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 疾病的易感性，以促进有针对性的预防和筛查工作， 疾病发生时的选择等等。它也可能通过假阳性造成弊大于利 研究结果，通过不必要的监测，因为不完整的遗传学，因为 通过基因组测序鉴定的病症可能缺乏有效的预防选择。更令人不安的是， 基因组测序担心它在健康成年人中的使用将导致医疗保健支出， 激增不仅是由于测序、变异分类和定期重新分析的成本， 启动一系列后续诊断测试和可能不必要的筛查。不确定性 将基因组测序整合到临床环境中的效用和成本阻碍了 基因组检测政策，并阻止支付者偿还这些服务，特别是对检测 没有疾病症状的人群。对接受基因组检测的保留意见可能是 有理由，但目前基于对测序的好处，危害和成本的猜测， 比证据。为了使基因组学领域在现在和将来发挥其潜力，研究计划需要 开始系统地评估这些结果。这项职业发展补助金涉及 缺乏成本效益的研究人员在基因组学，提出了研究和培训议程，建立 一个年轻的临床基因组学成果研究人员的公认技能，以帮助他推出一个 研究基因组测序的成本效益的独立职业。候选人已经是一个 高知名度的研究人员，获得了NIH资助的国家研究服务奖， 发表了二十多篇同行评议的出版物， 基因组信息通过这笔赠款，这位新任命的导师将获得额外的技能，在成本- 通过对医疗费用进行为期五年的随访，在临床试验的同时进行有效性研究， 健康结果从他的建议导师的开创性随机试验的全基因组测序在 健康成人的临床护理，MedSeq项目。候选人还将获得决策建模技能， 通过创建一个决策分析模型来处理"大数据"，该模型预测基因组的成本和效用， 对病人的生命周期进行排序最后，候选人将确定研究领域，将提供 最有价值的成本效益研究，通过进行基因组信息价值分析， 在健康成年人中进行测序。拟议研究的结果不仅将产生急需的 对健康成年人基因组测序价值的洞察力，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 在病人的一生中进行排序。

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.