of the current proposal is to address this critical unmet need by investigating real-world utilization and harms of commonly used analgesics among patients with cirrhosis to inform the development of evidence-based guidance to support providers in managing pain in this population. With KL2 support, Dr. Rubin has created a retrospective longitudinal cohort of >500,000 Veterans with cirrhosis using national Veterans Health Administration (VHA) electronic health record (EHR) data. She will leverage this cohort to achieve the following Aims: (1) Define the epidemiology of pain management, and rates of and risk factors for analgesic-related adverse outcomes in cirrhosis; (2) Quantify the risk of major adverse outcomes in analgesic users versus nonusers; (3) Establish guiding principles for providing evidence- based pain management to cirrhosis patients through a Delphi consensus process. This work will provide essential preliminary data for a future pragmatic trial to test the impact of dissemination of this guidance on both provider practices and patient outcomes and quality-of-life. Dr. Rubin is uniquely positioned to conduct this study as a hepatologist the at the University of California, San Francisco with experience studying clinical outcomes, including pain and analgesic use, in cirrhosis patients using large datasets. Building upon a strong foundation of research support, this K23 award will establish Dr. Rubin as an independent health services researcher by providing her with formal training and experience in four essential skills for generating and translating real- world evidence: (1) effectively leveraging large EHR-based datasets, (2) pharmacoepidemiologic analysis, (2) causal inference methods, and (4) techniques for translating evidence into clinical practice. She has assembled a multidisciplinary mentorship team with expertise in hepatology and clinical outcomes research (Jennifer Lai), biostatistical and epidemiologic skills for leveraging observational data (Salomeh Keyhani), and pain management and pre-implementation/implementation methods (Karen Seal). Her scientific advisors will provide additional methodologic expertise in advanced biostatistical methods (Charles McCulloch), VHA-based epidemiologic study design (Katherine Hoggatt), and Delphi consensus methods (Rebecca Sudore). The proposed multidisciplinary team, scientific aims, and career development goals will not only foster Dr. Rubin's transition to a successful independent investigator and health services research leader within the field of hepatology, but also, more importantly, improve the care delivered to cirrhosis patients suffering from pain.