Clinical and translational research necessarily involves some risks to human subjects. Moreover, early-phase research is conducted primarily to determine the safety of interventions that are potentially risky. Despite such inherent risks, research should not pose avoidable risks. Although considerable attention in the design and review of research focuses on considering its risks and benefits, this may be insufficient for robustly protecting the interests of those who decide to participate in clinical and translational research. Understanding the ethical obligation to maximize safety in clinical and translational research necessitates considering direct harms as well as duty to those who decide to participate. Given the clear ethical obligation to maximize safety in research, when appropriate, the science of safety should be more thoroughly integrated into the research enterprise.

Key words/concepts: human subjects research, research ethics, human subjects protection, risks and benefits, clinical research, translational research, science of safety