Real-world effects of a sepsis early detection model integrated into clinical workflow: a quasi-experimental study

Background: Sepsis is a life-threatening condition in which delayed recognition and treatment are associated with increased mortality. While predictive models such as Epic’s Early Detection of Sepsis Model (ESM) were developed to support early intervention, their real-world effects after integration into clinical workflows remain difficult to evaluate. Objectives: To evaluate the real-world effects of ESM integrated into clinical workflow on clinical outcomes, antibiotic use, and harm-benefit tradeoffs. Methods: We conducted a quasi-experimental study in a single healthcare system using encounter-level data from inpatient settings. Inpatient mortality, prolonged hospitalization, antibiotic use, and sepsis prevalence (defined by EHR) were compared between the pre-acquisition period (3 June 2023 to 24 June 2024) and the online period (21 August 2024 to 26 December 2024) when the model became visible to clinicians. We also applied a counterfactual framework using models trained on pre-acquisition data to estimate expected outcomes without ESM and to quantify harms related to overtreatment and delayed treatment. Results: Among 89,469 encounters, 75,215 occurred during the pre-acquisition period and 14,254 during the online period. In unadjusted analyses, inpatient mortality, prolonged hospitalization, antibiotic use, and EHR-defined sepsis proportion all decreased during the online period (all p≤0.006). In the counterfactual analyses, observed outcomes were lower than expected without ESM for mortality (1.21% vs 1.94%; p<0.001), prolonged hospitalization (5.56% vs 8.14%; p<0.001), and antibiotic use (43.52% vs 47.74%; p<0.001). False positive harm (37.72% vs 42.31%; p<0.001) was also lower than expected. Conclusions: Integration of ESM into clinical workflow was associated with improved patient outcomes, reduced antibiotic use, and decreased harm from overtreatment, without evidence of increased harm from delayed treatment, supporting a positive net clinical benefit and the safety and effectiveness of ESM under Software as a Medical Device principles.