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

Clinical chemistry laboratory results from different laboratories often sho w large between-laboratory variation due to factors such as differences in method principles, method applications, calibration procedures or the appli cation of different instrument factor settings within the same calibration procedure. We have examined the possible use of common calibrators to reduc e this variation. Three different calibrators were compared: A, freeze-drie d preparations of pooled patients' serum samples, spiked to give three conc entration levels; B, freeze-dried preparations of pooled patients' serum sa mples selected on the basis of elevated enzyme activities at three levels: C, a single calibrator consisting of frozen pooled serum samples. These cal ibrators were sent to 11 participating laboratories together with 14 fresh patients' serum samples. We report the variation of the results of 21 gener al clinical chemistry analytes obtained in the patients' serum samples befo re 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 f rom more than 30% (enzymes) to values well within the bias limits set by Eu ropean quality specifications, when the necessary conditions are met. These conditions include the commutability of the calibrator(s) with fresh patie nts' material. For the enzymes, calibrator material originating from select ively pooled patients' samples appeared to be necessary, whereas for the su bstrates selectively pooled serum calibrators spiked with exogenous supplem ents may be used. For harmonization to be effective in practice, calibrator s need to be stable over time and to carry assigned values set by certified reference laboratories, and the quality performance of participating labor atories should be appropriately monitored.