Experiences and Outcomes in Early Adopters of Predispositional Sequencing

项目摘要/摘要 基因组测序(GS)的潜力预示着精确医学的新时代 来自健康个体的序列信息可以预测和预防疾病。目前，这两个好处 而在没有适应症的情况下进行基因组测序的危害在很大程度上是假设的。在这不确定的情况下 环境，几千个人已经有了前置性的个人基因组测序 (PPG)，通过学术研究项目或商业服务，预计还会有数千人 要尽快做到这一点。这些人中的大多数显然是健康的，否则就不会得到GS 由于缺乏医疗需要，但对非诊断性疾病的测序越来越感兴趣和活跃 目的加强疾病预防和健康管理。早期采用者构成了一个独特的队列 在这样的测试普及之前，值得研究的个人。我们收集了一些 这些项目组成了一个研究联盟，并试行了一项基于网络的调查，以更好地了解医学、 在没有指征的情况下对成人进行排序的行为和经济影响。到目前为止，有近1400人 已被邀请参加我们的个人基因组测序结果(PeopleSeq)联盟，与 在这项初步研究中，约有50%的人联系了他们。总共有658个人 在PPGS结果公布后完成了这项初步调查，我们的目标是增加一个额外的 2400名参与者与新的测序小组合作。 在这个提案中，我们提出了一个建立在项目基础上的计划和方法。我们会 扩大志愿参加排序的机会，将代表人数不足的潜在参与者包括在内 通过提供教育项目，包括在几个历史上属于黑人的机构进行排序，来保护少数族裔。 随着时间的推移，我们将进行基于网络的调查，并采用混合方法，包括 对选定的个人进行定性访谈。作为第一个纵向队列研究，大多数情况下 对于接受PPGS的健康成年人，我们将广泛评估PPGS的拟议风险和好处， 包括对医疗保健利用的短期和长期影响、心理影响和与健康相关的 结果。我们将确定获得了哪些类型的后续临床护理(以及如何覆盖 经济上)，并评估它是否在医疗上有益。我们的研究结果将为准备工作提供参考 随着越来越多的人寻找DNA测序并对其做出反应，医疗保健系统也变得越来越重要。此外，我们还将收取 关于同意的参与者的实际基因组报告，并将表征临床上 重大发现。我们将把这些基因组信息与有关后续行动的调查数据结合起来 探索PPGS的潜力，以提供有助于预防和健康的临床有用信息 管理层。

PROJECT SUMMARY/ABSTRACT The potential of genomic sequencing (GS) promises a new era of precision medicine in which sequence information from healthy individuals can anticipate and prevent disease. At present, both the benefits and harms of genomic sequencing conducted without indication are largely hypothetical. In this uncertain environment, several thousand individuals have already had predispositional personal genome sequencing (PPGS) through academic research projects or commercial services, and many thousands more are projected to do so soon. The majority of these individuals are apparently healthy and would otherwise not receive GS due to lack of medical necessity, but there is growing interest and activity in sequencing for non-diagnostic purposes to enhance disease prevention and health management. Early adopters constitute a unique cohort of individuals that are worthy of study before such testing becomes widespread. We have gathered a number of these projects into a research consortium and piloted a web-based survey to better understand the medical, behavioral and economic impacts of sequencing adults without indication. To date, nearly 1,400 individuals have been invited to participate in our Personal Genome Sequencing Outcomes (PeopleSeq) Consortium, with approximately 50% of individuals contacted enrolling in this preliminary study. A total of 658 individuals have completed this preliminary survey after having their PPGS results disclosed, and we aim to add an additional 2,400 participants by partnering with new sequencing groups. In this proposal, we present a plan and methodology to build upon our project’s foundation. We will expand the opportunity to volunteer for sequencing to include potential participants from underrepresented minorities by offering educational programs that include sequencing at several Historically Black institutions. We will conduct web-based surveys over time and incorporate a mixed-methods approach by including qualitative interviews among selected individuals. As the first longitudinal cohort study of mostly generally healthy adults who receive PPGS, we will extensively evaluate the proposed risks and benefits of PPGS, including short- and long-term impacts on healthcare utilization, psychological impact, and health-related outcomes. We will determine what kinds of follow-up clinical care were obtained (and how it was covered financially), and assess whether it was medically beneficial. Findings from our study will inform preparations in the healthcare system as more individuals seek out and react to DNA sequencing. In addition, we will collect actual genomic reports on consenting participants and will characterize the number and nature of clinically significant findings. We will combine this genomic information with survey data about follow-up actions to explore the potential of PPGS to provide clinically useful information that can assist in prevention and health management.