EHR-based Genomic Discovery and Implementation (Supplement)

基于 EHR 的基因组发现和实施（补充）

• 批准号: 10835712
• 负责人: Iftikhar J Kullo
• 金额: $ 18.88万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10835712
• 关键词: Administrative Supplement; Algorithms; Anxiety; Calibration; Classification; Clinical; Complex; Coronary heart disease; Data; Discrimination; Disease; Effectiveness; Employment; Environmental Risk Factor; Etiology; Future; Genetic; Genetic Risk; Genomics; Genotype; Healthcare; Individual; Insurance Coverage; Literature; Measures; Morbidity - disease rate; Odds Ratio; Outcome; Process; Quality of life; Randomized, Controlled Trials; Relative Risks; Research; Review Literature; Risk; Risk Assessment; Risk Estimate; Risk Factors; Science; Societies; Specificity; Stigmatization; Stress; Time; Update; care burden; clinical implementation; clinical risk; clinical translation; disorder risk; ethical, legal, and social implication; evidence base; hazard; health disparity; heart disease risk; improved; insight; mortality; polygenic risk score; preventive intervention; research clinical testing; risk prediction; risk stratification; screening; statistics; systematic review

PROJECT SUMMARY Estimating risk for common diseases is challenging because of their complex and multifactorial etiology. Common diseases pose an enormous health care burden, therefore even modest improvements in the accuracy of risk estimates could have a substantial impact. A promising avenue for refining risk stratification is to incorporate measures of genetic risk, clinical variables, and environmental factors, into comprehensive risk profiles. By providing orthogonal and incremental information, polygenic risk scores (PRS) could improve risk prediction for common diseases, which are collectively responsible for most of the mortality and morbidity worldwide. To inform use of PRS in the clinical setting there is need for an evidence base on the clinical utility of integrating PRS with other risk factors, for disease risk prediction. Randomized control trials to demonstrate the clinical utility of a PRS in prolonging survival or improving the quality of life, are generally infeasible, mainly because of time needed, significant expense, and the possibility that the PRS may need updating while the trials are still ongoing. In the absence of such trials, an analytical framework is needed to collect the appropriate evidence. As part of this administrative supplement application, we will conduct systematic evidence reviews assessing the state of the science on the clinical utility of PRS for common disease risk assessment, using coronary heart disease (CHD) as an example. Our systematic review will be based on the ACCE (analytic validity, clinical validity, clinical utility, and ethical, legal, and social implications) framework. Since analytic validity of genotyping is established, our focus is on the ‘..CCE’ components. The systematic reviews will collate evidence for the following: 1) clinical validity of PRS for CHD (PRSCHD); 2) clinical utility of using PRSCHD for risk assessment; including net reclassification improvement (NRI), integrated discrimination improvement (IDI), and change in outcomes (process, intermediate and clinical); 3) ethical, legal, social implications of using PRSCHD in the clinical setting.

项目摘要 估计普通疾病的风险由于其复杂和多因素的病因而具有挑战性。 常见疾病造成了巨大的医疗保健负担，因此甚至适度的改善 风险估计的准确性可能会产生重大影响。提炼风险分层的承诺途径是 将遗传风险，临床变量和环境因素的度量纳入综合风险 概况。通过提供正交和增量信息，多基因风险评分（PR）可以改善风险 对常见疾病的预测，这些疾病总体负责大多数死亡率和发病率 全世界。 要告知在临床环境中使用PRS 将PR与其他风险因素集成，以进行疾病风险预测。随机对照试验证明 PRS在延长生存或改善生活质量方面的临床实用性通常是不可行的，主要是 由于需要时间，大量费用以及PRS可能需要更新的可能性 试验仍在进行中。在没有此类试验的情况下，需要一个分析框架来收集 适当的证据。作为此行政补充申请的一部分，我们将进行系统 证据审查了评估PRS临床实用性科学状况的常见疾病风险的临床实用性 评估，以冠状动脉疾病（CHD）为例。我们的系统评价将基于 ACCE（分析有效性，临床有效性，临床效用以及道德，法律和社会影响）框架。 由于建立了基因分型的分析有效性，因此我们的重点是“ .. cce”成分。系统 评论将协作以下证据：1）PRS对CHD的临床有效性（PRSCHD）； 2）临床实用程序 使用PRSCHD进行风险评估；包括净重新分类改进（NRI），集成歧视 改进（IDI）和结果的变化（过程，中级和临床）； 3）道德，法律，社会 在临床环境中使用PRSCHD的含义。