Weiss Nathalie, Vierbaum Laura, Kremser Marcel, Kaufmann-Stoeck Anne, Kappler Silke, Ballert Silvia, Kabrodt Kathrin, Hunfeld Klaus-Peter, Schellenberg Ingo
INSTAND e.V., Society for Promoting Quality Assurance in Medical Laboratories e.V., Duesseldorf, Germany.
Institute of Bioanalytical Sciences (IBAS), Center of Life Sciences, Anhalt University of Applied Sciences, Bernburg, Germany.
Front Mol Biosci. 2024 Aug 8;11:1401405. doi: 10.3389/fmolb.2024.1401405. eCollection 2024.
C-reactive protein (CRP) is an established serum biomarker for different pathologies such as tissue injury and inflammatory events. One rising area of interest is the incorporation of low concentrations of CRP, so called high-sensitive (hs-) CRP, in the risk assessment and treatment monitoring of cardiovascular diseases (CVDs). Many research projects and the resulting meta-analyses have reported controversial results for the use of hs-CRP, especially in the risk assessment of CVDs. However, since these analyses used different assays to detect hs-CRP, it is important to assess the current level of assay harmonization.
This paper analyzes data from 17 external quality assessment (EQA) surveys for hs-CRP conducted worldwide between 2018 and 2023. Each EQA survey consisted of two blinded samples. In 2020 the sample material changed from pooled serum to single-donor samples. The aim was to assess the current status of assay harmonization by a manufacturer-based approach, taking into consideration the clinical decision limits for hs-CRP risk-stratification of CVDs as well as the scatter of results.
Our analyses show that harmonization has increased in recent years from median differences of up to 50% to below 20%, with one exception that showed an increasing bias throughout the observed period. After changing sample materials from pools to single-donor samples, the coefficient of variation decreased to below 10% with one exception. Nevertheless, even these differences in the clinical setting could lead to disparate classification of patients depending on the assay used.
While there was a positive trend towards harmonization, meta-analysis of different risk-score publications should stratify their analysis by assay to account for the manufacturer-specific differences observed in this paper. Furthermore, assays are currently traceable to different international standard preparations, which might have a negative impact on future harmonization.
C反应蛋白（CRP）是一种既定的血清生物标志物，用于检测不同的病理状况，如组织损伤和炎症事件。一个日益受到关注的领域是将低浓度的CRP，即所谓的高敏（hs-）CRP，纳入心血管疾病（CVD）的风险评估和治疗监测中。许多研究项目以及由此产生的荟萃分析报告了使用hs-CRP的争议性结果，特别是在CVD的风险评估方面。然而，由于这些分析使用了不同的检测方法来检测hs-CRP，评估当前检测方法的一致性水平很重要。
本文分析了2018年至2023年期间在全球范围内进行的17次hs-CRP外部质量评估（EQA）调查的数据。每次EQA调查包括两个盲样。2020年，样本材料从混合血清改为单供体样本。目的是通过基于制造商的方法评估当前检测方法的一致性状态，同时考虑到CVD风险分层的hs-CRP临床决策限以及结果的离散度。
我们的分析表明，近年来一致性有所提高，中位数差异从高达50%降至20%以下，但有一个例外，在整个观察期内偏差呈上升趋势。将样本材料从混合样本改为单供体样本后，变异系数降至10%以下，但有一个例外。然而，即使在临床环境中的这些差异也可能导致根据所使用的检测方法对患者进行不同的分类。
虽然存在朝着一致性发展的积极趋势，但对不同风险评分出版物的荟萃分析应按检测方法对其分析进行分层，以考虑本文中观察到的制造商特定差异。此外，目前不同的检测方法可追溯到不同的国际标准制剂，这可能对未来的一致性产生负面影响。
