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

Educational Objective
To externally validate the Epic Sepsis Model (ESM) in the prediction of sepsis and evaluate its potential clinical value compared with usual care.
1 Credit CME
Key Points

Question  How accurately does the Epic Sepsis Model, a proprietary sepsis prediction model implemented at hundreds of US hospitals, predict the onset of sepsis?

Findings  In this cohort study of 27 697 patients undergoing 38 455 hospitalizations, sepsis occurred in 7% of the hosptalizations. The Epic Sepsis Model predicted the onset of sepsis with an area under the curve of 0.63, which is substantially worse than the performance reported by its developer.

Meaning  This study suggests that the Epic Sepsis Model poorly predicts sepsis; its widespread adoption despite poor performance raises fundamental concerns about sepsis management on a national level.

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.

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Article Information

Accepted for Publication: April 18, 2021.

Published Online: June 21, 2021. doi:10.1001/jamainternmed.2021.2626

Correction: This article was corrected on August 2, 2021, to fix an error in the number needed to evaluate presented in Table 2 and the Results.

Corresponding Author: Karandeep Singh, MD, MMSc, Department of Learning Health Sciences, University of Michigan Medical School, 1161H NIB, 300 N Ingalls St, Ann Arbor, MI 48109 (kdpsingh@umich.edu).

Author Contributions: Dr Singh had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Wong, Otles, Pestrue, Phillips, Penoza, Singh.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Wong, Otles, Ghous, Singh.

Critical revision of the manuscript for important intellectual content: Wong, Otles, Donnelly, Krumm, McCullough, DeTroyer-Cooley, Pestrue, Phillips, Konye, Penoza, Singh.

Statistical analysis: Wong, Otles, Donnelly, Krumm, McCullough, Singh.

Administrative, technical, or material support: Wong, Otles, Pestrue, Phillips, Konye, Penoza.

Supervision: Singh.

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.

Funding/Support: Mr Otles was supported by grant T32GM007863 from the National Institutes of Health. Dr Donnelly was supported by grant K12HL138039 from the National Heart, Lung, and Blood Institute.

Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 credit toward the CME of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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