Do established comorbidity scores predict in-hospital mortality equally well in women and men? A nationwide validation in 166.7 million German inpatient cases, 2010-2024

Objectives. To determine whether three established comorbidity scores (Charlson Comorbidity Index, Elixhauser Comorbidity Sum, van Walraven Score), applied with a single formula to both sexes, are equally well calibrated and equally discriminating in women and men, and whether any difference reaches a pre-specified threshold of clinical relevance. Design. Population-based retrospective cohort study; external validation of three pre-existing prediction models (TRIPOD Type 4) with sex-stratified evaluation. The analysis plan was fixed in the time-stamped Research Data Centre submission syntax before any aggregated data existed. Setting. Germany; complete national enumeration of acute somatic Diagnosis-Related Group (DRG)-billed adult inpatient cases, reporting years 2010 to 2024. Participants. 166 693 491 adult inpatient cases meeting a pre-specified nine-step eligibility filter. Main outcome measures. In-hospital mortality. Primary axis: calibration (calibration-in-the-large, CITL; calibration slope; observed mortality per score quintile). Secondary axis: discrimination (area under the receiver operating characteristic curve, AUC). Pre-specified thresholds: between-sex slope difference of at least 0.05, absolute AUC difference of at least 0.01. Results. Calibration-in-the-large was effectively perfect in both sexes (|CITL| [≤] 0.0004). The scores diverged in how prediction kept pace with rising risk, and in opposite directions for women and men: for the Charlson index the calibration slope was 0.968 in men and 1.034 in women (difference 0.066), with smaller differences for the Elixhauser-Sum (0.039) and the van Walraven Score (0.029). At the same score quintile, observed mortality was higher in men at most quintiles, with a maximum risk ratio of 1.21 (95 % CI 1.20 to 1.22); two van Walraven quintiles ran the other way (0.87 and 0.97). Differences in discrimination were small (random-effects AUC difference: Charlson -0.0076, 95 % CI -0.0095 to -0.0057; Elixhauser-Sum +0.0074; van Walraven -0.0026). Conclusions. Applied with a single formula to both sexes, three established comorbidity scores are calibrated differently in women and men, whereas their discrimination differs only marginally. Because these scores are reused at scale in research and in risk-adjusted mortality comparisons between hospitals, a systematic difference in calibration does not average out. This supports sex-specific recalibration. The downstream effect on hospital benchmarking is not yet quantified and should not be presumed negligible. Study registration. OSF DOI 10.17605/OSF.IO/P3QAW.