Uncertain Translation, Uncertain Benefit and Uncertain Risk: Ethical Challenges Facing First‐in‐human Trials of Induced Pluripotent Stem (Ips) Cells

Abstract

The discovery of induced pluripotent stem (iPS) cells in 2006 was heralded as a major breakthrough in stem cell research. Since then, progress in iPS cell technology has paved the way towards clinical application, particularly cell replacement therapy, which has refueled debate on the ethics of stem cell research. However, much of the discourse has focused on questions of moral status and potentiality, overlooking the ethical issues which are introduced by the clinical testing of iPS cell replacement therapy. First-in-human trials, in particular, raise a number of ethical concerns including informed consent, subject recruitment and harm minimisation as well as the inherent uncertainty and risks which are involved in testing medical procedures on humans for the first time. These issues, while a feature of any human research, become more complex in the case of iPS cell therapy, given the seriousness of the potential risks, the unreliability of available animal models, the vulnerability of the target patient group, and the high stakes of such an intensely public area of science. Our paper will present a detailed case study of iPS cell replacement therapy for Parkinson's disease to highlight these broader ethical and epistemological concerns. If we accept that iPS cell technology is fraught with challenges which go far beyond merely refuting the potentiality of the stem cell line, we conclude that iPS cell research should not replace, but proceed alongside embryonic and adult somatic stem cell research to promote cross-fertilisation of knowledge and better clinical outcomes.

Challenges of clinical translation in nanomedicine: A qualitative study

“…Slow and scarce translational research is a global concern due to its adverse impact on the availability of affordable and effective treatment options. The financial, ethical, and regulatory challenges presented in this paper have been discussed extensively in the literature on translation of other cutting edge biotechnologies such as gene transfer, 5 cell therapy, [28][29][30][31] and regenerative medicine, [32][33] but our study is the first to actually investigate the experience of those involved in translational nanomedicine. This allowed us to understand the tensions underlying these challenges and to seek solutions which will be relevant for medical applications of any cutting edge biotechnology.…”

Ethical considerations and challenges in first-in-human research

“…123 However, obtainment of proxy consent from surrogate decision-makers or legally acceptable representatives is still a controversial option in FIH research and needs further consideration. 95 A question has been raised for the bioethics community concerning why the consent made by terminally ill patients to participate in FIH research are not acceptable, whereas their consent for other procedures, such as life-saving organ transplants, do-not-resuscitate requests, or estate wills, are. 54 …”

“…7 Even so, justification for the involvement of vulnerable individuals that is based solely on the promise of generalizable knowledge for future patients (social value), absent any prospect of personal medical benefits for research subjects, is contentious and needs rigorous considerations. 95 Furthermore, due to their participation in a nontherapeutic FIH study, the enrolled subjects may lose their eligibility status for a subsequent trial that may hold therapeutic benefits for them. 96 Less seriously ill patients whose degree of decisional vulnerability is less is thus proposed as an optional target population in some FIH research.…”

Ethics and Policy Issues for Stem Cell Research and Pulmonary Medicine

“…Should there be restrictions placed on enrolling those who are not able to provide consent because of age (ie, children) or limited cognitive capacity? [78][79][80] Obtaining informed consent may also be complicated by the need to convey complex information, such as the stem cell-based sources of the interventions being tested and the uncertainties of the related risks. Further, potential participants may be particularly vulnerable to hype, desperation, and the therapeutic misconception (not appreciating the diff erence between usual clinical care and research).…”