Aligning policy and healthcare services with Veterans' values and preferences for results from Whole Genome Sequencing

在过去的十年中，基因组医学已经从单基因检测迅速扩展到包括下一代- 代测序（NGS）测试，如全基因组测序（WGS），揭示了广泛的 基因组信息在同一时期，基因组测序的技术成本已经从 从2003年的3000多万美元增加到2016年的约1,000美元。VA和国家正在做出重大的 对研究基础设施的投资，以加速新基因组技术的转化， 支持个性化的医疗保健，其中风险评估，诊断，预后和治疗由 一个人的基因组VA基因组医学计划的百万退伍军人计划（MVP）于2009年启动 2015年启动的2.15亿美元的国家精准医学计划预计将进一步加快 个性化医疗保健中的基因组发现和翻译。与国家精准医疗同步 VA正在制定战略，向未来50万人发布基因组分析结果 将参加MVP队列和WGS以及其他基于基因组的测试的退伍军人开始被 在研究之外使用，以告知VA临床环境中的疾病风险、诊断和治疗。 与政府和公众对NGS应用程序潜力的热情并列， WGS在基因组信息的数量方面所能提供的信息之间存在巨大差距， 什么样的结果可以被解释为患者会发现有意义。挑战之一是 WGS信息，包括与测试的原始目的无关的发现以及 在预防、诊断和治疗疾病方面的意义不确定。随着WGS和其他 基于基因组的测试在VA，有一个迫切需要了解什么信息退伍军人认为将是 在他们的医疗保健中很重要。然而，很少有系统的定量信息可用于VA领导 决策如何退伍军人将评估WGS信息的价值，或他们的偏好， 医疗保健服务需要解释的结果及其对健康和医疗保健的影响。 拟议的项目是及时的，解决了退伍军人偏好知识的重大差距， 在关键时刻利用机会与关键的VA利益相关者（退伍军人和VA高管）进行接触 当新技术的引入需要临床实践的适应时。在这个项目中，我们 目标是建立一个基础，了解1）退伍军人如何重视WGS和其他 NGS启用测试; 2）退伍军人更喜欢什么医疗服务，以帮助他们理解来自 这些测试，并在他们的医疗保健中使用的结果;和3）如何VA临床领导人和政策制定者使用 了解退伍军人在发展临床服务时对WGS的价值观和偏好， 结合来自WGS和其他基于基因组的测试的信息。 为了实现该项目的目标，我们使用了连续的混合方法（定性-定量-定性）。 我们将使用焦点小组和结构化认知来确定退伍军人对WGS的价值观和偏好 采访，然后进行一个全国人口为基础的调查退伍军人的喜好使用选择为基础的 联合分析为了翻译关于退伍军人偏好的调查结果，我们将进行便利的审议， 过程小组参与讨论退伍军人的观点如何可以告知VA政策， 临床基因组学 这个项目是创新的。其严格的设计和强大的利益相关者参与方法预计将 为临床基因组医学中以退伍军人为中心的护理做出贡献。此外，研究结果将与以下方面高度相关： 关于如何披露WGS和其他基于基因组的测试结果的VA执行决策， 老兵

Over the past decade, genomic medicine has rapidly expanded from single gene testing to include next- generation sequencing (NGS) tests, such as Whole Genome Sequencing (WGS), that reveal extensive genomic information. During this same time period, the technical cost of sequencing a genome has fallen from over $30 million in 2003 to approximately $1,000 in 2016. VA and the nation are making significant investments in the research infrastructure needed to accelerate the translation of new genomic technologies to support personalized healthcare where risk assessment, diagnosis, prognosis, and treatment are informed by a person's genomics. The VA Genomic Medicine Program's Million Veterans Program (MVP) initiated in 2009 and the national $215 million Precision Medicine Initiative launched in 2015 are expected to further speed genomic discoveries and translation in personalized healthcare. In step with the national Precision Medicine Initiative, the VA is developing strategies to release the results of genomic analyses to the next 500,000 Veterans who will be enrolled in the MVP cohort and WGS and other genome-based testing is beginning to be used beyond research, to inform disease risk, diagnosis, and treatment, in VA clinical settings. Juxtaposed with government and public enthusiasm for the potential of NGS enabled applications, a substantial gap exists between what WGS can deliver in terms of the quantity of genomic information, and what results can be interpreted that patients would find meaningful. One of the challenges is the complexity of WGS information that will include findings unrelated to the original purpose of testing and results that have uncertain significance in preventing, diagnosing, and treating disease. With emerging use of WGS and other genome-based testing in VA, there is an urgent need to understand what information Veterans think would be important in their healthcare. However, little systematic quantitative information is available for VA leadership decision making on how Veterans would assess the value of WGS information, or their preferences for the healthcare services needed to interpret the findings and their implications for health and healthcare. The proposed project is timely, addressing a significant gap in knowledge of Veterans' preferences and taking advantage of an opportunity to engage key VA stakeholders--Veterans and VA executives--at a critical moment when the introduction of new technologies will require the adaptation of clinical practices. In this project, our goal is to establish a foundation for understanding 1) how Veterans value the findings from WGS and other NGS enabled tests; 2) what healthcare services Veterans prefer to help them comprehend the information from these tests and to use the findings in their healthcare; and 3) how VA clinical leaders and policy makers use knowledge of Veterans' values and preferences for WGS in their development of clinical services that incorporate information from WGS and other genome-based tests. To accomplish the aims of the project, we used sequential mixed methods (qualitative-quantitative-qualitative). We will identify Veterans' values and preferences for WGS using focus groups and structured cognitive interviews and then conduct a national population-based survey of Veterans' preferences using choice-based conjoint analysis. To translate findings on Veterans' preferences, we will conduct facilitated deliberative process groups to engage VA leaders in discussion about how Veterans' perspectives can inform VA policy in clinical genomics. This project is innovative. Its rigorous design and strong stakeholder engagement methods are expected to contribute to Veteran-centered care in clinical genomic medicine. Further, the findings will be highly relevant to VA executive decision-making about how to disclose the results of WGS and other genome-based tests to Veterans.