Technology Enabled Strategies to Promote Treatment Adherence in Liver Transplant: The TEST Trial

项目摘要 在美国，肝硬化和终末期肝病（ESLD）的患病率在过去两年中几乎翻了一番。 几十年肝移植（LT）是ESLD的唯一救命选择，预计到2040年将增加23%。 LT需要大量的医疗资源，每年花费美国卫生系统267亿美元。是 在老年人中越来越多地进行;从2006年到2018年，65岁及以上的成年人增长最快 在移植等待名单上的年龄组。到2019年，70%的LTR是50岁及以上的成年人。的进步 免疫抑制（IS）和手术技术，平均5年后LT生存率现在超过70%。然而，在这方面， 维持最佳的、长期的肝移植功能和整体健康取决于适当地遵守 处方治疗。这可能是困难的，因为肝移植受者（LTR）与高方案竞争， 复杂性，平均服用11种有副作用的新药，需要频繁改变剂量。 由于移植前肝性脑病或其他原因，许多LTR具有挥之不去的认知障碍。 社会心理、经济或文化因素，这些因素都可能影响坚持治疗的能力。结果，第三个 的LTR显示对IS方案的依从性不足。粘附性差是肝移植的主要原因 排斥、肝衰竭、控制不良的医学合并症和随后的死亡。同样，不足 药物知识和无意的误用与移植后住院有关。尽管 由于依从性不足的负面和代价高昂的后果，很少有前瞻性的干预措施被 开发和测试，以优化服药行为和LT后的后续结果。然而， 在长期培训的背景下，有一些独特的考虑因素可以通过干预来加以利用：1）长期培训仍然是 无限期地连接到移植中心，以便利用一系列可用资源进行随访;护士协调员， 药剂师，心理和社会服务; 2）要有资格接受LT，患者必须有护理人员参与 提供LT后支持（但迄今为止还没有涉及护理人员的干预措施）。我们的主要目的是测试 技术支持的干预措施（TEST试验）改善治疗依从性和优化 在3个不同移植项目的360例新发LTR队列中，以患者为中心的临床结局 在费城，宾夕法尼亚州，芝加哥，伊利诺伊州和迈阿密，佛罗里达州。我们的干预利用现有的移植中心资源， 护理人员支持，以及广泛使用的以患者为中心的移动的健康工具，以远程监测LTR的 依从行为、“表型”依从问题，并针对这些问题定制移植中心的反应 性问题我们还计划评估干预保真度，使我们能够评估患者，护理人员，提供者 和卫生系统的障碍，以最佳的实施，以提高可扩展性。最后，我们将确定成本 从移植中心和医疗保健部门的角度来看，干预的成本效益。测试 试验将能够及时识别LTR依从性障碍的存在和性质， 移植中心和护理人员通过利用现有资源部署定制的解决方案，以优化健康。

PROJECT SUMMARY The prevalence of cirrhosis and end-stage liver disease (ESLD) in the U.S. has nearly doubled over the past two decades. Liver transplant (LT) is the only life-saving option for ESLD and is projected to increase 23% by 2040. LT requires considerable healthcare resources, costing the U.S. health system $26.7 billion annually. It is increasingly performed among older adults; from 2006 to 2018, adults 65 and older were the most rapidly growing age group on transplant waitlists. By 2019, 70% of LTRs were adults 50 and older. With advances in immunosuppression (IS) and surgical techniques, average 5-year post-LT survival now exceeds 70%. However, maintaining optimal, long-term liver graft function and overall health are contingent upon proper adherence to prescribed treatment. This can be difficult, as liver transplant recipients (LTRs) contend with high regimen complexity, taking on average 11 new medications that have side effects and require frequent dosage changes. Many LTRs have lingering cognitive impairments due to pre-transplant hepatic encephalopathy, or other psychosocial, financial, or cultural factors that all can affect the ability to adhere to treatment. As a result, a third of LTRs demonstrate inadequate adherence to IS regimens. Poor adherence is a leading cause of liver graft rejection, liver failure, poorly controlled medical comorbidities and subsequent mortality. Similarly, inadequate medication knowledge and unintentional misuse are associated with post-transplant hospitalizations. Despite the negative and costly consequences of inadequate adherence, very few prospective interventions have been developed and tested to optimize medication-taking behaviors and subsequent outcomes post-LT. However, there are unique considerations within the context of LT that can be leveraged by interventions: 1) LTRs remain indefinitely connected to transplant centers for follow-up with a range of available resources; nurse coordinators, pharmacists, psychological and social services; 2) to be eligible for LT, patients must have involved caregivers to provide post-LT support (yet no interventions to date have involved caregivers). Our primary aim is to test the effectiveness of a technology-enabled intervention (TEST trial) to improve treatment adherence and optimize patient-centered and clinical outcomes among a cohort of 360 de novo LTRs at 3 diverse transplant programs in Philadelphia, PA, Chicago, IL, and Miami, FL. Our intervention leverages existing transplant center resources, caregiver support, and widely available patient-centered mobile health tools to remotely monitor LTRs' adherence behaviors, `phenotype' adherence concerns, and tailor transplant center responses to those concerns. We additionally plan to assess intervention fidelity, enabling us to evaluate patient, caregiver, provider and health-system barriers to optimal implementation to enhance scalability. Finally, we will determine the costs and cost-effectiveness of the intervention from a transplant center and healthcare sector perspective. The TEST trial will enable the timely identification of the presence and nature of LTR adherence barriers and mobilize transplant centers and caregivers to deploy tailored solutions by leveraging existing resources to optimize health.