Using Bland-Altman plot-based harmonization algorithm to optimize the harmonization for immunoassays

Huiling Fang; Ruifeng Yang; Jiayue Guo; Xinxin Ren; Xin Chang; Lan Kang; Yuqing Zhu

doi:10.1515/cclm-2024-0187

Article

Using Bland-Altman plot-based harmonization algorithm to optimize the harmonization for immunoassays

Huiling Fang , Ruifeng Yang , Jiayue Guo , Xinxin Ren , Xin Chang , Lan Kang and Yuqing Zhu

Published/Copyright: May 15, 2024

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From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 62 Issue 11

Abstract

Objectives

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.

Keywords: harmonization; Bland-Altman plot; weighted Deming regression; harmonization reference material

Corresponding author: Yuqing Zhu, Department of Clinical Chemistry and Immunology, Shanghai Center for Clinical Laboratory, Shanghai 200126, P.R. China, E-mail: zhuyuqing@sccl.org.cn

Huiling Fang and Ruifeng Yang contributed equally to this work.

Research ethics: Research involving human subjects complied with all relevant national regulation, institutional policies and is in accordance with the tenets of the Helsinki Declaration (as revised in 2013), and has been approved by Ethics Committee of Peking University People’s Hospital (PKUPH-2023-090).
Informed consent: Not applicable.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: The authors state no conflict of interest.
Research funding: None declared.
Data availability: The raw data can be obtained on request from the corresponding author.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2024-0187).

Received: 2023-09-15

Accepted: 2024-04-30

Published Online: 2024-05-15

Published in Print: 2024-10-28

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https://doi.org/10.1515/cclm-2024-0187

Keywords for this article

harmonization; Bland-Altman plot; weighted Deming regression; harmonization reference material