Table 1.

Summary of critical care nutrition study design in the past, present, and future.

	Past	Present	Future
Study methodology	Small physiological, observational, and single-centre comparative trials; poorly defined and underdeveloped processes	Large phase III trials (usually in the 1000s); a priori defined protocols, outcomes, and interim analyses	Sophisticated statistical techniques; larger sample sizes (tens of thousands); adaptive trial designs
Population	Small, specific populations often from specialist centres	General, heterogenic populations	Homogenous; selected based on anticipated response to nutrition intervention (e.g., malnourished); includes non-invasively ventilated cohorts
Intervention	Calories; early vs. late initiation; route of delivery e.g., gastric vs. jejunal, EN vs. PN, protein- vs. glucose-based PN, medium- vs. long-chain triglycerides and branched chain amino acids; immunonutrition	General interventions for general questions; focused only on the period in ICU	Synergistic; patient-specific; based on mechanisms; extension of interventions beyond ICU discharge considering illness trajectory
Outcomes	Calorie delivery; nitrogen balance; incidence of infection; mortality (but underpowered to show an effect in the latter)	Robust clinical outcomes such as mortality	Patient recovery; functional outcomes; valid surrogate markers

Abbreviations: EN = enteral nutrition; ICU = intensive care unit; PN = parenteral nutrition.