Trial Design in Critical Care Nutrition: The Past, Present and Future.

The specialty of nutrition in critical care is relatively modern, and accordingly, trial design has progressed over recent decades. In the past, small observational and physiological studies evolved to become small single-centre comparative trials, but these had significant limitations by today's standards. Power calculations were often not undertaken, outcomes were not specified a priori, and blinding and randomisation were not always rigorous. These trials have been superseded by larger, more carefully designed and conducted multi-centre trials. Progress in trial conduct has been facilitated by a greater understanding of statistical concepts and methodological design. In addition, larger numbers of potential study participants and increased access to funding support trials able to detect smaller differences in outcomes. This narrative review outlines why critical care nutrition research is unique and includes a historical critique of trial design to provide readers with an understanding of how and why things have changed. This review focuses on study methodology, population group, intervention, and outcomes, with a discussion as to how these factors have evolved, and concludes with an insight into what we believe trial design may look like in the future. This will provide perspective on the translation of the critical care nutrition literature into clinical practice.