The importance of considering the h

The importance of considering the heterogeneity in the study population and the treatment effects has been emphasised in recent years [6]. As shown in the analysis of multiple sepsis registries and RCTs [5], clinical phenotypes were correlated with host-response patterns and clinical outcomes, and simulations suggested the presence of heterogeneity in treatment effects across phenotypes. Thus, such heterogeneity may at least partially explain the underlying mechanisms of RCTs that failed to reveal significant benefit of therapies in critical care [18, 19]. Indeed, patients who met the inclusion criteria for the SCARLET trial accounted for 20–30% of the patients with rhTM target phenotype, suggesting that further studies are needed to investigate the effects of rhTM for sepsis. Additionally, the process of identifying the taget population to be treated is important and should be discussed in future costbenefit analyses of treatment strategies, even if a small proportion of patients can be treated effectively (as was the case in our study sample).