血清骨代谢标志物实验室检测基于生物学变异的允许总误差在可比性验证中的应用

目的 通过分析血清骨代谢标志物实验室检测项目基于生物学变异的允许总误差(total error,TEa)质量指标与基于室间质量评价(external quality assessment, EQA)TEa 质量指标在实验室可比性验证中的结果，评价基于生物学变异的TEa 质量指标在血清骨代谢标志物室内、外可比性验证中的实用性。方法 收集宝鸡市中心医院2021 年11~12 月血清骨代谢标志物试剂更换批次可比性验证数据，同时收集相同项目2021 年第2 次实验室间比对数据，计算相对偏差。项目包括骨钙素、总Ι 型胶原氨基端延长肽(TP1NP)、β- 胶原特殊序列(β-CTX)、甲状旁腺素(PTH)和25-羟维生素D3[D3(25-OH)]。通过王治国主编《临床检验生物学变异与参考区间》附录获取血清骨代谢标志物基于生物学变异的TEa 质量指标，以国家卫生健康委临床检验中心2021 年第2 次EQA 反馈报告，获取EQA 的TEa 质量指标，将可比性验证数据用此两种来源质量指标做符合要求率判断，以P ＜ 0.05 为差异有统计学意义。结果 以基于EQA 或专家推荐的TEa 为质量标准，血清骨代谢标志物试剂更换批号、室间比对的5 个项目的符合要求率均为100% , 可比性验证全部通过。以基于生物学变异TEa 的最低质量标准判断，试剂更换批号、室间比对符合要求率80%~100% , 两种来源判断标准结果比较符合要求率的差异无统计学意义(χ2 ≥ 1.000，均P ＞ 0.05), 可比性验证通过。以基于生物学变异TEa 适当质量标准判断，则5 个项目符合要求率为20%~100%，β-CTX，骨钙素试剂更换批号比对符合要求率分别为20% 和40%，差异有统计学意义(χ2=0.048，0.246，均P ＜ 0.05), 可比性验证不能通过；此时室间比对的符合要求率60%-100%，差异无统计学意义(χ2=0.444~1.000，均P ＞ 0.05)，但符合率60% 的β-CTX 可比性验证不能通过。结论 血清骨代谢标志物实验室检测基于生物学变异的TEa 质量指标可以通过生物学变异数据库获得[D3(25-OH) 除外]，有3 级性能指标，更科学、更严谨，建议实验室首选应用。

Application of Allowable Total Error Based on Biological Variation in Comparability Verification of Serum Bone Metabolism Markers in Laboratory Detection

Objective To verify the comparability between the total error (TEa) quality index based on biological variation and the TEa quality index based on external quality assessment (EQA) in the laboratory testing items of serum bone metabolism markers. The results in this study were used to evaluate the utility of biological variation-based TEa quality indicators in the validation of serum bone metabolism markers in vitro and in vivo comparability. Methods The comparability verification data of replacement batches of serum bone metabolism marker reagents in Baoji Central Hospital from November to December 2021 were collected, and the second inter-laboratory comparison data of the same project in 2021 was collected to calculate the relative deviation. Items include osteocalcin, total collagen type 1 amino-terminal extension peptide (TP1NP), β-collagen specific sequence (β-CTX), parathyroid hormone (PTH) and 25-hydroxyvitamin D3 [D3(25-OH)] . Obtain the TEa quality index of serum bone metabolism markers based on biological variation through the appendix of Clinical Testing Biological Variation and Reference Interval edited by WANG Zhiguo, and obtain the TEa quality index of EQA based on the second EQA feedback report of the National Center for Clinical Laboratory in 2021. The comparability verification data were judged by these two source quality indicators as the compliance rate, and P < 0.05 was considered to be statistically significant. Results With the quality standard based on EQA or TEa recommended by experts, the compliance rates of the five items of serum bone metabolism marker reagent replacement batch number and inter-laboratory comparison were all 100%, and the comparisons were all passed. Judging by the minimum quality standard based on biological variation TEa, the compliance rate of reagent replacement batch number and inter-laboratory comparison was 80%~100%, and the difference in compliance rate between the two source judgment standards was not statistically significant (χ2 ≥ 1.000, all P > 0.05), the comparison was passed. Judging by the appropriate quality standard based on biological variation TEa, the compliance rate of 5 items was 20%~100%, and the compliance rates of β-CTX and osteocalcin reagent replacement batch numbers were 20% and 40%, respectively, with the differences were statistically significant (χ2 = 0.048, 0.246, all P < 0.05), the comparison failed. The compliance rate of the inter-laboratory comparison was 60%~100%, and the differences were not statistically significant (χ2 = 0.444~1.000, all P > 0.05), but the β-CTX alignment with a coincidence rate of 60% could not pass. Conclusion The TEa quality indicators based on biological variation in the laboratory detection of serum bone metabolism markers could be obtained through the biological variation database [except D3(25-OH)]. There are three-level performance indicators, which are more scientific and more rigorous. Recommended laboratory preferred application.