Health care system-led familial risk notification: design and ethical assessment

项目总结/摘要 背景基因检测具有多代影响，因为可采取行动的致病变异可以 确定多个家庭成员处于危险之中。目前在美国，一个人在可诉的风险，通过 基因检测负责联系他们自己的家庭成员和沟通风险。然而，在这方面， 不完全或不向亲属披露的情况很普遍，多达三分之一的有风险的亲属可能 可采取行动的遗传学发现没有通知。尽管初步数据表明，基因检测患者 愿意让他们的卫生系统直接联系在同一系统接受护理的亲属， 他们的潜在风险，这种推广将如何在实践中工作还没有得到很好的理解， 临界间隙 方法.我们将进行以人为本的设计和可行性研究的卫生系统为主导的家庭 外联和风险通知。所有项目活动都将遵循学习医疗保健的道德框架 系统，临床护理和公共卫生，以及新兴的奖学金的关系概念化， 在遗传服务中，医生的自主权和对病人和家庭的信托义务。 第一个目标将使用定性的以人为本的设计方法，以确定病人的需求， 亲属以及临床和卫生系统利益攸关方。我们将举办两轮设计工作坊， 未来的研讨会和名义组技术与先证者及其亲属;并最终确定设计， 临床医生和组织利益相关者。这一目标的产物将是一套可推广的要求， 我们和其他直接联系亲属的卫生系统使用。 在第二个目标中，我们将在有限的亲属样本中测试外展过程。我们将 实施目标1中设计的工作流程，其中有一组预期的卫生系统成员， BRCA 1/2或Lynch综合征的检测结果。我们将确定每个同意的先证者的 属于同一卫生系统的遗传亲属。亲属将被随机分配 目标1中设计的外联进程，或不再开展外联活动。我们将以先证者为单位 随机化，以允许家庭内的聚类，并分层随机化BRCA或林奇测试。 结果评估。采用深度认知访谈和问卷调查相结合的方法， 评估的结果将包括过程的可接受性、对护理和治疗/检测的满意度 决定、直接外联对家庭沟通的影响、通知后采取的行动，以及 意想不到的后果。我们将评估直接推广在增加基因治疗使用方面的有限功效。 在6-8周时，接受直接外展的亲属与未接受直接外展的亲属进行咨询和测试。

PROJECT SUMMARY/ABSTRACT BACKGROUND. Genetic testing has a multigenerational impact, as actionable pathogenic variants can identify multiple family members at risk. Currently in the United States, a person at actionable risk through genetic testing is responsible for contacting their own family members and communicating risk. However, incomplete or non-disclosure to relatives is prevalent, and up to a third of at-risk relatives who may have actionable genetic findings go un-notified. Despite preliminary data suggesting that genetic testing patients are open to having their health system directly contact relatives who receive care in the same system to notify them of their potential risk, how such outreach would work in practice is not well understood and represents a critical gap. METHODS. We will conduct a human-centered design and feasibility study of health system-led familial outreach and risk notification. All project activities will be guided by ethical frameworks of learning healthcare systems, clinical care, and public health, as well as by emerging scholarship on relational conceptualizations of autonomy and clinicians' fiduciary obligations to patients and families in genetic services. The first aim will use qualitative human centered design methods to ascertain the needs of patients, their relatives, and clinical and health system stakeholders. We will conduct two rounds of design workshops using future workshop and nominal group techniques with probands and their relatives; and finalize the design with clinician and organizational stakeholders. The product of this aim will be a set of generalizable requirements for use by ours and other health systems engaged in direct outreach to relatives. In the second aim, we will test the outreach process in a limited prospective sample of relatives. We will implement the workflow designed in Aim 1 with a prospective cohort of health system members receiving actionable results from testing for BRCA1/2 or Lynch syndrome. We will identify each consenting proband's genetic relatives who are members of the same health system. Consenting relatives will be randomly assigned to either the outreach process designed in Aim 1, or to no further outreach. We will use the proband as the unit of randomization to allow for clustering within family, and stratify randomization on BRCA or Lynch testing. OUTCOME ASSESSMENT. Using a combination of in-depth cognitive interviews and survey, feasibility outcomes assessed will include acceptability of the process, satisfaction with care and with treatment/testing decisions, impact of direct outreach on family communications, actions taken after notification, and any unintended consequences. We will assess limited efficacy of direct outreach in increasing use of genetic counseling and testing in relatives who received direct outreach compared to those who did not at 6-8 weeks.