Early-Phase Clinical Trials of Bio-Artificial Organ Technology: A Systematic Review of Ethical Issues

Abstract

Regenerative medicine has emerged as a novel alternative solution to organ failure which circumvents the issue of organ shortage. In preclinical research settings bio-artificial organs are being developed. It is anticipated that eventually it will be possible to launch first-in-human transplantation trials to test safety and efficacy in human recipients. In early-phase transplantation trials, however, research participants could be exposed to serious risks, such as toxicity, infections and tumorigenesis. So far, there is no ethical guidance for the safe and responsible design and conduct of early-phase clinical trials of bio-artificial organs. Therefore, research ethics review committees will need to look to related adjacent fields of research, including for example cell-based therapy, for guidance. In this systematic review, we examined the literature on early-phase clinical trials in these adjacent fields and undertook a thematic analysis of relevant ethical points to consider for early-phase clinical trials of transplantable bio-artificial organs. Six themes were identified: cell source, risk-benefit assessment, patient selection, trial design, informed consent, and oversight and accountability. Further empirical research is needed to provide insight in patient perspectives, as this may serve as valuable input in determining the conditions for ethically responsible and acceptable early clinical development of bio-artificial organs.

Advances in Recellularization of Decellularized Liver Grafts with Different Liver (Stem) Cells: Towards Clinical Applications

“…Drug authorities such as the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) provide well defined and strict guidelines for pharmaceutical agents, but not cell-based bio-artificial organs such as decellularized liver grafts. Jongh et al identified prominent themes to be considered for building clinical and ethical guidelines [112]. Defining cell source, risk-benefit assessment, criteria for patient selection, design of the trial, informed consent, oversight, and accountability issues related to cell-based bio-artificial organs (e.g., recellularized liver grafts) potentially benefit from clinical trials in adjacent fields such as cell therapy.…”

Clinical Translation of Bio-Artificial Pancreas Therapies: Ethical, Legal and Psychosocial Interdisciplinary Considerations and Key Recommendations

“…A recently published systematic review highlighted the ethical challenges of conducting early phase clinical trials of bioartificial organs [ 24 ]. Of most relevance to the clinical translation of this therapy for Type 1 Diabetes patients are 1) the source of the various cells used 2) recipient selection 3) informed consent and 4) access and justice considerations.…”

“…First, where hybrid products combine components made from cells and tissues (biomaterial) from different sources, each source (allogenic stem cells, deceased donor human islet cells and xenogeneic cells) will come with its own set of ethical considerations [ 24 ]. We explore this in more detail in Part 2 of this paper.…”

“…Second, in the early phases of clinical translation, like with many novel therapies, not all Type 1 Diabetes patients may be eligible for hybrid beta-cell replacement therapy. This therapy requires an invasive and potentially irreversible surgical procedure, and the therapy may interact and integrate with the body, with unknown potential harms and complications [ 24 ]. Yet this is not immediately lifesaving.…”

Ethische Abwägungen und Rückfragen zu Xenotransplantationen

“…Abgesehen von der medizintechnologischen Hoffnung auf künstliche Organe ist vor allem an Ersatzorgane auf der Basis humaner pluripotenter Stammzellen zu denken. Neuere Forschungserfolge der humanen Stammzellforschung lassen diese Option auf Dauer als durchaus realistisch erscheinen ( 13 S. 221, 19 ).…”