Automated identification of patient subgroups: A case-study on mortality of COVID-19 patients admitted to the ICU

BACKGROUND: – Subgroup discovery (SGD) is the automated splitting of the data into complex subgroups. Various SGD methods have been applied to the medical domain, but none have been extensively evaluated. We assess the numerical and clinical quality of SGD methods. METHOD: – We applied the improved Subgroup Set Discovery (SSD++), Patient Rule Induction Method (PRIM) and APRIORI – Subgroup Discovery (APRIORI-SD) algorithms to obtain patient subgroups on observational data of 14,548 COVID-19 patients admitted to 73 Dutch intensive care units. Hospital mortality was the clinical outcome. Numerical significance of the subgroups was assessed with information-theoretic measures. Clinical significance of the subgroups was assessed by comparing variable importance on population and subgroup levels and by expert evaluation. RESULTS: – The tested algorithms varied widely in the total number of discovered subgroups (5-62), the number of selected variables, and the predictive value of the subgroups. Qualitative assessment showed that the found subgroups make clinical sense. SSD++ found most subgroups (n = 62), which added predictive value and generally showed high potential for clinical use. APRIORI-SD and PRIM found fewer subgroups (n = 5 and 6), which did not add predictive value and were clinically less relevant. CONCLUSION: – Automated SGD methods find clinical subgroups that are relevant when assessed quantitatively (yield added predictive value) and qualitatively (intensivists consider the subgroups significant). Different methods yield different subgroups with varying degrees of predictive performance and clinical quality. External validation is needed to generalize the results to other populations and future research should explore which algorithm performs best in other settings.