Fig. 1

a Clinical decision-making and RCTs operate on the hypothesis that an individual or population at risk is administered a therapeutic intervention that leads to a salutary biological response and a better health outcome (gray). Biomarkers (BM; orange) are used to monitor therapeutic responses or to define subsets of the population most likely to benefit from the intervention (Rx). b RCTs in the critical care nutrition field have assumed homogeneous (blue) nutritional risk, and they have not exploited biomarkers (red interrogation mark) to target patients at risk or to time nutritional interventions. Outcomes have been equivocal or difficult to interpret. c ICU patients exhibit metabolic heterogeneity (mixed colors), and multidimensional assays (bar codes) are best to capture the patients’ endotypes (e.g., blue) that predict clinical responses to nutrition support (red plus sign). Multidimensional biomarkers can be used to limit enrollment to those patients most likely to benefit (blue) or to enrich the results by classifying patients during post hoc analyses. Biomarker panels can be generated using new omics technologies that measure biological properties that are highly linked to nutrition and metabolism. Primary candidates are genomic, transcriptomic, epigenomic, and microbiome-based assays, which can then be reduced and implemented in non-invasive point-of-care assays