Laboratory standardization of a large international clinical trial: The DAIS experience

Objective: To implement a duality control program for the standardization a nd harmonization of lipid and lipoprotein analyses as performed at two core laboratories (St. Paul's Hospital, UBC [Vancouver], and NPHI [Helsinki]) f or the Diabetes Atherosclerosis Intervention Study (DAIS). Design and methods: A DAISSOFT computer program was designed to minimize th e occurrence of data and sample management errors during the course of the study. Fresh human serum was used for the provision of an accuracy based ex ternal quality control program that monitored the analytical performance of lipid testing at these two laboratories. A separate program was designed f or monitoring hemoglobin A(1c) (HbA(1c)). At the outset of the study, allow able total error goals were established for each analyte. Ongoing performan ce was monitored using bimonthly blinded challenges of fresh human serum. T he two EQA programs routinely monitored the analysis of total cholesterol, calculated LDL-cholesterol, HDL-cholesterol, net triglycerides, apoprotein A-1, apoprotein B, and HbA(1c). Results: The EQA precision and accuracy data for the measurement of total c holesterol at the two core laboratories over the last 5 years indicated bot h laboratories operated with good precision, approximately 1% CV over the t ime period. The accuracy at both laboratories was similar initially. Part w ay through the study, the accuracy of the cholesterol method at NHPI tended to drift upward with an operating positive bias (+3%) relative to the Abel l Kendall reference method. Triglyceride measurements were the most problem atic for the study. By EQA cycle 8, the accuracy of the method at UBC had s tabilized and was meeting the accuracy goals of the study. NPHI's method wa s negatively biased relative to the accuracy base of the DAIS study. In spi te of recalibrating their method, NPHI found it difficult to maintain consi stent accuracy for the measurement of triglycerides during the study. Both laboratories operated their HDL methods with excellent precision. Accuracy at NHPI was well maintained over the course of the study whereas the accura cy of HDL measurements at UBC was more problematic. There was an inconsiste nt variation in the accuracy of apoprotein A-1 measurements at both laborat ories. In most cases, the bias would be corrected by the time of the next E QA challenge. In the case of apo B, one laboratory was standardized to the CDC while the other laboratory was standardized to IFCC/WHO. The discrepanc y between these two accuracy bases was > 20%. Recalibration to a common acc uracy base rectified the problem. Only minor problems were encountered with the precision and accuracy of the DIAMAT assay for hemoglobin A-1c. The tw o DAIS core laboratories consistently operated within the 9% total error go als of the study for HbA(1c). Conclusions: Through the use of this program, the two DAIS core laboratorie s were able to maintain their lipid analyses within the limits of allowable total error that had been established for the study. Copyright (C) 2000 Th e Canadian Society of Clinical Chemists.