Abstract：
OBJECTIVE: Harmonization has been recommended by the International Organization for Standard (ISO) to achieve equivalent results across in vitro diagnostic measurement devices (IVD-MDs). We aim to evaluate the effectiveness of Bland-Altman plot-based harmonization algorithm (BA-BHA) created in this study and compare it with weighted Deming regression-based harmonization algorithm (WD-BHA) proposed in ISO 21151:2020.
METHODS: Eighty patient sera were used as the harmonization reference material (HRM) to develop IVD-MD-specific harmonization algorithms. Another panel of 40 patient sera was used to validate the effectiveness of harmonization algorithms. We compared regression slopes, intercepts, Bland-Altman plot layouts, percent differences, limits of agreement (LoAs), between-method coefficients of variation (CV) before and after harmonization.
RESULTS: After harmonization by WD-BHA, acceptable slopes and intercepts between measured values and HRM targets were observed in weighted Deming regression, but not in Passing-Bablok analysis. Mean differences were -5.5 to 5.0 % and differences at specific levels were -33.9 to 23.9 %. LoAs were -64.6 to 74.6 %. Between-method CV was 22.9 % (±12.9 %). However, after harmonization by BA-BHA, both weighted Deming and Passing-Bablok regressions equations presented harmonized results. Mean differences were -0.3 to 0.2 % and differences at specific levels were -1.1 to 1.6 %. LoAs were -23.3 to 23.2 %. Between-method CV was 8.4 % (±4.0 %). The data points were evenly distributed at both sides of the mean in Bland-Altman plots.
CONCLUSIONS: The inequivalence of test results between different methods can be improved but unacceptable analytical differences at specific levels may be hidden in terms of an acceptable slope and intercept on WD-BHA. The new protocol BA-BHA may be a viable alternative to optimize the harmonization for immunoassays.
METHODS: Eighty patient sera were used as the harmonization reference material (HRM) to develop IVD-MD-specific harmonization algorithms. Another panel of 40 patient sera was used to validate the effectiveness of harmonization algorithms. We compared regression slopes, intercepts, Bland-Altman plot layouts, percent differences, limits of agreement (LoAs), between-method coefficients of variation (CV) before and after harmonization.
RESULTS: After harmonization by WD-BHA, acceptable slopes and intercepts between measured values and HRM targets were observed in weighted Deming regression, but not in Passing-Bablok analysis. Mean differences were -5.5 to 5.0 % and differences at specific levels were -33.9 to 23.9 %. LoAs were -64.6 to 74.6 %. Between-method CV was 22.9 % (±12.9 %). However, after harmonization by BA-BHA, both weighted Deming and Passing-Bablok regressions equations presented harmonized results. Mean differences were -0.3 to 0.2 % and differences at specific levels were -1.1 to 1.6 %. LoAs were -23.3 to 23.2 %. Between-method CV was 8.4 % (±4.0 %). The data points were evenly distributed at both sides of the mean in Bland-Altman plots.
CONCLUSIONS: The inequivalence of test results between different methods can be improved but unacceptable analytical differences at specific levels may be hidden in terms of an acceptable slope and intercept on WD-BHA. The new protocol BA-BHA may be a viable alternative to optimize the harmonization for immunoassays.
摘要：
目的：国际标准组织（ISO）建议进行协调，以在体外诊断测量设备（IVD-MD）中获得等效结果。我们旨在评估本研究中创建的Bland-Altman基于图的协调算法（BA-BHA）的有效性，并将其与ISO21151：2020中提出的基于加权Deming回归的协调算法（WD-BHA）进行比较。
方法：使用80例患者血清作为协调参考材料（HRM）来开发IVD-MD特异性协调算法。另一组40名患者血清用于验证协调算法的有效性。我们比较了回归斜率，拦截,Bland-Altman地块布局,百分比差异，协议限制(LoAs)，协调前后的方法间变异系数(CV)。
结果：经过WD-BHA的协调，在加权戴明回归中观察到测量值和人力资源管理目标之间的可接受斜率和截距，但不是在Passing-Bablok分析中。平均差异为-5.5至5.0％，特定水平的差异为-33.9至23.9％。LoAs为-64.6％至74.6％。方法间CV为22.9%(±12.9%)。然而,经BA-BHA协调后，加权Deming和Passing-Bablok回归方程都给出了协调的结果。平均差异为-0.3至0.2％，特定水平的差异为-1.1至1.6％。LoAs为-23.3至23.2%。方法间CV为8.4%(±4.0%)。在Bland-Altman图中，数据点平均分布在平均值的两侧。
结论：可以改善不同方法之间的测试结果的不等效性，但就WD-BHA的可接受斜率和截距而言，特定水平的不可接受的分析差异可能被隐藏。新方案BA-BHA可能是优化免疫测定协调的可行替代方案。
方法：使用80例患者血清作为协调参考材料（HRM）来开发IVD-MD特异性协调算法。另一组40名患者血清用于验证协调算法的有效性。我们比较了回归斜率，拦截,Bland-Altman地块布局,百分比差异，协议限制(LoAs)，协调前后的方法间变异系数(CV)。
结果：经过WD-BHA的协调，在加权戴明回归中观察到测量值和人力资源管理目标之间的可接受斜率和截距，但不是在Passing-Bablok分析中。平均差异为-5.5至5.0％，特定水平的差异为-33.9至23.9％。LoAs为-64.6％至74.6％。方法间CV为22.9%(±12.9%)。然而,经BA-BHA协调后，加权Deming和Passing-Bablok回归方程都给出了协调的结果。平均差异为-0.3至0.2％，特定水平的差异为-1.1至1.6％。LoAs为-23.3至23.2%。方法间CV为8.4%(±4.0%)。在Bland-Altman图中，数据点平均分布在平均值的两侧。
结论：可以改善不同方法之间的测试结果的不等效性，但就WD-BHA的可接受斜率和截距而言，特定水平的不可接受的分析差异可能被隐藏。新方案BA-BHA可能是优化免疫测定协调的可行替代方案。
