Efficiency of a Multi-step Screening and Enrichment Process for Prospective Sepsis Cohort Enrollment
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Background
Host response and biomarker research to advance sepsis therapeutics requires well-characterized cohorts with longitudinal biospecimens across a range of hosts and infections. Automated screening based on SIRS criteria is sensitive but nonspecific and identifies more candidates than research teams can approach, sample, and follow longitudinally. We evaluated a structured enrichment review by non-physician study staff, done after automated screening in a hospital-wide prospective sepsis cohort.
Methods
The CISID cohort is a prospective observational study of hospitalized patients with suspected sepsis, enrolling adults from the ED, inpatient wards, and ICUs at a tertiary academic medical center. Patients were identified through: (1) automated electronic health record screening for two or more SIRS criteria with a 24-hour lookback, documentation of microbiologic culture or PCR, and receipt of a new antibiotic; (2) a sepsis enrichment step of structured chart review by trained non-physician study staff; and (3) discussion with the primary clinical team. Enrolled patients underwent physician adjudication into four diagnostic categories. To evaluate the enrichment step, we analyzed all patients screened during a 9-week period, assigned a composite “sepsis-likely” variable (CDC Adult Sepsis Event criteria or ICD-10 code R65.20/R65.21 within 48 hours before or after screening), and assessed mortality across each stage of screening. We also assessed concordance of the composite with physician adjudication among enrolled patients.
Results
From November 2023 through February 2026, 4,318 patients screened in through EHR-based automated screening; 1,220 (28%) were flagged for enrollment, and 288 were enrolled. Physician adjudication classified 209 (73%) as sepsis, 46 (16%) as infection without sepsis, 14 (5%) were classified as undifferentiated critical illness, and 19 (6.6%) as non-infectious sepsis mimics. Patients with sepsis were severely ill (median SOFA score, 9; ICU admission, 80%; shock, 48%), and 51% were immunocompromised; mortality was 14% in hospital and 27% at 90 days. In a 9-week sample of 907 screened encounters, 21% of those deferred and 70% of those flagged for enrollment met the sepsis-likely composite, a 3.3-fold increase in prevalence after structured study team review.
Conclusions
A brief structured enrichment review after automated screening tripled the prevalence of EHR-based sepsis indicators among patients selected for enrollment, while concentrating enrollment efforts on roughly one-quarter of screened-in patients in this hospital-wide, all-source suspected-sepsis cohort. This approach may help prospective cohorts direct limited biospecimen resources toward patients most informative for host-response and biomarker research.
