Cost-effectiveness of Whole Genome Sequencing of Healthy Adults

摘要 全基因组测序具有巨大的潜力，可以通过识别出 疾病的易感性，通过告知治疗情况，促进有针对性的预防和筛查工作 当疾病确实发展时的选择，以及更多。通过假阳性，它也可能弊大于利。 研究结果，通过不必要的监测，因为不完全的遗传外显，并且因为 通过基因组测序确定的疾病可能缺乏有效的预防选择。更让人不安的是 基因组测序令人担忧的是，在健康成年人中使用基因组测序将导致医疗支出 激增不仅是由于测序、变异分类和定期重新分析的成本，而且是通过 启动一系列后续诊断测试和潜在不必要的筛查。不确定的是 将基因组测序整合到临床环境中的效用和成本正在阻碍 基因组检测政策，并阻止付款人为这些服务报销，特别是为检测 没有疾病症状的人群。对于接受基因组测试的保留意见可能是 理所当然，但目前是基于对测序的好处、危害和成本的猜测，而不是 而不是证据。为了让基因组学领域在现在和未来实现其潜力，研究计划需要 开始系统地、严格地评估这些结果。这项职业发展补助金针对的是 缺乏基因组学方面的成本效益研究人员，通过提出一个研究和培训议程来建立 关于一位年轻的临床基因组学结果研究人员的公认技能，以帮助他启动 独立职业，研究基因组测序的成本效益。候选人已经是一名 备受瞩目的研究员，曾获得NIH资助的国家研究服务奖，并拥有 出版了二十多本关于心理和行为反应的同行评议出版物 基因组信息。通过这笔拨款，这位新任命的讲师将获得额外的成本技能- 通过对医疗成本和临床试验进行为期五年的跟踪，进行有效性研究和临床试验 他的导师提出的开创性的全基因组测序随机试验的健康结果 健康成年人的临床护理，MedSeq项目。应聘者还将获得决策建模和 通过创建预测基因组的成本和效用的决策分析模型来处理大数据 对病人的一生进行测序。最后，应聘者将确定将提供 通过对基因组进行信息价值分析来实现成本效益研究的最大价值 在健康的成年人中进行测序。拟议中的研究结果不仅将产生急需的 深入了解基因组测序在健康成年人中的价值，但也将为候选人提供 R01提交的基本技能和试点数据，以了解基因组的成本效益 在病人的生活中进行测序。

ABSTRACT Whole genome sequencing has vast potential to improve the care of generally healthy adults by identifying predispositions for disease to facilitate targeted prevention and screening efforts, by informing treatment options when illnesses do develop, and more. It may also cause more harm than good through false-positive findings, through unnecessary monitoring because of incomplete genetic penetrance, and because the conditions identified by genomic sequencing may lack effective prevention options. Adding to the unease about genomic sequencing are concerns that its use among healthy adults will cause healthcare expenditures to surge not only due to the costs of sequencing, variant classification, and periodic re-analysis, but also by initiating a cascade of follow-up diagnostic testing and potentially-unnecessary screening. Uncertainties about the utility and costs of integrating genomic sequencing into clinical settings are hindering the development of genomic testing policies and discouraging payers from reimbursing for these services, particularly for testing of populations that are asymptomatic for disease. Reservations about embracing genomic testing may be warranted, but are currently based in speculation about the benefits, harms and costs of sequencing rather than evidence. For the field of genomics to achieve its potential now and in the future, research programs need to begin systematically assessing these outcomes with rigor. This career development grant addresses the dearth of cost-effectiveness researchers in genomics by proposing a research and training agenda that builds on the recognized skills of a young outcomes researcher in clinical genomics to help him launch an independent career investigating the cost-effectiveness of genomic sequencing. Already, the candidate is a high-profile researcher, having received an NIH-funded National Research Service Award and having published over two dozen peer-reviewed publications about psychological and behavioral responses to genomic information. Through this grant, this newly-appointed Instructor will gain additional skills in cost- effectiveness research alongside clinical trials by conducting a five-year follow-up of the healthcare costs and health outcomes from his proposed mentor's pioneering randomized trial of whole genome sequencing in the clinical care of healthy adults, the MedSeq Project. The candidate will also gain skills in decision modeling and working with “big data” by creating a decision-analytic model that projects the costs and utility of genomic sequencing over patients' lifetimes. Lastly, the candidate will identify the areas of research that will provide the most value for cost-effectiveness research by conducting a value-of-information analysis about genomic sequencing among healthy adults. Findings from the proposed research will not only generate critically-needed insight about the value of genomic sequencing among healthy adults, but will also provide the candidate with foundational skills and pilot data for an R01 submission to understand the cost-effectiveness of genomic sequencing throughout patients' lives.