Designing nutrition-based interventional trials for the future: addressing the known knowns

The consistent decline in critical illness mortality has a significant effect on trial design, whereby either an improbable effect sizes or large number of patients are required. The signal-to-noise ratio is of particular interest for the critically ill. When considering the potential signal, interventions need to match outcomes in regard to biological plausibility. Provision of nutrition is a complex decision with many underappreciated aspects of noise. However, a fundamental interaction is often not accounted for time. Working as a community to evolve trial design will be our challenge for nutrition interventions in the critically ill for the future.