Identification Methods, Patient Activation, and Cascade Testing for FH: IMPACT-FH

项目摘要 在美国，识别出> 100万患有家族性高胆固醇血症（FH）的个体将导致降低 动脉粥样硬化性心血管疾病的发病率和死亡率。实现人口健康影响 识别具有这种遗传条件的个体，系统的级联测试以识别所有受影响的风险 亲戚也要开始。然而，索引患者的识别不足和级联反应的低吸收 测试，限制了潜在的人口健康影响。因此，本提案将解决这些关键差距， 通过研究1）创新的索引患者识别方法， 利用电子健康记录（EHR）数据的表型算法，以及下一代的基因组分析 测序数据; 2）以患者为中心的方法对家庭沟通援助的有效性， 促进患者对级联试验摄取的激活;以及3）这些的可行性、可接受性和成本 使用实施科学框架的方法，以实现定义FH最佳实践的目标 识别和级联测试。这项研究是Geisinger和FH基金会之间的合作。我们 将利用Geisinger的MyCode®社区健康倡议（MyCode），这是一个与EHR相关的生物银行， 用于研究，该研究有> 200，000名患者参与，其中约93，000名患者参与外显子组测序，其中数十名患者参与外显子组测序。 在这项研究的过程中，预计还会有数千人。在目标1中，我们将评估FH识别方法， 包括两种基于表型的算法，将应用于MyCode参与者的EHR。我们将 还评估了在同一队列中通过外显子组测序检测FH的能力，并将严格评估 比较每种方法的阳性和阴性预测值。利用现有的相关性数据， 通过MyCode，将对亲属的EHR数据进行高通量表型分析，以增强每个算法的 性能在目标2中，我们将利用设计思维开发新颖的、以患者为中心的家庭沟通 以及激活患者进行摄取级联试验的级联试验策略，这是Aim 2的主要结局， 这将通过Invitae的实验室记录和亲属的自我报告来衡量。这些新颖的方法 将在一项前瞻性、观察性比较有效性研究中向FH先证者提供。在目标3中， 在普罗克特的实施研究概念模型的指导下，我们将评估实施结果 在系统、临床医生和患者层面，创建综合FH护理模型。这将是完成 通过定性研究，包括FH患者、其高危亲属和FH的访谈和焦点小组， 医疗保健提供者以及干预映射。收集的主要成果是可行性和 可接受性还将进行微成本计算分析，以了解成本影响。这些评估将为 制定个人可接受的标准化FH识别和级联测试协议， 卫生系统，可以广泛传播，以积极影响个人的健康和福祉， FH的风险。

Project Summary Identifying the >1 million individuals with familial hypercholesterolemia (FH) in the U.S. will lead to reduced morbidity and mortality due to atherosclerotic cardiovascular disease. To achieve population health impact of identifying individuals with this genetic condition, systematic cascade testing to identify all affected at-risk relatives must also commence. However, both under-identification of index patients, and low uptake of cascade testing, limits the potential population health impact. Therefore, this proposal will address these critical gaps in translational cardiovascular medicine by studying 1) innovative index patient identification methods via both phenotypic algorithms that utilize electronic health record (EHR) data, and genomic analysis of next-generation sequencing data; 2) the effectiveness of patient-centered approaches for family communication assistance to promote patient activation toward cascade testing uptake; and 3) feasibility, acceptability, and cost of these methods using an implementation science framework towards the goal of defining best practices for FH identification and cascade testing. This study is a collaboration between Geisinger and The FH Foundation. We will utilize Geisinger's MyCode® Community Health Initiative (MyCode), a biobank linked to the EHR available for research, which has >200,000 patient-participants enrolled with exome sequencing on ~93,000, with tens of thousands more anticipated over the course of this study. In Aim 1, we will evaluate FH identification methods, including two phenotype-based algorithms, which will be applied to the EHR of MyCode participants. We will also assess the ability to detect FH through exome sequencing in the same cohort and will critically evaluate the comparative positive and negative predictive values of each method. By utilizing interrelatedness data available via MyCode, high-throughput phenotyping on relatives' EHR data will be performed to augment each algorithm's performance. In Aim 2, we will utilize design thinking to develop novel, patient-centered family communication and cascade testing strategies to activate patients to uptake cascade testing, the primary outcome of Aim 2, which will be measured by laboratory records from Invitae and by relatives' self-report. These novel approaches will be presented to FH probands in a prospective, observational comparative effectiveness study. In Aim 3, guided by Proctor's conceptual model for implementation research, we will evaluate implementation outcomes at the system, clinician, and patient levels to create a model for integrated FH care. This will be accomplished via qualitative research including interviews and focus groups of FH patients, their at-risk relatives, and FH healthcare providers as well as intervention mapping. The main outcomes to be collected are feasibility and acceptability. Microcosting analysis will also be performed to inform cost impact. These evaluations will inform the development of a standardized FH identification and cascade testing protocol acceptable to individuals and health systems that can be disseminated widely to positively impact the health and well-being of individuals at risk of FH.