Informing Ethical Translation of Xenotransplantation Clinical Trials

项目摘要 异种移植（XTx）是一种新型的实验性治疗方法，涉及非人类器官移植 动物变成人类。由于用于移植的人体器官稀缺，XTx可以帮助缓解 器官短缺，这是一个持续的公共卫生问题。早期的异种移植实验 1960年代至1990年代在美国进行，涉及黑猩猩肾脏，狒狒心脏和狒狒 肝脏尽管有很大的希望，XTx实验在20世纪90年代末由于科学和道德原因而结束。 挑战如今，XTx正在经历一场复兴。免疫抑制与基因组学的科学进展 编辑技术降低了人畜共患病传播的风险。移植领域已经准备好 进行XTx临床试验，然后将结果转化为临床护理。然而，现有的指导方针， 进行XTx临床试验是过时的，不解决XTx科学的进步，不考虑 我们的研究只考虑持份者的关注，并没有考虑器官分配政策改变的影响。整体 拟议研究的目的是确定适当的伦理和政策指导， 实体器官XTx临床试验。该研究小组包括黑斯廷斯国家生物伦理学领导人 中心，西北大学和罗格斯大学，黑斯廷斯中心作为数据 协调中心。我们将对移植患者、移植临床医生进行深入访谈， 移植监管机构和人类受试者伦理监管机构，并从伦理和政策部门获得意见 由转化科学和生物伦理学专家组成的咨询委员会：（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）制定 XTx利益相关者决策辅助工具，帮助患者、临床医生和机构审查委员会评估、设计、 和监督XTx的临床试验，分别;和（3）制定建议的伦理翻译， XTx临床试验。更新的指南和决策辅助工具将促进有关XTx临床的伦理决策 审判创新和及时的决策辅助工具将包含适用于人类受试者的可推广伦理原则 适用于XTx临床试验的关于器官分配的研究保护和政策考虑 涉及其他器官。未来的下一步包括设计一项研究，以测试决策辅助工具对 患者、IRB和移植中心对XTx肾脏临床试验的选择。

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 However, available guidelines for conducting XTx clinical trials are outdated, do not address advances in the science of XTx, do not account for stakeholders’ concerns, and do not consider the impact on policy changes to organ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.