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有以下几点 是当今医学界最令人兴奋的事情之一。罕见疾病影响着美国近3000万人， 受影响的人中有三分之二是儿童。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%的以前未被诊断的患者提供诊断 广泛的临床和基因测试。然而，这些检测对患者的下游好处和成本， 家庭和医疗保健系统的定义仍然不明确，在评估方法上具有挑战性。在……里面 为了应对这些挑战，卫生经济和政策领域的领导人呼吁开发新的、 定义和衡量GS价值的跨学科方法。为了确保这些方法不会 不仅是准确的，而且是合乎道德的，关键是将对价值观和偏好的考虑公之于众 不同的利益相关者(即，患者、家庭、临床医生、付款人)参与使用GS诊断 罕见疾病，其价值由不同的定义和衡量方法所服务 GS的价值。 拟议研究的目标是研究我们如何以及应该如何定义和 测量儿科罕见病患者的GS值。这项提议有三个具体目标。目标 1：确定GS对接受GS治疗的儿童患者的潜在下游影响范围 罕见疾病及其家庭的诊断，使用深入的人种学方法，以捕捉 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，绘制费用和 GS的好处，因为它们涉及到)不同的利益相关者对GS诊断罕见疾病的价值的看法 疾病；以及b)罕见疾病儿童患者的健康相关生活质量(HRQL)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，以评估#年的影响 专为患有罕见遗传病的儿科患者制定的HRQL在未来经济中的应用 对GS的评价。如果成功，拟议的研究将提供必要和及时的数据来指导政策 在临床护理中有效、合乎道德和公平地实施GS的建议。 哈雷博士将利用她目前在人种学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、基因和基因组测试以及健康方面的额外培训 经济学，将在斯坦福生物医学伦理中心进行。哈雷博士已经是一名 具有高质量研究记录的有成就的学者。建议的培训和指导 研究将为她提供必要的额外知识和技能，使她成为一个独立、 跨学科研究人员研究新基因组技术的ELSI，重点放在交集上 医学人类学、生物医学伦理学和卫生经济学。

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.