BACKGROUND:Assuring/demonstrating metrologic traceability of in vitro diagnostics necessitates the availability of measurand-specific reference measurement systems (RMSs) and the possibility for industry to work with competent reference measurement laboratories (RMLs). Here we report the results of a European project to investigate the feasibility of developing a RMS for serum total thyroxine.METHODS:Four candidate RMLs (cRMLs) developed/implemented variants of a candidate reference measurement procedure (cRMP) based on isotope dilution-liquid chromatography-mass spectrometry. The sole constraint implemented was calibration with a common thyroxine primary calibrator. The RMPs were externally validated and assessed for comparability in round-robin trials using common samples, i.e., 5 lyophilized and 33 frozen native sera. At the same time, the performance of the cRMLs organized in a network was assessed. For uniform external quality assessment, common performance specifications were agreed on.RESULTS:All cRMLs performed the cRMPs with fulfillment of the predefined specifications: total and between-laboratory CVs < or =2.0% and 2.5%, respectively, and a systematic deviation < or =0.9%, estimated with a target assigned from the mean of means obtained by the cRMLs. The mean expanded uncertainty for value assignment to the native sera was 2.1%.CONCLUSIONS:A network of cRMLs, with externally conformed competence to properly perform RMPs, has been established. Performance specifications were defined and will form the basis for admittance of new network members. A serum panel, successfully targeted during the validation process, is available for split-sample measurements with commercial routine measurement procedures. The model can now be used for other measurands for which traceability to the Systeme International d'Unites is needed.

Background: Diagnostic manufacturers* must ensure/ document metrologically traceable assays. We report on a feasibility study of a split-sample comparison for that purpose. Processed, frozen single-donation sera, assigned target values by candidate reference measurement procedures (cRMPs), were used with immunoassays for total thyroxine (TT4) and triiodothyronine (TT3) as models.Methods: Two serum panels were quantified for TT3 and TT4 with validated cRMPs and measured in parallel with at least 14 immunoassays. The results were interpreted in terms of traceability of calibration (trueness) and of the individual measurement result (accuracy) by linear regression analysis and graphical representation against specifications. The commutability of the sera was investigated by parallel analysis of TT4 in freshly collected but nonfiltered specimens.Results: The TT4 (TT3) concentrations in the sera (according to the cRMPs) were 64-269 nmol/L (0.88-13.7 nmol/L). The method comparison showed that for TT4 on average, the immunoassays produced results in agreement with the cRMPs, whereas for TT3, results were typically higher. It also demonstrated a considerable between-assay divergence in traceability of calibration and accuracy. The evidence of noncommutability of the sera attributable to processing, however, indicates that the interpretation should be treated with caution.Conclusions: Frozen sera can be used for documenting/ validating traceability of total thyroid measurements. The way in which the sera are processed may jeopardize commutability, however, and therefore requires indepth investigation. (c) 2005 American. Association for Clinical Chemistry.