Machine Learning Interpretability Methods to Characterize the Importance of Hematologic Biomarkers in Prognosticating...

Early detection of sepsis in patients admitted to the emergency department (ED) is an important clinical objective as early identification and treatment can help reduce morbidity and mortality rate of 20% or higher. Hematologic changes during sepsis-associated organ dysfunction are well established and a new biomarker called Monocyte Distribution Width (MDW) has been recently approved by the US Food and Drug Administration for sepsis. However, MDW, which quantifies monocyte activation in sepsis patients, is not a routinely reported parameter and it requires specialized proprietary laboratory equipment. Further, the relative importance of MDW as compared to other routinely available hematologic parameters and vital signs has not been studied, which makes it difficult for resource constrained hospital systems to make informed decisions in this regard. To address this issue, we analyzed data from a cohort of ED patients (n=10,229) admitted to a large regional safety-net hospital in Cleveland, Ohio with suspected infection who later developed poor outcomes associated with sepsis. We developed a new analytical framework consisting of seven data models and an ensemble of high accuracy machine learning (ML) algorithms (accuracy values ranging from 0.83 to 0.90) for the prediction of outcomes more common in sepsis than uncomplicated infection (3-day intensive care unit stay or death). To characterize the contributions of individual hematologic parameters, we applied the Local Interpretable Model-Agnostic Explanation (LIME) and Shapley Additive Value (SHAP) interpretability methods to the high accuracy ML algorithms. The ML interpretability results were consistent in their findings that the value of MDW is grossly attenuated in the presence of other routinely reported hematologic parameters and vital signs data. Further, this study for the first time shows that complete blood count with differential (CBC-DIFF) together with vital signs data can be used as a substitute for MDW in high accuracy ML algorithms to screen for poor outcomes associated with sepsis.