De Grande Linde A C, Van Uytfanghe Katleen, Reynders Dries, Das Barnali, Faix James D, MacKenzie Finlay, Decallonne Brigitte, Hishinuma Akira, Lapauw Bruno, Taelman Paul, Van Crombrugge Paul, Van den Bruel Annick, Velkeniers Brigitte, Williams Paul, Thienpont Linda M
Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
Ref4U, Laboratory of Toxicology, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
Clin Chem. 2017 Oct;63(10):1642-1652. doi: 10.1373/clinchem.2017.274407. Epub 2017 Jul 18.
The IFCC Committee for Standardization of Thyroid Function Tests intended to standardize free thyroxine (FT) immunoassays. We developed a Système International d'Unités traceable conventional reference measurement procedure (RMP) based on equilibrium dialysis and mass spectrometry. We describe here the latest studies intended to recalibrate against the RMP and supply a proof of concept, which should allow continued standardization efforts.
We used the RMP to target the standardization and reference interval (RI) panels, which were also measured by 13 manufacturers. We validated the suitability of the recalibrated results to meet specifications for bias (3.3%) and total error (8.0%) determined from biological variation. However, because these specifications were stringent, we expanded them to 10% and 13%, respectively. The results for the RI panel were reported as if the assays were recalibrated. We estimated all but 1 RI using parametric statistical procedures and hypothesized that the RI determined by the RMP was suitable for use by the recalibrated assays.
Twelve of 13 recalibrated assays had a bias, meeting the 10% specification with 95% confidence; for 7 assays, this applied even for the 3.3% specification. Only 1 assay met the 13% total error specification. Recalibration reduced the CV of the assay means for the standardization panel from 13% to 5%. The proof-of-concept study confirmed our hypothesis regarding the RI but within constraints.
Recalibration to the RMP significantly reduced the FT immunoassays' bias, so that the RI determined by the RMP was suitable for common use within a margin of 12.5%.
国际临床化学和检验医学联合会（IFCC）甲状腺功能检测标准化委员会旨在规范游离甲状腺素（FT）免疫测定。我们基于平衡透析和质谱法开发了一种可溯源至国际单位制（SI）的传统参考测量程序（RMP）。我们在此描述旨在根据RMP进行重新校准并提供概念验证的最新研究，这应有助于持续的标准化工作。
我们使用RMP对标准化和参考区间（RI）样本组进行校准，13家制造商也对这些样本组进行了测量。我们验证了重新校准结果是否符合根据生物学变异确定的偏差（3.3%）和总误差（8.0%）规范。然而，由于这些规范较为严格，我们分别将其扩大到10%和13%。RI样本组的结果报告方式就如同各检测方法已经重新校准一样。我们使用参数统计程序估计了除1个之外的所有RI，并假设由RMP确定的RI适用于重新校准后的检测方法。
13种重新校准的检测方法中有12种存在偏差，在95%置信度下符合10%的规范；对于7种检测方法，即使是3.3%的规范也适用。只有1种检测方法符合13%的总误差规范。重新校准使标准化样本组检测均值的变异系数从13%降至5%。概念验证研究证实了我们关于RI的假设，但存在一定限制。
根据RMP进行重新校准显著降低了FT免疫测定的偏差，因此由RMP确定的RI在12.5%的范围内适用于常规使用。
