Establishment and Validation of Serum Ferritin Reference Intervals Based on Real-World Big Data and Multi-Strategy Partitioning Algorithms

<b>Background/Objectives:</b> We aimed to establish and validate population-based reference intervals (RIs) for serum ferritin (SF) using an indirect, date-driven approach based on real-world laboratory data and to optimize partitioning strategies. <b>Methods:</b> SF results from 29,723 apparently healthy individuals who underwent health examinations at West China Hospital between 2020 and 2024 were retrospectively analyzed. SF was measured on a Roche Cobas e801 electrochemiluminescence immunoassay platform. After Box-Cox transformation, outliers were removed using an iterative Tukey method. Potential partitioning factors were evaluated, and data-driven age cut-points were explored using decision tree regression and verified with the Harris-Boyd criteria. RIs were estimated using nonparametric percentile methods and validated in an independent cohort of 2494 individuals. <b>Results:</b> SF concentrations were significantly higher in males than in females (<i>p</i> < 0.001). In females, SF showed a significant positive association with age (<i>r</i> = 0.466, <i>p</i> < 0.001), whereas no such association was observed in males. Decision tree analysis identified 50 years as the optimal age cut-off for females (R² = 0.2467). The final study-derived RIs were 98.02-997.78 µg/L for males, 10.30-299.55 µg/L for females ≤ 50 years, and 36.61-507.00 µg/L for females > 50 years. In the validation cohort, the study-derived RIs achieved pass rates of 93.83-94.72%, which were significantly higher than the manufacturer-provided RIs (37.12-73.97%, all <i>p</i> < 0.001). <b>Conclusions:</b> Using a large health examination database and a multi-step partitioning strategy, we established robust sex- and age-specific SF RIs on the Roche Cobas e801 platform for the local population. This work provides a reproducible, generalizable framework for indirect RI determination of other biomarkers.