Department of Clinical Chemistry, St. Olav's Hospital, Trondheim, Norway.
Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
Clin Chem Lab Med. 2023 Jun 28;61(12):2212-2215. doi: 10.1515/cclm-2023-0478. Print 2023 Nov 27.
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.
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.
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.
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.
当患者分析物的平均（设定点）浓度未知，且医生试图根据相隔一段时间采集的两个单独样本中的分析物浓度来判断临床情况时，我们认为应该使用来自临床健康且稳定个体的双变量参考区间来判断这两个值，而不是使用单变量参考限值并比较值与参考变化值（RCV）之间的差异。在这项工作中，我们使用 s-TSH 作为示例比较了这两种模型。
我们模拟了 100000 名甲状腺功能正常受试者的两个 s-TSH 测量值，并将第二个值与第一个值进行比较，同时标记出双变量分布的中心 50%、60%、70%、80%、90%和 95%，以及单变量参考限值的 2.5%和 97.5%分位数和 RCV 的 2.5%和 97.5%分位数。我们还估计了 2.5%和 97.5%单变量参考限值分位数和 2.5%和 97.5%RCV 与双变量分布中心 95%的组合对诊断准确性的影响。
图形上，2.5%和 97.5%单变量参考限值与 2.5%和 97.5%RCV 的组合不能准确划定双变量分布的中心 95%。数值上，该组合的敏感性和特异性分别为 80.2%和 92.2%。
从临床健康且稳定的个体中两次分别采集的 s-TSH 样本的浓度不能使用单变量参考限值和 RCV 的组合进行准确解释。
