External Validation of a Widely Implemented Proprietary Sepsis Prediction Model in Hospitalized Patients

Abstract

Importance: The Epic Sepsis Model (ESM), a proprietary sepsis prediction model, is implemented at hundreds of US hospitals. The ESM's ability to identify patients with sepsis has not been adequately evaluated despite widespread use.

Objective: To externally validate the ESM in the prediction of sepsis and evaluate its potential clinical value compared with usual care.

Design, setting, and participants: This retrospective cohort study was conducted among 27 697 patients aged 18 years or older admitted to Michigan Medicine, the academic health system of the University of Michigan, Ann Arbor, with 38 455 hospitalizations between December 6, 2018, and October 20, 2019.

Exposure: The ESM score, calculated every 15 minutes.

Main outcomes and measures: Sepsis, as defined by a composite of (1) the Centers for Disease Control and Prevention surveillance criteria and (2) International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnostic codes accompanied by 2 systemic inflammatory response syndrome criteria and 1 organ dysfunction criterion within 6 hours of one another. Model discrimination was assessed using the area under the receiver operating characteristic curve at the hospitalization level and with prediction horizons of 4, 8, 12, and 24 hours. Model calibration was evaluated with calibration plots. The potential clinical benefit associated with the ESM was assessed by evaluating the added benefit of the ESM score compared with contemporary clinical practice (based on timely administration of antibiotics). Alert fatigue was evaluated by comparing the clinical value of different alerting strategies.

Results: We identified 27 697 patients who had 38 455 hospitalizations (21 904 women [57%]; median age, 56 years [interquartile range, 35-69 years]) meeting inclusion criteria, of whom sepsis occurred in 2552 (7%). The ESM had a hospitalization-level area under the receiver operating characteristic curve of 0.63 (95% CI, 0.62-0.64). The ESM identified 183 of 2552 patients with sepsis (7%) who did not receive timely administration of antibiotics, highlighting the low sensitivity of the ESM in comparison with contemporary clinical practice. The ESM also did not identify 1709 patients with sepsis (67%) despite generating alerts for an ESM score of 6 or higher for 6971 of all 38 455 hospitalized patients (18%), thus creating a large burden of alert fatigue.

Conclusions and relevance: This external validation cohort study suggests that the ESM has poor discrimination and calibration in predicting the onset of sepsis. The widespread adoption of the ESM despite its poor performance raises fundamental concerns about sepsis management on a national level.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Donnelly reported receiving grants from the National Institutes of Health, National Heart, Lung, and Blood Institute K12 Scholar during the conduct of the study; and personal fees from the American College of Emergency Physicians as an editor of Annals of Emergency Medicine outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Threshold Performance Plots for the Epic Sepsis Model at the Hospitalization Level

The distribution of predictions is displayed at the bottom. NPV indicates negative predictive value; PPV, positive predictive value. In the PPV plot, the blue-shaded region refers to the percentage of patients classified as positive. In the NPV plot, the blue-shaded region refers to the percentage of patients classified as negative.

Figure 2.. Distribution of Alert Times Based on an Epic Sepsis Model Score Threshold of 6 or Higher

A, All alerts. B, Alerts in the 24 hours prior to the outcome. The first alert is highlighted in orange. Each point represents a hypothetical alert; no actual alerts were generated. Forty randomly selected patients who experienced sepsis and met the alerting threshold of 6 are shown here.