The Complex Ethics of First in Human Stem Cell Clinical Trials

Abstract

We applaud Dr. Hess for raising an issue of critical importance regarding Phase I clinical trials of novel stem cell (sc) transplants, which is the role that clinical efficacy endpoints should play in assuring the ethical design and conduct of such trials.1 In what follows, we highlight significant considerations, all interrelated, that can challenge efforts to incorporate ethically appropriate clinical efficacy endpoints in Phase I sc trials. First and foremost is the need to preserve the principal aim of safety in such trials. Second is the degree of difficulty researchers can face in trying to minimize the risks that Phase I sc trials pose to clinical volunteers. Third is the difficulty of knowing what should count as adequate pre-clinical data that warrant the launch of Phase I trials with realistic expectations for clinical efficacy. Finally, there is the challenge of not permitting those clinical efficacy measures to introduce unrealistic expectations of therapeutic benefit into the informed consent process. Throughout we will draw from ongoing research, including research at our own institution, that targets sc therapies for both Huntington’s disease (HD) and Amyotrophic Lateral Sclerosis (ALS).