Informing Ethical Translation of Xenotransplantation Clinical Trials

项目总结 异种移植(XTx)是一种新的实验性治疗方法，它涉及到非人类器官的移植。 把动物变成人类。由于人体器官移植的稀缺性，XTx可以帮助缓解 器官短缺，这是一个持续的公共卫生问题。早期的实验异种移植是 从20世纪60年代到90年代在美国表演，涉及黑猩猩的肾脏，狒狒的心脏和狒狒 肝脏。尽管XTx实验前景看好，但由于科学和伦理的原因，XTx实验在20世纪90年代末结束了 挑战。今天，XTx正在经历一场复兴。免疫抑制与基因组研究进展 编辑技术降低了人畜共患病传播的风险。移植领域已经做好了准备 进行XTx临床试验，然后将结果转化为临床护理。但是，现有的指导原则适用于 进行XTx临床试验是过时的，不解决XTx科学上的进展，不占 考虑利益攸关方的关切，而不考虑对器官分配政策变化的影响。整体而言 拟议研究的目标是为翻译确定适当的伦理和政策指导 实体器官XTx临床试验。该研究团队包括黑斯廷斯家族的国家生物伦理学领袖 西北大学和罗格斯大学，黑斯廷斯中心作为数据 协调中心。我们将深入采访移植患者，移植临床医生， 移植调节器和人类受试者道德调节器，并从道德和政策中获得输入 由翻译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临床试验；以及(3)制定关于道德翻译的建议 XTx临床试验。更新的指导和决策辅助工具将促进关于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针对人类主体的可概括的伦理原则。 关于将适用于XTx临床试验的器官分配的研究保护和政策考虑 牵涉到其他器官。未来的下一步包括设计一项研究，以测试决策辅助对 患者、IRBs和移植的选择以XTx肾脏临床试验为中心。

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 However, available guidelines for conducting XTx clinical trials are outdated, do not address advances in the science of XTx, do not account for stakeholders’ concerns, and do not consider the impact on policy changes to organ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