Informing Ethical Translation of Xenotransplantation Clinical Trials

为异种移植临床试验的伦理翻译提供信息

基本信息

批准号：
10279335
负责人：
Elisa J Gordon
金额：
$ 50.08万
依托单位：
HASTINGS CENTER, INC.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-09 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10279335
关键词：
20 year old Address Advisory Committees Affect Animal Organ Animals Bioethics Bioethics Consultants Case Study Clinical Clinical Research Clinical Trials Clinical trial protocol document Communicable Diseases Data Coordinating Center Decision Aid Decision Making Development Eligibility Determination Endogenous Retroviruses Enrollment Ensure Ethics Evaluation Family suidae Future Guidelines Health Heart Human Human Research Ethics Human Subject Research Immunosuppression Informed Consent Institution Institutional Review Boards Insurance Carriers Interview Kidney Kidney Transplantation Liver Medicine Methods Organ Organ Transplantation Outcome Pan Genus Papio Patient Participation Patients Perception Policies Psychiatrist Psychologist Public Health Recommendation Renaissance Reporting Research Research Ethics Research Personnel Risk Science Scientific Advances and Accomplishments Scientist Site Skin Solid Structure Surgeon Surveys Survival Rate Techniques Testing Time Translating Translational Research Translations Transplant Recipients Transplantation United States Universities Update Waiting Lists Xenograft procedure Zoonoses beneficiary clinical care design disease transmission disorder risk experimental study first-in-human genetic technology genome editing human subject innovation islet member nonhuman primate novel organ allocation patient oriented pre-clinical research safety testing sound success survival outcome translational scientist transmission process transplant centers

项目摘要

PROJECT SUMMARY Xenotransplantation (XTx) is a novel experimental treatment that involves transplanting organs from nonhuman animals into humans. Due to the scarcity of human organs for transplantation, XTx could help alleviate the organ shortage, which is an ongoing public health problem. Early experimental xenotransplants were performed in the U.S. from the 1960s to 1990s, involving a chimpanzee kidney, a baboon heart, and a baboon liver. Despite holding great promise, XTx experiments ended in the late 1990s due to scientific and ethical challenges. Today, XTx is undergoing a renaissance. Scientific advances in immunosuppression and genome editing techniques have mitigated the risk of zoonotic disease transmission. The transplant field is primed to conduct XTx clinical trials and then translate findings to clinical care. However, available guidelines for conducting XTx clinical trials are outdated, do not address advances in the science of XTx, do not account for stakeholders’ concerns, and do not consider the impact on policy changes to organ allocation. The overall objective of the proposed study is to identify appropriate ethical and policy guidance for translational solid organ XTx clinical trials. The research team includes national bioethics leaders at The Hastings Center, Northwestern University, and Rutgers University, with The Hastings Center serving as the data coordinating center. We will conduct in-depth interviews with transplant patients, transplant clinicians, transplant regulators, and human subjects ethics regulators, and obtain input from an Ethics and Policy Advisory Committee comprised of experts in translational science and bioethics to: (1) assess XTx stakeholders’ perceptions and concerns about ethical and policy challenges for XTx clinical trials; (2) develop XTx stakeholder decision aids that help patients, clinicians, and institutional review boards to evaluate, design, and oversee XTx clinical trials, respectively; and (3) develop recommendations for the ethical translation of XTx clinical trials. Updated guidance and decision aids will facilitate ethical decision-making about XTx clinical trials. The innovative and timely decision aids will contain generalizable ethical principles for human subjects research protections and policy considerations regarding organ allocation that will apply to XTx clinical trials involving other organs. Future next steps include designing a study to test the influence of the decision aids on the choices of patients, IRBs, and transplant centers about XTx kidney clinical trials.

项目概要异种移植（XTx）是一种新颖的实验性治疗方法，涉及移植非人类器官由于缺乏用于移植的人体器官，XTx 可以帮助缓解这种情况。器官短缺是一个持续存在的公共卫生问题。 20 世纪 60 年代至 90 年代在美国进行，涉及黑猩猩肾脏、狒狒心脏和狒狒尽管 XTx 实验前景广阔，但由于科学和伦理原因，该实验于 20 世纪 90 年代末结束。如今，XTx 正在经历免疫抑制和基因组方面的科学进步。编辑技术降低了人畜共患疾病传播的风险，移植领域已做好准备。进行 XTx 临床试验，然后将研究结果转化为临床护理。但是，有可用的指南。进行 XTx 临床试验已经过时，不涉及 XTx 科学的进步，不考虑利益相关者的担忧，没有考虑器官分配政策变化的影响。拟议研究的目的是为转化确定适当的伦理和政策指导实体器官 XTx 临床试验的研究团队包括黑斯廷斯的国家生物伦理学领导者。中心、西北大学和罗格斯大学，以黑斯廷斯中心作为数据我们将对移植患者、移植支持者进行深入访谈，移植监管机构和人类受试者伦理监管机构，并从伦理和政策中获取意见咨询委员会由转化科学和生物伦理学专家组成，负责：(1) 评估 XTx 利益相关者对 XTx 临床试验的伦理和政策挑战的看法和担忧 (2) 发展； XTx 利益相关者决策辅助工具可帮助患者、居民和机构审查委员会评估、设计、分别监督 XTx 临床试验；以及 (3) 制定伦理转化建议 XTx 临床试验的更新指南和决策辅助将促进有关 XTx 临床的伦理决策。创新且及时的决策辅助工具将包含适用于人类受试者的普遍伦理原则。有关适用于 XTx 临床试验的器官分配的研究保护和政策考虑未来的下一步包括设计一项研究来测试决策辅助的影响。患者、IRB 和移植中心对 XTx 肾脏临床试验的选择。