Faculty Bibliography

Expanded research opportunities in deceased humans require ongoing ethical inquiry.

The standard treatment for end-stage organ failure is transplantation, but demand for organs has always vastly outstripped supply. Discussions are ongoing about the feasibility of addressing the organ shortage through measures like increasing organ donations, improving post-transplant outcomes, and xenotransplantation. This paper examines the rationale, risks, and costs of xenotransplantation, such as xenozoonoses, creating a new form of industrialized animal farming, abandoning animal ethics principles, and the opportunity costs of investing finite research dollars in xenotransplantation instead of investing in more viable strategies. Alternative strategies that can ethically and effectively address the demand for heart, kidney, and other transplants are recommended: Improving disease prevention and management to reduce demand for transplant organs, improving transplantation methods, and systemic changes to donor policies and organ recovery methods to increase overall supply. Upon careful exploration of the full landscape of organ transplantation, it is considered whether these alternative strategies that do not impose the definite harms and significant risks of xenotransplantation are the most ethical and effective means to increase life-saving options and improve clinical outcomes for patients in organ failure.

BACKGROUND:Cardiac allotransplantation is the optimal treatment for end-stage heart failure. However, organ supply remains the principal issue impacting patients. Pediatric patients present unique challenges resulting in long wait-list times and increased mortality. Donation after circulatory death with normothermic regional perfusion represents a method to increase the number of available organs in this population. METHODS:Multi-institutional expert consultation was sought to outline extant technical, ethical, and logistical issues with regard to normothermic regional perfusion cardiac donation techniques. Specific advantages in the pediatric population are highlighted, as well as technical considerations resulting in successful organ procurement. RESULTS:Utilization of donation after circulatory death organs following normothermic regional perfusion in the United States is increasing and offers advantages to the pediatric heart failure population. Ethical reservations both nationally and abroad persist, namely pertaining to cerebral blood flow. This has led to variation in perception and utilization of normothermic regional perfusion, contributing to a discrepancy between donor and recipient locations. Procurement techniques and variations are described, with introduction into program planning and protocol development. Training in technical aspects of the procedure is paramount for both the surgeon and support staff to construct a successful program, along with transparent protocols to mitigate ethical concerns. CONCLUSIONS:Normothermic regional perfusion is relevant following donation after cardiac death in the pediatric population. Ethical and technical challenges remain in concert with substantial domestic and international variation. Standardization of technique may serve to increase future use and increase the number of available hearts for transplant, reducing pediatric mortality.

Use of normothermic regional perfusion (NRP) to enable organ reconditioning and assessment in donation after circulatory determination of death (DCD) is controversial. We conducted a scoping review of peer-reviewed articles, news media, legal literature, and professional society position statements addressing ethical and/or legal issues in use of NRP in controlled DCD from January 1, 2005 to January 5, 2024. Thematic analysis, assessing the four principles of bioethics (autonomy, beneficence, non-maleficence, and justice) and sub-themes identified within each, was conducted for the 112 publications meeting inclusion criteria. More than 30 publications addressed the topic in each of 2022 and 2023, versus ≤6 per year previously. Non-maleficence was the most frequently addressed bioethical principle (111/112 publications), and most varied, with 14 subthemes. Attitudes towards NRP differed by type of NRP: Of 72 publications discussing thoracoabdominal NRP, 22 (30.6%) were 'In Favor', 39 (54.2%) 'Neutral', and 11 (15.3%) 'Against'; of 44 discussing abdominal NRP, 23 (52.3%) were 'In Favor', 20 (45.5%) 'Neutral', and 1 (2.3%) 'Against'. Attitudes differed by authors' country, degree, and affiliation, and by clinical focus of the publishing journal. Overall, our review shows the ethical and legal issues raised by NRP remain unresolved, and debate centered on non-maleficence.

OBJECTIVE/UNASSIGNED:Individuals who work on health data systems and services are uniquely positioned to understand the risks of health data collection and use. We designed and conducted a survey assessing the perceptions of those who work with health data around health data consent, sharing, and privacy practices in healthcare and clinical research. METHODS/UNASSIGNED:tests and ordinal logistic regression. RESULTS/UNASSIGNED:Most of our respondents (61.7%) reported that they would trust people to use their health data across various sectors, but more respondents trusted those working in academic medical research (86.5%) and healthcare offices (89.9%) compared to those working in industry (68.2%). Despite this reported trust, a strong majority believed that individuals should have complete control over their health data (97.3%), specific consent should be obtained for each use of their health data (92.0%), and that there should be higher standards of consent and privacy for health records data than other types of data (93.7%). CONCLUSIONS/UNASSIGNED:Based on our findings, we might infer that people who work with health data generally trust institutions across sectors to protect their health data. However, many would prefer to have complete control over who has access to their health data and how it is used. These insights should be explored further through qualitative studies.

Research institutions often lack policies addressing the risks and benefits of enrolling "invested parties" such as investigators, research staff, and patient, caregiver, and community representatives (groups most affected by a disease or intervention) in studies where they have direct involvement. Invested parties may have both strong motivations to study the condition or intervention and to participate as study subjects. More guidance is needed to promote appropriate access to research participation and mitigate potential risks. This article addresses the gap in guidance by presenting an ethical framework and practical guidelines for the enrollment of invested parties. Drawing from experiences with the Researching COVID to Enhance Recovery (RECOVER) Initiative, a large multisite observational cohort study, we argue that invested parties should not be categorically excluded from enrollment in their own research studies if certain criteria are met and appropriate safeguards are in place. We underscore the need to balance inclusion with fairness, promote valid voluntary informed consent, ensure data privacy, protect scientific validity, and mitigate unique risks to invested parties as participants. Additionally, we recommend regular reporting and empirical assessment to evaluate the impact of enrolling invested parties on participants and study outcomes.

This manuscript reports on a landmark symposium on the ethical, legal and technical challenges of xenotransplantation in the UK. King's College London, with endorsement from the British Transplantation Society (BTS), and the European Society of Organ Transplantation (ESOT), brought together a group of experts in xenotransplantation science, ethics and law to discuss the ethical, regulatory and technical challenges surrounding translating xenotransplantation into the clinical setting. The symposium was the first of its kind in the UK for 20 years. This paper summarises the content of the expert lectures showcasing the progress which has been made in xenotransplantation including-the history of xenotransplantation, advances in gene edited animals and progress towards clinical xenotransplantation. We then set out the ethical and legal issues still to be resolved. Finally, we report the themes of the roundtable discussion highlighting areas of consensus and controversy. While the detail of the legal discussion was directed towards the UK, the principles and summary reported here are intended to be applicable to any jurisdiction seeking to implement clinical xenotransplantation.