Assessing the risks and benefits of early-phase clinical trials presents a persistent challenge for research ethics committees. These trials often lack direct, supporting evidence of clinical safety and efficacy, requiring ethics reviewers to evaluate a complex, heterogeneous body of preclinical and mechanistic evidence. The Preclinical Assessment for Translation to Humans (PATH) framework provides a systematic method for analyzing the strength of supporting evidence for early-phase trials. PATH structures the evaluation of risks and benefits into a series of mechanistic steps, guiding ethics committees through a transparent and reasoned assessment of the evidence linking molecular effects to clinical outcomes. However, applying PATH can be time-intensive and complex. In this article, we propose a streamlined approach-ten key questions that ethics committees can use to apply PATH toward a systematic evaluation of the translational chain of evidence in early-phase trials. By incorporating this approach, ethics committees can fulfill their duty to protect research participants to ensure that early-phase trials are ethically and scientifically grounded.
Hey et al. (Fri,) studied this question.