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

产前基因治疗的出现：研究临床、科学和社会价值的“嵌入式伦理学”民族志

• 批准号: 10428702
• 负责人: Julia E.H. Brown
• 金额: $ 15.39万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-08 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10428702
• 关键词: Affect; Animal Model; Area; Attention; Award; Bioethics; California; Child; Clinic; Clinical; Clinical Research; Collaborations; Communities; Complement; Complex; Data; Decision Making; Diagnosis; Diagnostic; Disease; Education; Ensure; Environment; Enzymes; Ethical Analysis; Ethics; Ethnography; Exercise; Feedback; Fetus; Foundations; Future; Gene therapy trial; Gene-Modified; Genes; Genetic; Genetic Diseases; Genome; Genomic medicine; Genomics; Goals; Health; Healthcare; Human Genetics; Infrastructure; Intervention; Interview; Knowledge; Maternal Mortality; Medical Genetics; Mentors; Mentorship; Methodology; Methods; Molecular; Morbidity - disease rate; National Human Genome Research Institute; Outcome; Parents; Pathway interactions; Patient Preferences; Patients; Phase I Clinical Trials; Politics; Pregnancy; Preventive; Preventive treatment; Process; Public Participation; Reproductive Health; Reproductive Technology; Research; Research Training; Sampling; San Francisco; Scholarship; Science; Scientific Advances and Accomplishments; Shapes; Site; Social Values; Social support; Strategic vision; Structure; Technology; Therapeutic; Thinking; Time; Training; Uncertainty; Universities; career; clinical decision-making; community consultation; community engagement; cost; design; education research; ethical legal social implication; experience; fetal; frontier; gene therapy; genetic counselor; genome editing; health care availability; health disparity; health equity; health inequalities; human genomics; improved; in utero; innovation; innovative technologies; knowledge translation; maternal morbidity; maternal risk; member; postnatal; pre-clinical; precision medicine; prenatal; prenatal therapy; programs; prospective; repaired; skills; social; social disparities; social inclusion; socioeconomics; stem cells; therapy development

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.

项目概要/摘要 基因组医学和美国医疗保健已经达到了一个拐点，下一波创新浪潮即将到来 技术可能会减轻或加剧现有的健康不平等，存在多种道德、法律和社会问题。 遗传病从精准诊断过渡到预防性治疗的意义（ELSI） 重大科学不确定性和医疗保健获取不公平的社会背景。 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——将深刻影响 NHGRI 2030 战略愿景是否改善社区利益相关者的参与和公平 拟议的 K99/R00 奖为实现基因组医学提供了一个重要的机会。 通过研究三种不同的方法，将 ELSI 知识融入胎儿基因治疗的开创性过程中 对紧急胎儿基因治疗的伦理关注程度：临床、监管和社会。 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 在预防性基因治疗的关键时刻采用人种学和“嵌入式伦理”方法进行胎儿基因治疗 这项关于胎儿基因治疗的 ELSI 的多中心研究将连接精准医学和 ELSI。 诊所及其监管基础设施中发生的事情以及需要更大范围的社会价值 纳入拟议的五年培训和研究计划，以实现更大的社会包容性。 为预防性基因组医学领域的独立 ELSI 奖学金候选人做好准备， 利用民族志技能来补充 K99 获得的人类遗传学和基因组学教育， 确定了社会包容的三个障碍：1）紧张局势。 临床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； 3) 利益相关者的公平参与 这些问题体现了本提案的三个具体目标：1) 描述了为胎儿基因治疗及其“效用”做出决定的过程，根据 以及直接参与 CMFPM 最有前途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，并探讨社会价值观如何塑造不确定性 3) 考虑不同的、非患者群体的观点和程度 胎儿基因治疗的发展是否具有社会包容性（R00）。 实现这些目标将促进科学、监管、临床理解、患者和社会的理解 推动胎儿基因治疗创新的价值观。通过独特的人种学途径了解胎儿的临床前沿。 基因疗法，它将让人们了解社会包容在治疗过程中的重要性 知识转化、决策和价值创造。