Procalcitonin measurement uncertainty around Sepsis-related decision thresholds: Monte Carlo modeling from a large-scale clinical laboratory dataset.

BACKGROUND: Procalcitonin (PCT) supports sepsis assessment and antimicrobial stewardship; however, the interpretive implications of measurement uncertainty (MU) near decision thresholds remain poorly defined. In this study, PCT MU was estimated across modules and patient-level results susceptible to threshold-adjacent reclassification were quantified. METHODS: Over 12 months, 554,570 PCT measurements were obtained in a high-throughput tertiary-care laboratory using seven equivalent Siemens Atellica IM modules on the same BRAHMS PCT immunoassay platform. MU was estimated using a Nordtest-based top-down approach, complemented by Monte Carlo simulation to model within-period imprecision and between-period analytical variation for each module. Top-down intervals were evaluated at the 0.50 and 2.00 ng/mL decision thresholds and at a supplementary 10.00 ng/mL reference level, whereas Monte Carlo intervals were calculated for the two thresholds. A high-level internal quality control (IQC) sensitivity analysis recalculated the reproducibility component near 10.00 ng/mL. RESULTS: Module-specific expanded MU ranged from 21.08% to 26.96%; pooled estimates were 24.22% in the primary analysis and 24.36% in the high-level IQC sensitivity analysis. The widest Monte Carlo-derived intervals were 0.34-0.66 ng/mL at 0.50 ng/mL, containing 2693 results below and 1376 above the threshold, and 1.37-2.63 ng/mL at 2.00 ng/mL, containing 935 below and 571 above. At 10.00 ng/mL, the pooled top-down interval was 7.58-12.42 ng/mL, containing 288 results below and 199 above the reference level. CONCLUSIONS: Module-specific and between-period analytical variation may contribute to measurement uncertainty in PCT results near decision thresholds. Threshold-adjacent results should be interpreted within the clinical context rather than as fixed categorical findings.