Exome sequencing in Diverse Populations in Colorado & Oregon

项目总结/摘要：需要进行更多的研究，以确定如何改善 患者和提供者了解、交流并选择使用外显子组测序， 指导医疗决策。这些挑战在识字率有限的人口中进一步加剧， 有意义地理解结果或根据结果采取行动的其他障碍。为了解决这些问题，该项目将 招募60%以上的不同种族、民族和社会经济背景的患者。拟议的项目是一个 延长我们的CSER 1项目的携带者检测，因为这两个项目都涉及筛查健康人， 综合卫生系统，使独特的机会，以评估下游的卫生保健决策。 利用通过CSER 1获得的利益相关者投入，项目目标是实施一个遗传性的 癌症风险评估计划在健康的18-50岁的人在初级保健设置垂直 综合保健服务系统（Kaiser Permanente）和一个联邦合格的保健中心（Denver Health） 并将外显子组测序对1100名患者和寻求常规治疗的患者的影响进行比较。项目 将重点关注遗传性乳腺癌和卵巢癌以及Lynch综合征， 癌症预防的临床建议。我们将评估：1）外显子组测序的实施， 解释; 2）量身定制的互动，包括情境化的同意过程，一种新的决策辅助工具， 选择附加结果的可选类别，以及修改后的结果披露方法， 遗传咨询; 3）医疗口译工具（互动式网络教育）和初级保健 提供者（电子健康管理工具）; 4）临床效用（医疗保健利用率和对 推荐的护理）和来自外显子组测序的主要和附加结果的个人效用; 5） 该计划的成本;以及6）考虑基因组的个人效用的伦理和政策影响 关于医疗保险决定的信息。这个经验丰富的团队在CSER 1中工作效率很高 并有能力成功地进行拟议的研究，具有遗传学方面的专业知识， 流行病学，医学遗传学，健康通讯，健康信息学，经济学，人类学， 生物统计学和生物伦理学。我们将与包括患者、提供者和卫生部门在内的各种利益相关者进行合作。 系统管理员在设计，实施和分析，并将采用人种学方法 评估研究团队的活动。我们独特的患者群体和整合的健康信息 系统将使我们能够研究外显子组测序对下游卫生保健利用的相关性 和成本。这个项目的结果，它利用了一个既定的临床遗传学范式，将提供 一个模型，以解决公平的挑战，获得外显子组测序之间的服务不足， 这些患者将来可以应用于基因组医学的其他方面。

PROJECT SUMMARY/ABSTRACT: More research is needed identify approaches to improve how patients and providers understand, communicate, and make choices about using exome sequencing to guide health care decisions. These challenges are further compounded in populations with limited literacy or other barriers to meaningfully understand or act upon results. To address these issues, this project will recruit >60% racially, ethnically, and socioeconomically diverse patients. The proposed project is an extension of our CSER1 project on carrier testing as both projects involve screening healthy people in integrated health systems to allow the unique opportunity to evaluate downstream health care decisions. Leveraging stakeholder input garnered through CSER1, the project objective is to implement a hereditary cancer risk assessment program in healthy 18-50 year-olds in primary care settings within vertically integrated health delivery systems (Kaiser Permanente) and a federal qualified health center (Denver Health) and compare the impact of exome sequencing in 1100 patients to patients who seek usual care. The project will focus on hereditary breast and ovarian cancer and Lynch syndrome, for which there are established clinical recommendations for cancer prevention. We will assess: 1) exome sequencing implementation and interpretation; 2) tailored interactions including a contextualized consent process, a novel decision aid for selecting the optional categories of additional results, and a modified approach to results disclosure and genetic counseling; 3) tools for medical interpreters (interactive web-based education) and primary care providers (electronic heath management tool); 4) the clinical utility (healthcare utilization and adherence to recommended care) and personal utility of primary and additional results from exome sequencing; 5) the costs of the program; and 6) the ethical and policy implications of considering personal utility of genomic information on decisions for health care coverage. This experienced team was highly productive in CSER1 and has the capability to successfully carry out the proposed research, with expertise in genetic epidemiology, medical genetics, health communications, health informatics, economics, anthropology, biostatistics, and bioethics. We will engage diverse stakeholders including patients, providers, and health systems administrators in the design, implementation, and analyses and will employ ethnographic methods to assess the research team activities. Our unique patient populations and integrated health information systems will allow us to investigate relevance of exome sequencing on downstream health care utilization and costs. The results of this project, which leverages an established clinical genetics paradigm, will provide a model to address challenges in equity for access to exome sequencing among underserved and diverse patients that can be applied to additional aspects of genomic medicine in the future.