Multicenter Prospective Validation of an Updated Proprietary Sepsis Prediction Model - PubMed (original) (raw)

Multicenter Study

. 2026 Feb 2;9(2):e260181.

doi: 10.1001/jamanetworkopen.2026.0181.

Danielle Currey 2 3, Megan Schwinne 4, Brenna Park-Egan 5, Sean Meyer 1, Andrew Gutting 1, Jie Cao 6 7, Sharaf Khan 8, Raymund Dantes 9, Tony Pan 4, Timothy Buchman 10, Karandeep Singh 6 7, Sivasubramanium V Bhavani 9 11, Patrick G Lyons 5, Michael W Sjoding 1, Yasir Tarabichi 2 3 12

Affiliations

Multicenter Study

Multicenter Prospective Validation of an Updated Proprietary Sepsis Prediction Model

Andrew Wong et al. JAMA Netw Open. 2026.

Abstract

Importance: The Epic Sepsis Model version 2 (ESM v2) is a widely implemented proprietary sepsis prediction model, but no multicenter, external validation of its performance has been reported to guide adoption and use.

Objective: To conduct a multicenter validation of the ESM v2 to compare performance against the original ESM v1, outline differences across heterogenous clinical sites, and compare model performance against clinician recognition of sepsis.

Design, setting, and participants: This prognostic study included adult inpatient encounters at 4 large US health systems between August 31, 2023, and March 11, 2025. At each site, data were collected for a consecutive period immediately following new model implementation. Data were analyzed from July 23 to August 19, 2025.

Main outcomes and measures: Sepsis was defined using Sepsis-3 clinical consensus criteria. Model discrimination was assessed using area under the receiver operating characteristic curve (AUROC) at the encounter level and prediction level with 4-hour, 12-hour, and hospitalization-wide time horizons. Performance against clinician recognition of sepsis was measured using antibiotics, lactate, and body culture orders.

Results: Of 227 091 inpatient encounters, 7401 (3.3%; median [IQR] age, 65 [54-75] years; 3359 [45.4%] female; 2.7% Asian; 24.6% Black; 64.6% White; 7.1% Hispanic ethnicity) met sepsis criteria and 219 690 (96.7%; median [IQR] age, 48 [33-65] years; 123 563 [56.2%] female; 2.5% Asian; 38.8% Black; 49.6% White; 9.6% Hispanic ethnicity) did not. At the encounter level, the AUROC ranged from 0.82 (95% CI, 0.81-0.83) to 0.92 (95% CI, 0.92-0.93) across study sites. At the prediction level with a 12-hour time horizon, the AUROC ranged from 0.75 (95% CI, 0.74-0.75) to 0.85 (95% CI, 0.85-0.85). Comparison against clinician recognition of sepsis yielded a minor decrease in performance, with the resulting encounter-level AUROC ranging from 0.80 (95% CI, 0.79-0.81) to 0.90 (95% CI, 0.89-0.90) across sites. Positive predictive values remained low, from 0.13 (95% CI, 0.13-0.14) to 0.26 (95% CI, 0.25-0.27), with a high number needed to evaluate and high alert burden.

Conclusions and relevance: In this prognostic study of a new sepsis prediction model, a multicenter prospective validation performed across 4 major US health systems found improved discrimination for the early prediction of sepsis but noted high institutional variability, low positive predictive value, and high alert burden.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Buchman reported receiving fess from Society of Critical Care Medicine (paid to institution) for serving as editor-in-chief of Critical Care Medicine and salary support from the US Government (paid to institution) for serving as a senior advisor to Biomedical Advanced Research and Development Authority outside the submitted work. Dr Singh reported receiving personal fees from Google for serving on a consumer health advisory panel outside the submitted work. Dr Lyons reported receiving personal fees from Society of Critical Care Medicine for serving as Associate Editor of Critical Care Medicine outside the submitted work. No other disclosures were reported.

Figures

Figure 1.

Figure 1.. Encounter-Level Discriminative Performance of the Epic Sepsis Model Version 2 Across Study Sites

Discriminative performance of the Epic Sepsis Model version 2 at the encounter-level was plotted across all possible model thresholds. The shaded region represents 95% confidence intervals for each performance statistic. NPV indicates negative predictive value; OHSU, Oregon Health & Sciences University; PPV, positive predictive value.

Figure 2.

Figure 2.. Dot Plot Showing Comparison of Epic Sepsis Model Version 2 and Version 1 Performance Before Sepsis-3 Positivity and Clinician Recognition

Discriminative performance of the Epic Sepsis Model version 2 and version 1 before Sepsis-3 positivity and before clinician recognition were plotted. Red and blue markers indicate the area under the receiver operating characteristic curve (AUROC) of each corresponding model and error bars represent 95% CIs generated with 1000 bootstrap resamples. Clinician recognition of sepsis was defined as the time of the earliest antibiotic, lactate, or body culture order prior to Sepsis-3 positivity, if present, and defaulted to time of sepsis positivity otherwise. OHSU indicates Oregon Health & Sciences University.

References

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