eMERGE Phase IV Clinical Center at Mass General Brigham

麻省总医院布里格姆分校 eMERGE IV 期临床中心

• 批准号: 10625354
• 负责人: ELIZABETH W KARLSON
• 金额: $ 116.7万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10625354
• 关键词: Algorithms; All of Us Research Program; Asian; Atrial Fibrillation; Benchmarking; Bioinformatics; Black race; Clinical; Clinical Data; Colorectal Cancer; Communication; Complex; Computerized Medical Record; Consent; Coronary Arteriosclerosis; Data; Data Set; Development; Disclosure; Disease; Disease Outcome; Electronic Health Record; Electronic Medical Records and Genomics Network; Electronics; Ethnic Origin; Family; Fast Healthcare Interoperability Resources; Genetic Risk; Genomics; Genotype; Glycosylated hemoglobin A; Goals; Grant; Harm Reduction; Health Personnel; Healthcare; Hispanic; Individual; Information Technology; Intervention; Japan; Laboratories; Leadership; Life Style; Link; Low-Density Lipoproteins; Major Depressive Disorder; Medical; Medicine; Mental Depression; Methods; New England; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Outcome and Process Assessment; Participant; Patient-Focused Outcomes; Patients; Performance; Pharmaceutical Preparations; Phase; Phenotype; Physical activity; Physicians; Population Heterogeneity; Predictive Value; Preventive; Preventive therapy; Process; Random Allocation; Recommendation; Recording of previous events; Reporting; Risk; Risk Assessment; Risk Factors; Risk Reduction Behavior; Statistical Methods; Surveys; Testing; Training; Trans-Omics for Precision Medicine; Veterans; Visit; behavioral outcome; biobank; clinical care; clinical center; clinical decision support; clinical implementation; clinical practice; clinical research site; clinical risk; design; economic outcome; ethical, legal, and social implication; evidence based guidelines; exome; experience; genetic analysis; genome resource; genome wide association study; health care service utilization; high risk; high risk population; insight; machine learning algorithm; multi-ethnic; novel; polygenic risk score; portability; primary outcome; programs; psychiatric genomics; recruit; risk stratification; screening; support tools; trait

Abstract: To enable the application of PRS development and implementation, our eMERGE IV proposal from Partners HealthCare leverages a large biobank (>105,000 consented with genotype data on 40,000), clinical data in the electronic health records (EHR) for >4 million patients from the largest integrated health care provider in New England, advanced bioinformatics expertise, prior leadership in PRS development and state- of-the-art genetic analysis, established expertise in returning genomics results, and experience using information technology to transform clinical processes and assessing outcomes. We propose to build on our expertise to accomplish the specific aims: Aim 1 (Discovery): Hypothesis: Polygenic risks scores will allow us to stratify eMERGE subjects based on genetic risk for common complex traits. Using the largest available genomic data resources, we will calculate and validate new PRS for coronary artery disease, atrial fibrillation, type 2 diabetes, colorectal cancer and major depression across diverse ancestries. We will 1) compare and benchmark the performance of existing PRS construction methods in different ancestral groups, 2) develop novel statistical methods for robust trans-ethnic PRS prediction, and integrate PRS with established clinical risk factors and family history. We will obtain PRS from our network colleagues for an additional 15-e- phenotypes (total 20) with a goal of identifying high-risk individuals, e.g., top 2% of PRS risk Aim 2 (RiskInsight Report/ELSI): We will develop a “Risk Insight Report” with clinical risk factors, family history, and PRS with evidence-based recommendations for high risk participants (top 2% of phenotype specific PRS distribution) for electronic clinical implementation. We will assess risk communication formats in our ELSI Sub-Aim 1: To test the impact and interpretability of two mock RiskInsight Reports summarizing PRS as either (a) dichotomous (defining the patient as high-risk vs intermediate/low risk) or (b) quantitative (providing a numerical estimate of the percentile of risk for the patient), with linked clinical recommendations in both cases. We will then assess, through surveys of diverse HCPs and patients, the extent to which the mock reports are understood by both HCPs and patients. Aim 3 (Outcomes): Hypothesis: Physicians will alter their surveillance and treatment of patients based on eCDS of RiskInsight Reports. Among HCPs for high-risk subjects, we will see at least one change in clinical care after disclosure discussions with subjects. We will recruit 2500 participants for implementation of clinical PRS in RiskInsight Reports using a SMART on FHIR app for eCDS integrated with the EHR. The primary outcome will be whether any HCP took any action within 12 months after receipt of e-CDS defined by ordering screening tests, prescribing a preventive medication, or providing lifestyle advice. We will conduct analyses of the effect of disclosing results to high risk participants to determine how personalized results changed patient outcomes in laboratory values, risk reduction behaviors, or health care utilization.

摘要：为了实现 PRS 开发和实施的应用，我们的 eMERGE IV 提案来自 Partners HealthCare 利用大型生物库（超过 105,000 人同意，其中 40,000 人的基因型数据）、临床 来自最大的综合医疗保健机构的超过 400 万患者的电子健康记录 (EHR) 数据 新英格兰的提供商，先进的生物信息学专业知识，在 PRS 开发和状态方面的先前领导地位 最先进的遗传分析、返回基因组学结果的成熟专业知识以及使用的经验 信息技术来改变临床流程和评估结果。我们建议以我们的 实现特定目标的专业知识： 目标 1（发现）：假设：多基因风险评分将 允许我们根据常见复杂性状的遗传风险对 eMERGE 受试者进行分层。使用 最大的可用基因组数据资源，我们将计算和验证冠状动脉疾病的新 PRS， 不同血统的心房颤动、2 型糖尿病、结直肠癌和重度抑郁症。我们将 1) 比较和基准不同祖先群体中现有 PRS 构建方法的性能， 2) 开发新的统计方法来进行稳健的跨种族 PRS 预测，并将 PRS 与已建立的 临床危险因素和家族史。我们将从我们的网络同事那里获得额外的 15-e- PRS 表型（共 20 种），目标是识别高风险个体，例如 PRS 风险最高的 2% 目标 2 （RiskInsight Report/ELSI）：我们将制定一份“风险洞察报告”，其中包含临床风险因素、家庭 病史和 PRS，为高风险参与者（前 2%）提供基于证据的建议 表型特异性 PRS 分布）用于电子临床实施。我们将评估风险 我们的 ELSI 子目标 1 中的通信格式：测试两个模拟的影响和可解释性 RiskInsight 报告将 PRS 总结为 (a) 二分法（将患者定义为高风险 vs 中/低​​风险）或（b）定量（提供患者风险百分位数的数值估计）， 两种情况下都附有相关的临床建议。然后，我们将通过对不同 HCP 的调查来评估 患者和医护人员对模拟报告的理解程度。目标 3（成果）： 假设：医生将根据 eCDS 改变对患者的监测和治疗 风险洞察报告。在高风险受试者的 HCP 中，我们将看到临床方面至少发生一项变化 与受试者进行披露讨论后的护理。我们将招募2500名参与者来实施 RiskInsight 报告中的临床 PRS 使用 SMART on FHIR 应用程序，用于与 EHR 集成的 eCDS。这 主要结果是任何 HCP 是否在收到 e-CDS 后 12 个月内采取了任何行动，定义为 安排筛查测试、开预防性药物或提供生活方式建议。我们将进行 分析向高风险参与者披露结果的效果，以确定如何个性化结果 改变了患者在实验室值、降低风险行为或医疗保健利用方面的结果。