Improving the performance of biochemical genetic testing through external quality assessment

OBJECTIVES: External quality assessment (EQA) is essential for ensuring reliable biochemical genetic testing. This study evaluated long-term performance trends in ERNDIM quantitative EQA schemes, including special assays in serum (SAS), special assays in urine (SAU), purines and pyrimidines in urine (PPU), quantitative organic acids in urine (QTOU), quantitative amino acids in serum (QTAS), acylcarnitines in serum (ACS), and special assays in dried blood spots (SADB). METHODS: Longitudinal trends in between- and within-laboratory coefficient of variation (CV) and their ratios as indicators of harmonisation were evaluated using ERNDIM EQA annual report data from 2000 to 2024. RESULTS: Means of between- and within-laboratory CVs differed substantially across schemes. In 2024, between- respective within-laboratory CVs (%) were: QTAS 10;6, SAS 12;7, SAU 14;7, PPU 14;8, ACS 25;10; SABD 26;10, and QTOU 36;17. Marked variability was also observed across individual analytes, particularly for low-concentration metabolites, compounds with specific functional groups, and those analysed without isotopically labelled internal standards. Improvements in CVs were mainly seen in the early years of EQA scheme implementation. No longitudinal trend was observed for QTAS, which consistently showed the best performance. CONCLUSIONS: The marked variation in performance between schemes and analytes may be linked to differences in analytical methodology, analyte properties, availability of commercial reference materials, sample matrix, and experience. Overall, ERNDIM quantitative schemes effectively monitor performance, support harmonisation, and provide educational feedback.