A model for harmonization of routine clinical chemistry results between clinical laboratories

Abstract

SUMMARY. Clinical chemistry laboratory results from different laboratories often show large between-laboratory variation due to factors such as differences in method principles, method applications, calibration procedures or the application of different instrument factor settings within the same calibration procedure. We have examined the possible use of common calibrators to reduce this variation. Three different calibrators were compared: A, freeze-dried preparations of pooled patients' serum samples, spiked to give three concentration levels; B, freeze-dried preparations of pooled patients' serum samples selected on the basis of elevated enzyme activities at three levels; C, a single calibrator consisting of frozen pooled serum samples. These calibrators were sent to 11 participating laboratories together with 14 fresh patients' serum samples. We report the variation of the results of 21 general clinical chemistry analytes obtained in the patients' serum samples before and after recalculation on the basis of the results of the calibrators. For most analytes the use of a multiple point linear regression calibration function is able to reduce the between-laboratory variation considerably from more than 30% (enzymes) to values well within the bias limits set by European quality speci®cations, when the necessary conditions are met. These conditions include the commutability of the calibrator(s) with fresh patients' material. For the enzymes, calibrator material originating from selectively pooled patients' samples appeared to be necessary, whereas for the substrates selectively pooled serum calibrators spiked with exogenous supplements may be used. For harmonization to be effective in practice, calibrators need to be stable over time and to carry assigned values set by certi®ed reference laboratories, and the quality performance of participating laboratories should be appropriately monitored.

Commutability of Calibration and Control Materials for Serum Lipase

“…The examples given here show that the recalibration with commutable CCMs may permit a correction of the original intermethod differences (Table 3), as already shown for other components (13,14,23,24 ). Two-point recalibration more effectively corrected the constant component of intermethod differences.…”

“…Nonetheless, one approach to standardizing enzyme activity assays is to calibrate routine methods with CCMs that have values assigned by a "comparison" method (22 ). For such a procedure to be effective, the CCMs must be commutable (23 ). Consistent with its definition (9 ), commutability of CCMs with patient sera, in a stated pair of methods, is considered here as a "relative" property, comparing the intermethod behavior of each CCM with the population of patient sera, whichever dispersion the latter may show.…”

Neonatal Intrahepatic Cholestasis Caused by Citrin Deficiency Differentiated from Biliary Atresia

“…These methods often experience interference by metabolites such as galactose and by enzymes relating to the assay reaction. 24 HPLC separation of hexose isomers, such as glucose, galactose, and fructose, is complicated and time consuming. Here, the separation was omitted, demonstrating the feasibility of this technique to acquire reasonable measurements of total hexose concentrations for the screening and diagnosis of hypoglycemia or hyperglycemia, as reported previously.…”

Application of five frozen human-pooled serum samples assigned by the International Federation of Clinical Chemistry and Laboratory Medicine reference procedure in a traceability investigation of γ-glutamyltransferase catalytic concentration measurements in China

“…using correction functions in the case of homogeneous linear regression analysis, normal linear regression analysis and one-point calibration. Baadenhuijsen et al 20 suggested that the reduction in variation was not related to the type of correction function and that a sensible choice of calibrator concentration for one-point calibration was feasible. In our study most systems indicated a high bias when samples at level one and two were measured.…”