Informing Ethical Translation of Xenotransplantation Clinical Trials

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 However, available guidelines for conducting XTx clinical trials are outdated, do not address advances in the science of XTx, do not account for stakeholders’ concerns, and do not consider the impact on policy changes to organ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