Uncertainty about populations, interventions, comparators, effect size, and heterogeneity of treatment effect, applies to all clinical trials, but it particularly affects trials that test the effectiveness of interventions during epidemics. Another major challenge to conducting clinical trials during fast-moving epidemics is the lead-time needed to commence them. This presentation will discuss adaptive trial design as well as how such trials can deal with uncertainty and be implement-ready (but modifiable) prior to an epidemic.