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

项目摘要 在美国发现100万名家族性高胆固醇血症(FH)患者将导致减少 动脉粥样硬化性心血管疾病的发病率和死亡率。实现对人口健康的影响 识别患有这种遗传疾病的个体，进行系统的级联测试以识别所有受影响的高危人群 亲属也必须开始。然而，对指标患者的认识不足，以及对级联的摄取率低 检测，限制了潜在的人口健康影响。因此，这项提案将解决以下方面的关键差距 通过研究1)创新的指标患者识别方法 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)以患者为中心的家庭沟通援助方法的有效性 促进患者主动接受级联测试；以及3)这些的可行性、可接受性和成本 方法使用实施科学框架，以实现确定FH最佳实践的目标 识别和级联测试。这项研究是盖辛格和FH基金会的合作项目。我们 将利用Geisinger的MyCode®社区健康计划(MyCode)，这是一个链接到可用的EHR的生物库 对于研究，有20万名患者参与者登记参加了93,000个外显子组测序，其中有数十个 在这项研究的过程中，预计还会有数千人。在目标1中，我们将评估跳频识别方法， 包括两种基于表型的算法，这两种算法将应用于MyCode参与者的EHR。我们会 还要评估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预测值和阴性预测值。通过利用可用的关联性数据 通过MyCode，将对亲属的EHR数据进行高通量表型分析，以增强每个算法的表型 性能。在目标2中，我们将利用设计思维来开发新颖的、以患者为中心的家庭沟通。 和级联测试策略，以激活患者吸收级联测试，目标2的主要结果， 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 将在一项前瞻性的观察性比较有效性研究中提交给FH先证者。在《目标3》中， 在普罗科特实施研究概念模型的指导下，我们将评估实施成果 在系统、临床医生和患者层面创建综合FH护理模式。这将会实现的 通过定性研究，包括对FH患者、他们的高危亲属和FH的访谈和焦点小组 医疗保健提供者以及干预地图。收集的主要成果是可行性和 可接受性。还将进行微观成本分析，以告知成本影响。这些评估将告知 制定个人和个人均可接受的标准跳频识别和级联检测方案 卫生系统可以广泛传播，对个人的健康和福祉产生积极影响 患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.