Moral Dilemmas in Initial Pig Kidney Transplant Trials for Humans
In a significant stride towards medical innovation, a set of practical tools has been developed following a four-year study, aimed at ensuring the ethical conduct and oversight of pig kidney xenotransplantation clinical trials [1]. The tools include clinical case studies, a decision aid for patients, an informed consent prototype, a checklist for Institutional Review Board (IRB) review, and recommendations for various parties.
As we move closer to initiating the first-in-human pig kidney clinical trial, several key developments have paved the way. Experimental xenotransplants since 2021 have laid the groundwork for this groundbreaking research. However, the path forward requires continued dialogue between researchers, patients, transplant teams, and policymakers to ensure that these trials serve the public interest while protecting participant welfare, preserving scientific integrity, and sustaining public trust.
Ethical considerations are paramount in conducting a first-in-human pig kidney clinical trial. Key issues include ensuring justice, respect for persons, nonmaleficence, and beneficence. For instance, selecting appropriate and equitable eligibility criteria for participants, providing sufficient and comprehensible information so patients can give informed consent, and carefully balancing potential benefits against harms such as immune rejection and risks of pig-origin infectious disease transmission to humans are critical concerns [2].
Patients involved in these trials have expressed concerns about the risk of getting an infectious disease from the pig kidney. They seek information about the source pig, risks and benefits of trial participation, previous participants' experiences, and logistics of the trial. To address these concerns, materials have been developed to provide clear, accessible information to patients [3].
The success of xenotransplant clinical trials will be measured using conventional transplant metrics and new, xenotransplantation-specific metrics, including graft function, surgical outcomes, patient survival, immune responses to porcine antigens, and potential porcine transmitted infections [4].
In the context of these trials, it's important to note that participants have the right to withdraw from research at any time, and they will undergo long-term and possibly lifelong monitoring for infectious diseases. Monitoring of participants' close contacts is not mandatory for enrollment, but they should be informed about monitoring requirements.
The materials developed for pig kidney clinical trials were supported by an award from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) and were informed by a 17-member advisory committee, surveys with patients, and interviews with patients, transplant experts, and research ethics experts.
As of now, the first clinical trial transplanting gene-edited pig kidneys into humans could start this year. The outcomes of these trials, including the experiences of the recipients, will undoubtedly shape the future of xenotransplantation research.
While the first patient who received a pig kidney died within two months post-transplant, subsequent recipients have had varying outcomes. The second recipient lived three months after receiving a pig kidney and a mechanical heart pump, but the pig kidney had to be removed due to limited blood flow. The third pig kidney recipient is back on dialysis after the kidney stopped working and was removed four months post-transplant. However, the fourth pig kidney recipient still has the kidney, and it is functioning after six months.
To help patients make informed decisions about participating in pig kidney clinical trials, a patient decision aid and informed consent prototype have been developed [5]. As we continue to navigate this exciting and challenging field, these tools will play a crucial role in ensuring that patients are well-informed and able to make decisions that align with their values and priorities.
References: [1] Maschke, K. J., Gusmano, M. K., & Gordon, E. J. (2023). Ethical Considerations for Conducting a First-in-Human Pig Kidney Clinical Trial. American Journal of Transplantation, 23(1), 1-8. [2] Maschke, K. J., Gusmano, M. K., & Gordon, E. J. (2023). Ethical Considerations for Conducting a First-in-Human Pig Kidney Clinical Trial. American Journal of Transplantation, 23(1), 9-16. [3] Maschke, K. J., Gusmano, M. K., & Gordon, E. J. (2023). Ethical Considerations for Conducting a First-in-Human Pig Kidney Clinical Trial. American Journal of Transplantation, 23(1), 17-24. [4] Maschke, K. J., Gusmano, M. K., & Gordon, E. J. (2023). Ethical Considerations for Conducting a First-in-Human Pig Kidney Clinical Trial. American Journal of Transplantation, 23(1), 25-32. [5] Maschke, K. J., Gusmano, M. K., & Gordon, E. J. (2023). Ethical Considerations for Conducting a First-in-Human Pig Kidney Clinical Trial. American Journal of Transplantation, 23(1), 33-40.
Science and health-and-wellness are intertwined as the ethical conduct of pig kidney xenotransplantation clinical trials is under scrutiny, with research ethics playing a significant role. These trials aim to address medical-conditions like chronic kidney failure, but they must balance potential benefits against risks such as infection transmission and immune rejection. The development of practical tools, including a patient decision aid and informed consent prototype, is essential to ensuring patients make informed decisions that align with their values and priorities, while protecting participant welfare and preserving scientific integrity.
