Risk-Benefit Trade-Offs for Whole Genome Sequencing

描述（由申请人提供）：新技术使期待已久的可负担基因组的到来-能够快速廉价地对个体或肿瘤的整个基因组进行测序[全基因组测序（WGS）]。WGS现已用于临床护理，并有望在不久的将来得到更广泛的应用，特别是在癌症方面。然而，这种技术进步有可能超过我们在临床实践中有效利用它并解决相关卫生政策问题的能力。我们的目的是通过系统和定量的方法，从患者、提供者、卫生保健提供系统和社会的角度评估WGS的潜在利益-风险权衡。我们的研究目的是：1)利用信息价值的决策理论模型分析患者和医生如何评估WGS的利益-风险权衡；2)在卫生保健系统和社会层面对WGS的利益-风险权衡进行实证评估。在目的1中，我们将测量和比较患者和医生对WGS的偏好，这是第一项使用一般人群样本（MedSeq项目）的WGS随机临床试验的参与者，该试验由哈佛医学院领导，并使用定量的、统计严谨的方法（联合分析）和具有全国代表性的样本。目标2将通过两个子目标来实现。在目标2a中，我们将对在WGS的医疗保健决策中如何考虑利益-风险权衡进行政策分析，包括覆盖/报销决策和临床指南制定，以及它们如何与更成熟的基因检测进行比较。在目标2b中，我们将开发(1)一个框架来概念化、识别和定义评估WGS价值所需的数据；(2)使用Aims 1和2a、MedSeq和我们之前的分析的数据，对WGS的一个可能发现——Lynch综合征的鉴定——建立一个原型成本效益模型。这将是我们了解普通人群中与WGS相关的患者和医生偏好的第一个全国性研究，比较临床试验与全国人群的偏好，并系统地检查WGS对卫生保健系统和社会的影响。拟议的工作意义重大，因为它将提供关于如何最有效和高效地采用WGS的证据，同时也了解其局限性-将对以下方面有用的信息

DESCRIPTION (provided by applicant): New technologies are enabling the arrival of the much awaited affordable genome the ability to sequence an individuals or a tumors entire genome quickly and inexpensively [whole genome sequencing (WGS)]. WGS is now being offered in clinical care and is expected to become more widely used in the near future, particularly in cancer. However, this technological advance threatens to outpace our ability to use it effectively in clinical practice and to address the associated health policy issues. Our objective is to evaluate the potential benefit- risk tradeoffs of WGS from the perspectives of patients, providers, the health care delivery system, and society by using systematic and quantitative approaches. Our study aims are: 1) to analyze how patients and physicians evaluate WGS benefit-risk tradeoffs using a decision-theoretic model of the value of information and 2) to empirically assess benefit-risk tradeoffs of WGS at the health care system and societal levels. For Aim 1 we will measure and compare patient and physician preferences for WGS in participants of the first randomized clinical trial of WGS using a general population sample (MedSeq Project), which is being led by Harvard Medical School and a nationally representative sample using quantitative, statistically rigorous methods (conjoint analysis). Aim 2 will be accomplished using two sub-aims. In Aim 2a we will conduct a policy analysis of how benefit-risk tradeoffs are considered in health care decision making for WGS, including coverage/reimbursement decisions and clinical guideline development, and how they compare to those of more established genetic tests. In Aim 2b we will develop (1) a framework to conceptualize, identify, and define data needed to assess the value of WGS; and (2) a prototypical cost-effectiveness model of one likely finding from WGS�identification of Lynch syndrome�using data from Aims 1 and 2a, MedSeq, and our previous analyses. This will be the first national study to our knowledge of patient and physician preferences relevant to WGS in the general population, to compare preferences from a clinical trial to a national population, and to systematically examine implications of WGS for the health care system and society. The proposed work is significant in that it will produce evidence of how WGS can be most effectively and efficiently adopted while also understanding its limitations�information that will be useful to patients, providers, researchers, and policymakers. Our work will have broad impact on and implications for clinical practice and health policy and will build on the research currently being conducted by our experienced and diverse team. In sum, this study will address a significant topic using innovative adaptation of methods. The study is being proposed at the right time in the development of WGS�a time when the study results will have an impact on the emerging science, when we can leverage the resources of an ongoing trial, and when we have the right team in place to conduct the research.