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: 10207715
• 负责人: ELIZABETH W KARLSON
• 金额: $ 141.56万
• 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/10207715
• 关键词: Algorithms; All of Us Research Program; Asians; Atrial Fibrillation; Benchmarking; Bioinformatics; 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; Family; Fast Healthcare Interoperability Resources; Genetic Risk; Genomics; Genotype; Glycosylated hemoglobin A; Goals; Grant; Harm Reduction; Health Personnel; Healthcare; Hispanics; 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; Participant; Patient-Focused Outcomes; Patients; Performance; Pharmaceutical Preparations; Phase; Phenotype; Physical activity; Physicians; Population Heterogeneity; Predictive Value; Preventive; Preventive therapy; Process; Recommendation; Recording of previous events; Reporting; Risk; Risk Factors; Risk Reduction Behavior; Statistical Methods; Surveys; Testing; Training; Trans-Omics for Precision Medicine; Veterans; Visit; base; behavioral outcome; biobank; clinical care; clinical center; clinical decision support; clinical implementation; clinical practice; clinical research site; clinical risk; data resource; design; economic outcome; ethical legal social implication; evidence based guidelines; exome; experience; genetic analysis; genome wide association study; genomic data; health care service utilization; high risk; 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，我们从 Partners Healthcare利用大型生物库（> 105,000个同意了40,000的基因型数据），临床 电子健康记录中的数据（EHR）中，来自最大综合医疗保健的400万患者 新英格兰的提供商，高级生物信息学专业知识，PRS开发领域的先前领导和州 - 在遗传分析中，建立了归还基因组学结果的专业知识，并使用经验 信息技术改变临床过程并评估结果。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：分数将 允许我们根据共同复杂性状的遗传风险对出现的受试者进行分层。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PR， 房颤，2型糖尿病，结直肠癌和大型祖先的重大抑郁症。我们将1） 比较和基准在不同祖先组中现有PRS构造方法的性能， 2）开发用于鲁棒跨种族PRS预测的新型统计方法，并将PR与已建立 临床风险因素和家族史。我们将从我们的网络同事那里获得PRS，以额外15-e- 表型（总计20），目的是识别高风险个体，例如PRS风险的前2％AIM 2 （风险企业报告/ELSI）：我们将开发一个“风险洞察报告”，该报告具有临床风险因素，家庭 历史以及对高风险参与者提供基于证据的建议的PR（最高的2％ 用于电子临床实施的表型特异性PR分布）。我们将评估风险 我们的Elsi Sub-aim 1：测试两个模拟的影响和解释性 风险视觉报告总结为（a）二分法的PRS（将患者定义为高风险与 中等/低风险）或（b）定量（提供对患者风险百分比的数值估计）， 在这两种情况下都有链接的临床建议。然后，我们将通过对潜水员HCP和 患者，HCP和患者都了解模拟报告的程度。 AIM 3（结果）： 假设：医师将根据ECD的ECD改变患者的监视和治疗 Riskinsight报告。在高危受试者的HCP中，我们将看到临床至少发生变化 与受试者进行披露后的讨论。我们将招募2500名参与者实施 风险视觉报告中使用SMART在FHIR应用程序上与EHR集成的ECD的临床PRS报告。这 主要结果将是在收到由E-CD定义的E-CD后的12个月内采取任何措施 订购筛查测试，开处方预防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影响，以确定个性化结果 改变了实验室价值，降低风险行为或医疗保健利用的患者预后。