Evaluating Large Language Models Against Clinical Assessment Frameworks for Early Sepsis Detection in the ICU
Timely recognition of sepsis remains difficult when early physiological abnormalities are subtle or incomplete. This study examined whether general-purpose large language models could discriminate sepsis risk from an initial ICU vital-sign snapshot as effectively as established clinical scoring approaches. We performed a retrospective benchmark using the deidentified PhysioNet Sepsis Prediction Dataset. The eligible cohort included 39,234 adults, of whom 2,733 were sepsis-positive. Two zero-shot language models and two modified clinical scores were evaluated on the same patients. Discrimination was measured by the area under the receiver operating characteristic curve (AUROC), with bootstrap confidence intervals and DeLong tests for paired comparisons. AUROC was 0.597 for GPT-5.5, 0.592 for modified NEWS2, 0.591 for Claude Sonnet 5, and 0.570 for modified SOFA. Neither language model differed significantly from modified NEWS2, whereas both produced higher AUROC values than modified SOFA. A pre-onset-only sensitivity analysis, restricted to patients whose snapshot preceded their first positive sepsis label (achieved median lead time 39 hours), showed all four estimators converging (AUROC 0.579– 0.591) with no significant pairwise differences, indicating the primary-analysis gap over SOFA was partly attributable to postonset records. A stricter analysis limited to a minimum 6-hour lead time reversed the ranking: the SOFA-derived score obtained the highest AUROC (0.597), with the LLMs and NEWS2-derived score converging lower (0.573–0.578), again with no significant pairwise differences. Their alerting behaviour was not interchangeable: GPT-5.5 produced a more balanced sensitivity-specificity profile, while Claude Sonnet 5 identified more positive cases at the cost of additional false alerts. These findings show that zero-shot language models can provide discrimination comparable to the strongest modified clinical score in this dataset. The modest absolute AUROC values, use of modified scores, and retrospective single-dataset design mean that the models should be considered complementary research tools, not stand-alone clinical detectors.