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.

项目概要预测常见、复杂疾病的新技术取得了惊人的发展基于多基因风险评分（PRS）。如果没有基于证据的理解， PRS 的临床应用不太可能从高度专业化的应用中传播出来，并且环境得到更广泛的采用并为美国提供更大的利益人口。关键挑战包括：1）了解临床 PRS 对多种疾病的影响疾病对长期患者结果的影响，2) 确定返回结果的风险阈值，优化患者治疗效果并提供具有成本效益的护理，3) 了解 PRS 如何不同人群的表现可能会影响现有的差异和随后的患者结果。我们建议使用决策分析模型来解决这些挑战以我们在这一领域的广泛工作为基础，创建一个能够评估的新颖框架单基因和临床风险背景下的 PRS。我们已经创建了临床经济预测人群水平基因组的终生临床影响和成本效益的模型筛查与 CDC 三种 1 级病症相关的单基因疾病风险回归：遗传性乳腺癌和卵巢癌、林奇综合征和家族性高脂血症。作为一部分这个提案名为多基因风险评分的理性整合（RIPS），我们将创建模型评估使用 PRS 进行人群筛查的临床结果和经济价值世界环境并适用于大量不同的人群。该提案的目标包括 1) 评估已发表的和真实世界的证据，说明添加 PRS 的临床价值全面的基因组风险评估； 2）了解PRS性能的影响以及关于乳腺增量临床效益和成本效益的返回风险阈值癌症、动脉粥样硬化性心血管疾病和结直肠癌，以及 3) 发展跨地区公平发展和实施 PRS 的研究重点服务不足和代表性不足的人群。