CLOSING THE LOOP – APPLYING REFERENCE MEASUREMENT SERVICES TO EXTERNAL QUALITY ASSURANCE FOR ROUTINE CLINICAL CHEMISTRY TESTS

Abstract

Introduction Low between-method bias is vital for interpretation of medical laboratory tests for patient care. For common clinical chemistry tests the manufacturers are responsible for providing reagents, instruments and calibrators which can provide traceable results. The Royal College of Pathologists of Australasia Quality Assurance Program (RCPAQAP) has run an external quality assurance program with presumed commutable materials – The Liquid Serum Chemistry Program - for over 10 years. Currently over 270 laboratories are enrolled measuring up to 60 measurands with 2 or 4 samples per year. In 2022 and 2023 two samples each year were sent for value assignment in JCTLM-listed Reference Measurement Services (RMS). We assess the added utility of performing this RMS testing. Methods Freshly collected serum samples are frozen and rapidly distributed. Laboratories submit results to the RCPAQAP together with supporting information including instrument, reagent manufacturer and method principle. Samples were also sent to either RFB in Germany or WEQAS in Wales for RMS testing for 14 measurands. The following instrument groups were assessed: Abbott Alinity and Architect, Beckman-Coulter AU, QuidelOrtho Vitros, Roche Cobas, and Siemens Atellica and Dimension. Bias assessment was made against the overall method median and against RMS values, using criteria based on Australian common reference intervals, biological variation or expert recommendations. Results The effect of performing the RMS testing added to result interpretation in the following ways. For some tests with acceptable between-method bias for all methods, it was shown that all methods were also unbiased to the RMS results (ALT(+P5P), ALP, creatinine, urate). For tests where one or more method was biased relative to the all-assay median, that most methods had acceptable bias and the outlier method(s) were biased against the RMS result (AST(+P5P) – Dimension low; CK – Vitros low; Cholesterol – Beckman high; Amylase – Dimension low; Calcium – Dimension low; Magnesium – Atellica Low; Triglycerides – Vitros, Roche High). For GGT and Glucose all methods showed a bias to the RMS (negative and positive respectively). For ALP, LDH and cholesterol there was a change in the bias for all methods relative to the RMS between 2022 and 2023. For ALP all methods remained within acceptable bias, but for LDH, while between-method bias was acceptable, for 2022 data several methods exceeded bias limits against the RMS. These inconsistent biases, or all-method biases raise concerns about analyte stability and sample handling for RMS testing which is generally delayed and further afield. Discussion Reference method value assignment for presumed commutable EQA samples can increase confidence that methods working correctly, and can support identification of poorly performing methods. The Measurement Uncertainty of RMS results can be relevant in assessing method bias. Limitations to providing RMS testing include sample stability; required sample volumes; the limited number samples included; and costs. We note that in this study we included only 14 of the measurands in the program. Conclusions Correctly performed RMS testing of commutable EQA materials adds supporting information that manufacturers are supplying traceable assays, and supplies evidence for methods that may need improvement.