• Manu Shankar-Hari and Gordon D Rubenfeld.
• Guy's and St Thomas' NHS Foundation Trust, ICU Support Offices, 1 Floor, East Wing, St Thomas' Hospital.
• Curr Opin Crit Care. 2019 Oct 1; 25 (5): 489-497.

Purpose Of ReviewSepsis and acute respiratory distress syndrome (ARDS) are two heterogenous acute illnesses where numerous RCTs have indeterminate results. We present a narrative review on the recent developments in enriching patient populations for future sepsis and ARDS trials.Recent FindingsMany researchers are actively pursuing enrichment strategies to reduce heterogeneity to increase the sensitivity of future trials. Enrichment refers to the use of measurable patient characteristics, known before randomisation, to refine trial populations. Biomarkers could increase the diagnostic certainty of sepsis, whereas chest radiology training to enhance reliability of interpretation and stabilisation period of mechanical ventilation have been considered to increase the diagnostic certainty of ARDS. Clinical and biomarker data analyses identifies four to six sepsis clinical phenotypes and two ARDS clinical phenotypes. Similarly, leukocyte gene expression data identifies two to four sepsis molecular phenotypes. Use of a test-dose identifies ARDS subpopulations who are likely to benefit from higher PEEP. Early-phase trials report how a biomarker that is altered by the intervention, such as lymphocyte count for recombinant interleukin-7 therapy and higher check point inhibitor expression for anti-check point treatments in sepsis, could identify a higher treatment effect population for future trials.SummaryEnrichment reduces heterogeneity and will enhance the sensitivity of future trials. However, enrichment, even when it identifies more homogenous populations, may not be efficient to deploy in trials or clinical practice.

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