Risk-Benefit Trade-Offs for Whole Genome Sequencing

描述（由申请人提供）：新技术使人们期待已久的负担得起的基因组的到来，能够快速和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目前正在临床护理中提供，预计在不久的将来会得到更广泛的应用，特别是在癌症中。然而，这种技术进步可能会超过我们在临床实践中有效使用它和解决相关卫生政策问题的能力。我们的目标是通过使用系统和定量方法，从患者、提供者、医疗保健提供系统和社会的角度评价WGS的潜在获益-风险权衡。我们的研究目标是：1）分析患者和医生如何使用信息价值的决策理论模型评估WGS的获益-风险权衡; 2）在医疗保健系统和社会层面经验性评估WGS的获益-风险权衡。对于目标1，我们将使用一般人群样本（MedSeq项目）测量和比较WGS首次随机临床试验参与者中患者和医生对WGS的偏好，该试验由哈佛医学院和全国代表性样本领导，使用定量，统计学上严格的方法（联合分析）。目标2将通过两个次级目标来实现。在目标2a中，我们将对WGS的医疗保健决策中如何考虑获益-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;和（2）使用目标1和2a，MedSeq和我们以前的分析数据，从WGS识别Lynch综合征中可能发现的一个原型成本效益模型。这将是第一个全国性的研究，我们的知识，病人和医生的偏好相关的WGS在一般人群中，比较偏好从临床试验到全国人口，并系统地检查WGS的影响，为医疗保健系统和社会。拟议的工作是重要的，因为它将产生如何最有效和最有效地采用WGS的证据，同时也了解其局限性，这些信息将有助于 患者、供应商、研究人员和政策制定者。我们的工作将对临床实践和卫生政策产生广泛的影响和影响，并将建立在目前正在进行的研究基础上。 由我们经验丰富的多元化团队进行。总之，这项研究将解决一个重要的课题，采用创新的适应方法。这项研究是在WGS发展的正确时间提出的，当时研究结果将对新兴科学产生影响，当我们可以利用正在进行的试验的资源时，当我们有合适的团队进行研究时。

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.