Early-stage research: Issues in design and ethics

Abstract

First-in-human and other early-stage research have several characteristics that require special attention with respect to ethics and human subjects' protections. Risks of harm, translational uncertainty, the ambiguities surrounding potential direct benefit, the need for long-term follow-up, the timing of the move from preclinical studies to the enrollment of human subjects, and the choice of first subjects all merit explicit and repeated consideration, beginning at the first stages of research design and continuing to the consent process and beyond. At least some regenerative medicine technologies also have additional characteristics that should be carefully addressed in the design and conduct of clinical research. These characteristics include: how regenerative medicine interventions are described, the likelihood of confusion between research and treatment (i.e., the therapeutic misconception), the challenge of comparing a novel biotechnological intervention with available alternatives, and a decisionmaking context that features a range of complex experimental interventions involving multiple scientific disciplines, often combining surgical and nonsurgical components and incorporating both standard and experimental aspects. This chapter considers how investigators and oversight bodies should address these characteristics when conceptualizing a line of translational research, designing and carrying out clinical trials, and seeking potential subjects' informed consent to early-stage regenerative medicine research.