National Centre for Epidemiology and Population Health, The Australian National University, Canberra, Australian Capital Territory, Australia.
Intern Med J. 2012 Jan;42(1):43-50. doi: 10.1111/j.1445-5994.2011.02471.x.
Measuring serum 25(OH)D concentration is common in clinical practice despite the questionable reliability of assays.
The aim of the present study was to examine agreement in 25(OH)D concentrations measured by different assays and laboratories, and consider related clinical implications.
Serum samples from 813 participants in the Australian Multicentre Study of Environment and Immune Function (the Ausimmune Study) were assayed for 25(OH)D concentration. Duplicate samples from subsets of subjects were sent to different laboratories, two using DiaSorin Liaison (Laboratory A and B) and one using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS - selected here as the nominal gold standard). Pairwise within-assay (both within-laboratory and between-laboratories) and between-assay agreement was examined using Deming regression and Bland-Altman plots. Common 25(OH)D cut-points for classification of vitamin D deficiency were used to compare the different assays.
25(OH)D concentrations measured using Liaison were substantially lower at Laboratory A than at Laboratory B (mean bias -11.60 nmol/L, 95% limits of agreement -46.39, 23.18). Both Liaison assays returned much lower 25(OH)D concentrations than LC-MS/MS (mean bias up to -26.05 nmol/L, 95% limits of agreement of -13.21, 65.31). For Laboratory A participants, 46% (355/765) were classified as vitamin D deficient (25(OH)D <50 nmol/L) using Liaison compared with 17% (128/765) using LC-MS/MS. For Laboratory B participants, the respective figures were 36% (76/209) and 20% (41/209). Hence, between 1-in-5 and 1-in-3 participants were misclassified as 'deficient'.
Bias and variability in 25(OH)D measurements sufficient to affect significantly clinical decision-making were found both between-laboratories and between-assays. The adoption of common standards to allow assay calibration is required urgently.
尽管检测方法的可靠性存在疑问，但测量血清 25（OH）D 浓度在临床实践中很常见。
本研究旨在检查不同检测方法和实验室测量的 25（OH）D 浓度的一致性，并考虑相关的临床意义。
对澳大利亚环境与免疫功能多中心研究（Ausimmune 研究）中的 813 名参与者的血清样本进行 25（OH）D 浓度检测。从部分受试者中发送了重复样本到不同的实验室，其中两个使用 DiaSorin Liaison（实验室 A 和 B），一个使用液相色谱-串联质谱法（LC-MS/MS- 这里选择作为名义金标准）。使用 Deming 回归和 Bland-Altman 图检查了实验室内（包括实验室内和实验室间）和实验室间的检测内和检测间的一致性。使用常见的 25（OH）D 截断值来比较不同的检测方法，以对维生素 D 缺乏症进行分类。
与实验室 B 相比，Liaison 在实验室 A 测量的 25（OH）D 浓度明显较低（平均偏差-11.60nmol/L，95%置信区间-46.39，23.18）。两种 Liaison 检测方法返回的 25（OH）D 浓度均低于 LC-MS/MS（最大平均偏差-26.05nmol/L，95%置信区间-13.21，65.31）。对于实验室 A 的参与者，使用 Liaison 时，46%（355/765）被归类为维生素 D 缺乏症（25（OH）D <50nmol/L），而使用 LC-MS/MS 时为 17%（128/765）。对于实验室 B 的参与者，相应的数字分别为 36%（76/209）和 20%（41/209）。因此，每 5 到 3 名参与者中就有 1 到 1 名被错误归类为“缺乏”。
在实验室间和实验室间均发现 25（OH）D 测量的偏差和变异性足以显著影响临床决策。迫切需要采用共同的标准来实现检测校准。
