The Emergence of Prenatal Gene Therapy: An “Embedded Ethics” Ethnography investigating Clinical, Scientific and Societal Values

项目摘要/摘要 基因组医学和美国医疗保健已经到达一个拐点，在这里，下一波创新浪潮 技术可能会缓解或加剧现有的健康不平等。有道德、法律和社会的多重因素 遗传病从精确诊断过渡到预防性治疗的意义(ELSI) 存在重大科学不确定性和不公平的医疗保健服务的社会背景。实施和实施 ELSI对胎儿基因治疗的研究监督--到目前为止还只是一个假设的练习--将深刻地塑造 NHGRI 2030战略愿景是否改善了社区利益相关者的参与度和公平性 基因组医学可以实现。拟议的K99/R00奖提供了一个重要的机会 将ELSI知识融入胎儿基因治疗的开创性过程中，通过研究三个不同的 紧急胎儿基因治疗的伦理关注度：临床、管理和社会。穿过 跨学科培训、指导以及与加州大学旧金山分校中心的合作 母婴精准医学(CMFPM)、斯坦福生物医学伦理中心(SCBE)和 加州大学旧金山分校-斯坦福大学监管科学与创新卓越中心(CERSI)，该项目致力于 预防疾病关键时刻胎儿基因治疗的人种学和“嵌入伦理学”方法 精准医学和ELSI研究。这项关于胎儿基因治疗ELSI的多点研究将与 诊所发生了什么，以及它的监管基础设施，以及需要更大规模的社会价值观 被纳入，以实现更大的社会包容性。拟议的五年培训和研究计划 为预防基因组医学领域的独立ELSI奖学金候选人做准备，由 利用人种学技能来补充K99获得的人类遗传学和基因组学教育， 生物伦理学和社区参与方法。确定了社会包容的三个障碍：1)紧张 临床效用和社会效用之间的关系；2)由于不确定性，缺乏决策过程的经验数据； 以及3)公平的利益相关者参与。这些问题决定了这项建议的三个具体目标：1) 根据临床医生的说法，描述影响胎儿基因治疗决策的过程及其“效用” 以及直接参与CMFPM最有希望的胎儿基因和分子治疗的患者 (K99)；2)记录临床中如何管理不确定性，并探索社会价值观如何塑造这种不确定性 和社会经济支持(K99)；以及3)考虑到不同的、非患者社区的观点和程度 胎儿基因治疗的发展是否具有社会包容性(R00)。教育和研究以 实现这些目标将促进对科学、法规、临床、患者和社会的理解 推动胎儿基因治疗创新的价值观。以独特的人种学方式接触到胎儿的临床前沿 基因治疗，它将提供对社会包容在过程中的重要性的理解 知识转化、决策和价值制定。

Project Summary/Abstract Genomic medicine and U.S. healthcare have reached an inflection point, where the next wave of innovative technologies may alleviate or exacerbate existing health inequity. There are multiple ethical, legal and social implications (ELSI) of transitioning from precision diagnosis to preventive treatments for genetic disease in a societal context of significant scientific uncertainty and inequitable healthcare access. The implementation and ELSI research oversight of fetal gene therapy – until now a hypothetical exercise – will profoundly shape whether the NHGRI 2030 strategic vision for improved community stakeholder engagements and equitable genomic medicine can be realized. The proposed K99/R00 Award presents a significant opportunity to incorporate ELSI knowledge into the pioneering processes of fetal gene therapy by investigating three distinct levels of ethical concern for emergent fetal gene therapy: clinical, regulatory and societal. Through interdisciplinary training, mentorship, and collaborations with the University of California, San Francisco Center for Maternal-Fetal Precision Medicine (CMFPM), the Stanford Center for Biomedical Ethics (SCBE) and the UCSF-Stanford Center of Excellence in Regulatory Science and Innovation (CERSI), this project pursues an ethnographic and “embedded ethics” approach to fetal gene therapy at a critical juncture in preventive precision medicine and ELSI research. This multi-sited study on the ELSI of fetal gene therapy will connect what happens in the clinic, and its regulatory infrastructures, with the larger-scale societal values that will need to be incorporated to achieve greater social inclusion. The proposed five-year training and research program prepares the candidate for independent ELSI scholarship in the field of preventive genomic medicine, by harnessing ethnographic skills to complement a K99 acquired education in human genetics and genomics, bioethics and community engagement methods. Three barriers to social inclusion are identified: 1) tensions between clinical and social utility; 2) a lack of empirical data on decision-making processes given uncertainty; and 3) equitable stakeholder engagements. These problems inform three specific aims of this proposal: 1) to describe the processes that inform decisions about fetal gene therapy and its ‘utility,’ according to clinicians and patients who are directly involved in the most promising fetal gene and molecular therapies at CMFPM (K99); 2) to document how uncertainty is managed in the clinic and explore how this is shaped by social values and socioeconomic supports (K99); and 3) to account for diverse, non-patient community views and the extent to which fetal gene therapy developments are or are not socially inclusive (R00). Education and research to fulfill these aims will advance understanding about the scientific, regulatory, clinical, patient, and societal values that drive fetal gene therapy innovations. With unique ethnographic access to the clinical frontier of fetal gene therapy, it will provide an understanding of the importance of social inclusion during the process of knowledge translation, decision-making, and value-making.