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; 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.

项目摘要/摘要 基因组医学和美国医疗保健已经达到了影响点，下一波创新浪潮 技术可能会减轻或加剧现有的健康不平等。有多种道德，法律和社会 从精度诊断到预防治疗遗传疾病的含义（ELSI） 严重科学不确定性和不平等医疗保健获得的社会背景。实施和 ELSI对胎儿基因疗法的监督 - 直到现在，一种假设的练习将深刻塑造 NHGRI 2030的战略愿景是否改善了社区利益相关者的参与和公平 可以实现基因组医学。拟议的K99/R00奖给 通过研究三个不同的不同 新兴胎儿基因疗法的道德关注程度：临床，监管和社会。通过 跨学科培训，指导和与加利福尼亚大学旧金山中心合作 用于母亲 - 宠物精密医学（CMFPM），斯坦福大学生物医学伦理中心（SCBE）和 UCSF史丹福德的监管科学与创新卓越中心（CERSI），该项目追求 在预防性关键时刻，民族志和“嵌入式伦理”方法用于胎儿基因治疗 精密医学和ELSI研究。这项关于胎儿基因疗法ELSI的多人研究将连接 在诊所及其监管基础设施中发生的事情，具有较大规模的社会价值 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科学做好准备， 利用人种学技能来完成K99在人类遗传学和基因组学领域获得的教育， 生物伦理学和社区参与方法。确定了三个社会包容性的障碍：1）紧张局势 在临床和社会效用之间； 2）缺乏有关不确定性决策过程的经验数据； 3）公平的利益相关者参与。这些问题为此提案提供了三个具体目的：1） 根据临床医生的说法，描述有关胎儿基因疗法及其“效用”的决定的过程。 以及直接参与CMFPM最有前途的胎儿基因和分子疗法的患者 （K99）; 2）记录诊所中如何管理不确定性并探索如何根据社会价值来塑造这一点 和社会经济支持（K99）； 3）说明潜水员，非患者社区的观点和程度 胎儿基因疗法的发展是或不是社会包容性的（R00）。教育和研究 实现这些目标将提高人们对科学，监管，临床，患者和社会的理解 驱动胎儿基因治疗创新的值。独特的人种学进入胎儿临床前沿 基因疗法，它将提供对社会包容的重要性的理解 知识翻译，决策和价值制定。