Objectives: When the patient's mean (setpoint) concentration of an analyte is unknown and the physician tries to judge the clinical condition from the analyte concentration in two separate specimens taken a time apart, we believe that the two values should be judged against a bivariate reference interval derived from clinically healthy and stable individuals, rather than using univariate reference limits and comparing the difference between the values against reference change values (RCVs). In this work we compared the two models, using s-TSH as an example.
Methods: We simulated two s-TSH measurement values for 100,000 euthyreot subjects, and plotted the second value against the first, along with a markup of the central 50, 60, 70, 80, 90, and 95 % of the bivariate distribution, in addition to the 2.5 and 97.5 percentile univariate reference limits and the 2.5 and 97.5 percentile RCVs. We also estimated the diagnostic accuracy of the combination of the 2.5 and 97.5 univariate percentile reference limits and the 2.5 and 97.5 percentile RCVs against the central 95 % of the bivariate distribution.
Results: Graphically, the combination of the 2.5 and 97.5 univariate reference limits and the 2.5 and 97.5 percentile RCVs did not accurately delineate the central 95 % of the bivariate distribution. Numerically, the sensitivity and specificity of the combination were 80.2 and 92.2 %, respectively.
Conclusions: The concentrations of s-TSH measured in two samples taken at separate times from a clinically healthy and stable individual cannot be accurately interpreted using the combination of univariate reference limits and RCVs.
Keywords: biological variation; bivariate distribution; reference change values; within-subject variation.
© 2023 the author(s), published by De Gruyter, Berlin/Boston.