Rational Integration of Polygenic Risk Scores (RIPS)

多基因风险评分的合理整合 (RIPS)

基本信息

批准号：
10589785
负责人：
Jing Hao
金额：
$ 95.53万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-03-10 至 2027-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10589785
关键词：
Address Adopted Affect Age Algorithms Area Atherosclerosis Caring Clinical Colorectal Cancer Complex Costs and Benefits Data Data Analyses Decision Modeling Development Disease Disparity Economic Models Effectiveness Environment Epidemiology Equity Foundations Funding Genomic medicine Genomics Growth Health Heart Diseases Hereditary Breast and Ovarian Cancer Syndrome Hereditary Nonpolyposis Colorectal Neoplasms Hyperlipidemia Intervention Investments Mendelian disorder Modeling Outcome Patient Care Patient-Focused Outcomes Performance Population Population Heterogeneity Prevalence Preventive care Preventive measure Publishing Research Research Priority Review Literature Risk Risk Assessment Risk Reduction Techniques Testing Uncertainty Underrepresented Populations Underserved Population United States National Institutes of Health Work clinical outcome assessment clinical risk cost cost effective cost effectiveness disorder risk economic impact economic value gene therapy genetic testing high risk improved malignant breast neoplasm new technology novel polygenic risk score precision medicine programs screening

项目摘要

Project Summary There has been extraordinary growth in new techniques to predict common, complex disease based on polygenic risk scores (PRS). Without an understanding grounded in evidence, it is unlikely that the clinical use of PRS will propagate from highly specialized applications and environments to become adopted more broadly and provide greater benefit to the US population. Critical challenges include: 1) understanding the impact of clinical PRS for multiple diseases on long-term patient outcomes, 2) identifying risk thresholds for return of results that optimize patient outcomes and provide cost-effective care, 3) understanding how PRS performance across diverse populations may affect existing disparities and subsequent patient outcomes. We propose to address these challenges using decision analytic modeling and by building on our extensive work in this area to create a novel framework capable of assessing PRSs in the context of monogenic and clinical risks. We have already created clinical-economic models to project lifetime clinical impact and cost-effectiveness for population-level genomic screening with return of monogenic disease risks associated with three CDC Tier 1 conditions: hereditary breast and ovarian cancer, Lynch syndrome, and familial hyperlipidemia. As part of this proposal, titled Rational Integration of Polygenic Risk Scores (RIPS), we will create models to assess the clinical outcomes and economic value of population screening using PRS in real- world settings and applied to large and diverse populations. The Aims of the proposal include 1) to evaluate published and real-world evidence on the clinical value of adding PRS to inform comprehensive genomic risk assessment; 2) to understand the impact of PRS performance and return risk thresholds on incremental clinical benefit and cost effectiveness for breast cancer, atherosclerotic cardiovascular disease, and colorectal cancer, and 3) to develop research priorities for the equitable development and implementation of PRS across underserved and underrepresented populations.

项目摘要新技术已经有非凡的增长来预测常见的复杂疾病基于多基因风险评分（PRS）。没有任何理解以证据为基础，那是 PRS的临床使用不太可能从高度专业的应用程序中传播环境更广泛地采用并为美国提供更大的好处人口。关键挑战包括：1）了解临床PR对多重的影响长期患者预后的疾病，2）确定结果的风险阈值以返回结果优化患者的结果并提供具有成本效益的护理，3）了解PRS 跨不同人群的表现可能会影响现有差异和随后的患者结果。我们建议使用决策分析建模和通过建立我们在这一领域的广泛工作，以创建一个能够评估的新型框架 PRS在单基因和临床风险的背景下。我们已经创建了临床经济学投射终身临床影响和人群基因组的成本效益的模型筛查与三种CDC第1条条件相关的单基因疾病风险的回归：遗传性乳腺癌和卵巢癌，林奇综合征和家族性高脂血症。作为该提议标题为“多基因风险评分（RIPS）的合理整合”，我们将创建模型评估使用PRS中的人口筛查的临床结果和经济价值世界环境，应用于大型和多样化的人群。提案的目的包括 1）评估已发布的和现实世界的证据，添加PR的临床价值以告知全面的基因组风险评估； 2）了解PRS性能的影响并以增量临床益处和乳房的成本效益回报风险阈值癌症，动脉粥样硬化心血管疾病和大肠癌，以及3）对公平开发和实施PRS的研究重点服务不足和代表性不足的人群。