Surfacing values in the economic evaluation of genomic sequencing for diagnosis of children with rare diseases

基因组测序（GS）在罕见疾病诊断方面的突破是一些 是当今医学界最令人兴奋的。罕见疾病影响着美国近3000万人， 其中三分之二是儿童。研究表明GS（包括外显子组和全基因组） 测序）可能能够为高达50%的先前未诊断的患者提供诊断， 广泛的临床和基因检测。然而，这些测试对患者的下游效益和成本， 家庭和医疗保健系统仍然定义不清，在方法上难以评估。在 为了应对这些挑战，卫生经济学和政策领域的领导人呼吁开发新的， 界定和衡量一般事务价值的跨学科方法。为了确保这些方法不 不仅准确，而且道德，关键是要考虑到价值观和偏好 各种利益相关者（即，患者、家属、临床医生、付款人）参与使用GS诊断 罕见疾病，其价值通过不同的方法学方法来定义和衡量 GS的价值。 拟议研究的目标是研究我们如何能够，以及我们应该如何定义和 测量GS对于患有罕见疾病的儿科患者的价值。这项建议有三个具体目标。目的 1：确定GS对接受GS的儿科患者的潜在下游影响范围， 罕见疾病及其家族的诊断，使用深入的民族志方法，以捕捉的观点， 不同的利益相关者。目标二：在目标1的基础上制定一个框架， GS的好处，因为它们涉及a）不同的利益相关者对GS诊断罕见疾病的价值的看法 疾病;和B）儿童罕见病患者的健康相关生活质量（HRQL）的相关领域 疾病目标三：在目标2的基础上，制定一项基于偏好的措施，用于评估 关于HRQL的GS，专门用于患有罕见遗传病的儿科患者，用于未来的经济 对GS的评价。如果成功，拟议的研究将为指导政策提供必要和及时的数据 在临床护理中有效，道德和公平地实施GS的建议。 哈雷博士将通过利用她目前在民族志和卫生服务方面的技能来实现这些目标 研究，以及在生物医学伦理学、遗传和基因组检测以及健康方面的额外培训 经济学，将在斯坦福大学生物医学伦理中心进行。哈雷博士已经是 他是一位有着高质量研究记录的有成就的学者。拟议的培训和指导 研究将为她提供更多的知识和技能，成为一个独立的， 一个跨学科的研究人员检查新的基因组技术的ELSI，重点是交叉点 医学人类学、生物医学伦理学和健康经济学的基础。

The breakthroughs in diagnosis of rare diseases made possible by genome sequencing (GS) are some of the most exciting in medicine today. Rare diseases affect nearly 30 million individuals in the United States, and two-thirds of those affected are children. Studies suggest that GS (including exome and whole genome sequencing) may be able to provide a diagnosis to up to 50 percent of patients previously undiagnosed after extensive clinical and genetic testing. However, the downstream benefits and costs of these tests for patients, families, and the healthcare system remain poorly defined and methodologically challenging to assess. In response to these challenges, leaders in health economics and policy have called for the development of new, interdisciplinary methods for defining and measuring the value of GS. In order to ensure these methods are not only accurate, but also ethical, it is critical to bring to the surface a consideration of the values and preferences of various stakeholders (i.e., patients, families, clinicians, payers) involved in the use of GS for diagnosis of rare diseases, and whose values are served by different methodological approaches to defining and measuring the value of GS. The goal of the proposed research is to examine both how we can, and how we should, define and measure the value of GS for pediatric patients with rare diseases. This proposal has three specific aims. Aim 1: to identify the range of potential downstream impacts of GS for pediatric patients undergoing GS for diagnosis of rare diseases and their families, using in-depth ethnographic methods to capture perspectives of diverse stakeholders. Aim Two: To build on Aim 1 to develop a framework mapping the range of costs and benefits of GS as they relate to a) diverse stakeholder perspectives on the value of GS for diagnosis of rare diseases; and b) relevant domains of health-related quality of life (HRQL) for pediatric patients with rare diseases. Aim Three: To build on Aim 2 to develop a preference-based measure for assessing the impact of GS on HRQL specifically for pediatric patients with rare genetic diseases for use in future economic evaluations of GS. If successful, the proposed research will provide essential and timely data to guide policy recommendations for effective, ethical, and equitable implementation of GS in clinical care. Dr. Halley will achieve these aims by drawing on her current skills in ethnography and health services research, as well as on additional training in biomedical ethics, genetic and genomic testing, and health economics, to be carried out at the Stanford Center for Biomedical Ethics. Dr. Halley is already an accomplished scholar with a track record of high-quality research. The proposed training and mentored research will provide her with the additional knowledge and skills necessary to become an independent, interdisciplinary researcher examining the ELSI of new genomic technologies, with a focus on the intersection of medical anthropology, biomedical ethics, and health economics.