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

• 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
• 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

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.

项目摘要 异种移植（XTX）是一种新型的实验治疗，涉及从非人类的移植器官 动物进入人类。由于人类器官缺乏移植，XTX可以帮助减轻 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植物是 从1960年代到1990年代在美国演出，涉及黑猩猩肾脏，狒狒心脏和狒狒 肝。尽管有巨大的希望，XTX实验由于科学和道德而于1990年代后期结束 挑战。如今，XTX正在进行文艺复兴。免疫抑制和基因组的科学进步 编辑技术减轻了人畜共患病传播的风险。移植场被置于 进行XTX临床试验，然后将发现转化为临床护理。但是，可用的指南 进行XTX临床试验的进行过时，不要解决XTX科学的进步，不要说明 利益相关者的担忧，并且不考虑对器官分配的政策变化的影响。总体 拟议研究的目的是确定适当的道德和政策指导 固体器官XTX临床试验。研究小组包括黑斯廷斯的国家生物伦理领导人 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的访谈， 移植监管机构和人类主体伦理监管机构，并从道德和政策中获得意见 咨询委员会完成了翻译科学和生物伦理专家的完成：（1）评估XTX 利益相关者对XTX临床试验的道德和政策挑战的看法和关注； （2）发展 XTX利益相关者的决策AIDS，可帮助患者，临床医生和机构审查委员会评估，设计， 并分别监督XTX临床试验； （3）关于道德翻译的发展建议 XTX临床试验。更新的指导和决策AIDS将促进有关XTX临床的道德决策 试验。创新且及时的决策辅助工具将包含针对人类主题的概括性原则 有关器官分配的研究保护和政策考虑因素，该考虑适用于XTX临床试验 涉及其他器官。未来的下一步措施包括设计一项研究以测试决策辅助的影响 患者，IRB和移植物的选择中心关于XTX肾脏临床试验。