Subgroup analyses have been widely

Subgroup analyses have been widely used to address treatment effect heterogeneity despite its limitations [20]. In particular, conventional subgroup analyses assess one characteristic at a time, which may not reflect the previous study to address the heterogeneity in our study population. While it is still challenging to find the truephenotypes that are responsible for the heterogene-ity, we believe that our research process: (1) discover-ing the target phenotype, (2) implementing a model for predicting the phenotype, and (3) conducting studies for identifying the optimal target population or exploring underlying mechanisms—is an efficient way of conduct-ing future studies and advancing personalised medicine. For example, our findings support the findings from a post hoc analysis of the SCARLET trial that reported an association between higher baseline thrombin generation biomarker levels and the effect of rhTM [9], by demon-strating that a subtype consisting of a high-dimensional coagulation profile could be a potential target of rhTM.