Implementing and Evaluating Genetic Screening in Healthy Adults for Precision Public Health

在健康成人中实施和评估基因筛查以实现精准公共卫生

• 批准号: 10510602
• 负责人: Megan C. Roberts
• 金额: $ 42.08万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10510602
• 关键词: Address; Adoption; Adult; Apolipoproteins B; BRCA1 gene; BRCA2 gene; Caring; Characteristics; Clinical; DNA sequencing; Data; Development; Diagnosis; Disease; Effectiveness; Engineering; Ensure; Familial Hypercholesterolemia; Foundations; Future; Genes; Genetic; Genetic Diseases; Genetic Risk; Genetic Screening; Genomic medicine; Genomics; Goals; Guidelines; Health; Healthcare; Hereditary Breast and Ovarian Cancer Syndrome; Hereditary Nonpolyposis Colorectal Neoplasms; Hybrids; Individual; Interview; Knowledge; Learning; Life; MLH1 gene; MSH6 gene; Measures; Methods; Morbidity - disease rate; North Carolina; Outcome; PMS2 gene; Pathogenicity; Patient Outcomes Assessments; Patient-Focused Outcomes; Patients; Penetrance; Persons; Population; Population Genetics; Precision Health; Preventive Health Services; Process; Program Effectiveness; Program Sustainability; Public Health; Reporting; Research; Risk; Surveys; Testing; United States National Academy of Sciences; Universities; Work; base; clinically actionable; clinically relevant; cost; cost efficient; effectiveness evaluation; effectiveness study; follow-up; genetic variant; implementation barriers; implementation facilitators; implementation outcomes; implementation questions; improved; mortality; population health; precision medicine; prevent; preventive intervention; programs; satisfaction; screening; screening program; theories

Abstract In the US, millions of people unknowingly carry pathogenic genetic variants for Lynch syndrome (LS), Hereditary Breast and Ovarian Cancer (HBOC), and Familial Hypercholesterolemia (FH), which confer substantially-elevated risks of serious yet preventable diseases. For these genetic conditions, guideline- recommended preventive health services might reduce associated morbidity and mortality if knowledge of this underlying genetic risk is available. However, more than half of these individuals remain unidentified or are identified only after they or a significant number of relatives have been diagnosed with life-threatening diseases. This represents a missed opportunity to prevent disease. For this reason, National Academies of Sciences, Engineering and Medicine’s Genomics and Public Health Action Collaborative provided a roadmap for population genetic screening programs to improve identification of individuals with these clinically actionable conditions. Beginning June 2021, University of North Carolina (UNC) Program for Precision Medicine in Healthcare is piloting a clinical offering for genetics-based screening for the genes associated with LS, HBOC and FH, called the UNC Precision Health Genetic Screening Test. This clinical offering provides the ideal opportunity to study the implementation of a genetics-based screen program in a healthy population. To this end we propose to (1) examine implementation outcomes of the UNC Precision Health Genetic Screening Test; (2) identify and tailor strategies for the implementation of UNC Precision Health Genetic Screening Test; and (3) examine the impact of the UNC Precision Health Genetic Screening Test on patient outcomes. The objective of this proposal is to better understand and learn from the implementation of the UNC Precision Health Genetic Screening Test to inform implementation of precision health genetic screening in diverse, real- world clinical settings. Further, these findings will directly inform the development of future hypotheses to test the effect of the UNC Precision Health Genetic Screening Test on patient health outcomes and key implementation outcomes through a future Type II Hybrid Effectiveness study. Through this line of research, we can better understand the implementation and effectiveness of a genetics-based screening program. This foundational understanding will inform future work to achieve the promise of precision health for all.

摘要 在美国，数百万人在不知不觉中携带林奇综合征（LS）的致病性遗传变异， 遗传性乳腺癌和卵巢癌（HBOC）和家族性高胆固醇血症（FH）， 严重但可预防的疾病的风险大大增加。对于这些遗传性疾病，指南- 建议的预防性卫生服务可能会减少相关的发病率和死亡率，如果知识， 潜在的遗传风险。然而，其中一半以上的人仍然身份不明，或 只有在他们或相当数量的亲属被诊断出患有危及生命的疾病后， 疾病这意味着错过了预防疾病的机会。为此，美国国家科学院 科学，工程和医学的基因组学和公共卫生行动合作提供了一个路线图 用于群体遗传筛查计划，以提高对这些临床 可行的条件。从2021年6月开始，北卡罗来纳州大学（University of North Carolina）的精密计划 医疗保健中的医学正在试验一种临床产品，用于基于遗传学的筛查与以下疾病相关的基因： LS，HBOC和FH，称为“精确健康基因筛查测试”。该临床产品提供了 理想的机会，研究实施基于遗传学的屏幕程序在健康人群。到 为此，我们建议：（1）检查精准健康基因筛查的实施结果 （2）确定和定制实施精准健康基因筛查测试的策略; 和（3）检查的影响，精密健康基因筛查测试对病人的结果。的 本建议的目的是更好地理解和学习实施的“精确” 健康基因筛查测试，以告知在不同的，真实的实施精确的健康基因筛查- 世界临床环境。此外，这些发现将直接告知未来假设的发展，以测试 精准健康基因筛查测试对患者健康结果的影响， 通过未来的第二类混合有效性研究来实现成果。通过这一系列的研究， 我们可以更好地了解基于遗传学的筛查计划的实施和有效性。这 基本的了解将为今后实现人人享有精确健康的承诺的工作提供信息。