Application of the Hoffmann, Bhattacharya, nonparametric test, and Q-Q plot methods for establishing reference intervals from laboratory databases

Reference intervals (RIs) are vital for interpreting laboratory biomarkers and enabling clinical decision-making. Among various RI-estimation methods, we explored the application value of Hoffmann, Bhattacharya, nonparametric test, and Q-Q plot methods for estimating the RI of urea, creatinine, and uric acid (UA). This cross-sectional study collected patient data recorded between January 2020 and April 2022 at the Chongqing University Central Hospital Laboratory Information System. The RIs of urea, creatinine, and UA levels were established using the Hoffmann, Bhattacharya, nonparametric, and Q-Q plot methods, and RI differences with different computational methods were verified using the reference change value (RCV%) of biological variability. We included 16,474 and 123,570 patients in the physical examination and clinical groups, respectively. In the clinical group, differences in the RI upper limit of analytes with the four methods (excluding the Q-Q plot method) were within the permissible RCV% range; only the nonparametric test produced an RI of urea with the lower limit within the permissible RCV% range. In the physical examination group, the relative RI differences among the four methods (excluding the lower limit of RI obtained using the Q-Q plot) were all within the acceptable RCV% range; the relative deviation of the RI of UA with the four methods was within the acceptable RCV% range (excluding the lower RI limit obtained using the Q-Q plot and nonparametric test). The Hoffmann and Bhattacharya methods may provide reliable RIs for indirect estimations of urea, creatinine, and UA based on laboratory datasets.