Multicentric reference values for some quantities measured with Tina-Quant reagents systems and RD/Hitachi analysers.

Ten clinical laboratories in different regions of Spain have shared the search for reference individuals and the production of reference values for quantities concerning ferritin, transferrin, rheumatoid factors, C-reactive protein and antistreptolysin O, using Tina-Quant reagents systems and RD/Hitachi analysers. All the logistic work has been done in co-operation with the supplier of the reagents and analysers (Roche Diagnostics España, S.L., Barcelona). The reference limits produced in the virtual laboratory are derived from the blend of reference values obtained by each laboratory. The multicentric reference limits were estimated according to the recommendations of the International Federation of Clinical Chemistry. The work done is a model of co-operation between the in vitro diagnostic industry and clinical laboratories for the production of reference values.

Regional reference values for some quantities measured with the ADVIA Centaur analyser. A model of co-operation between the in vitro diagnostic industry and clinical laboratories.

This work is a model of co-operation between the in vitro diagnostic industry and clinical laboratories for the production of reference values. Thirteen clinical laboratories having an ADVIA Centaur analyser and representing the majority of the geographical regions of Spain have shared the search for reference individuals and the production of reference values for thyrotropin, free thyroxine, free triiodothyronine, cobalamine and folate concentrations in serum. All the logistic work has been done in co-operation with the Spanish supplier of the ADVIA Centaur analyser. The reference limits produced in the virtual laboratory are derived from the blend of reference values obtained by each laboratory. The multicentre reference limits were estimated according to the recommendations of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC).

Indirect reference limits estimated from patients' results by three mathematical procedures.

Presently, only a few clinical laboratories produce their own reference values, while the great majority use reference intervals reported in the literature. An alternative to this unsatisfactory situation is to estimate indirect reference limits by means of mathematical/statistical procedures from patients' results obtained routinely in the laboratory. The procedures of Bhattacharya (A simple method of resolution of a distribution into Gaussian components. Biometrics 1967;23:115-135) Martin et al. (Reference values based on populations accessible to hospitals. In: Gräsbeck R, Alström T, editors. Reference Values in Laboratory Medicine. Chischester: Wiley, 1981:233-262) and Kairisto et al. (Generation of reference values for cardiac enzymes from hospital admission laboratory data. Eur J Clin Chem Clin Biochem 1994;32:789-796) were applied to 14 biochemical quantities. In order to verify these procedures, the indirect reference limits obtained from patients' results were validated by statistical comparison with reference limits estimated from a reference sample according to recommendations of the International Federation of Clinical Chemistry (IFCC). Calculated indirect reference limits for most quantities studied were reliable, but indirect reference limits for bilirubins and potassium ion substance concentrations, alanine aminotransferase, and aspartate aminotransferase catalytic concentrations in serum were not suitable. We conclude that indirect reference limits can be obtained from patients' results by all procedures studied when skewness and kurtosis of mixed distribution are not too large, but other factors also seem to have an influence on the reliability of these procedures.

Multicentric reference values: shared reference limits.

In order to obtain shared reference limits, three laboratories in the same geographical area with a homogeneous population have developed a proposal to produce multicentric reference values. The strategy simulates a virtual laboratory, actually formed by the laboratories involved; the reference limits produced in the virtual laboratory are in fact derived from the blend of reference values obtained by each laboratory. Each laboratory has chosen its own reference sample and has measured the biochemical quantities under study. Reference individuals (n = 171) and 15 biochemical quantities among the most measured in clinical laboratories were selected. The reference values obtained in each laboratory were blended when permitted by the Harris & Boyd test (Clin Chem 1990; 36:265-70). The multicentric reference limits obtained by the virtual laboratory for each quantity were estimated according to the recommendations of the International Federation of Clinical Chemistry. For each quantity, each laboratory, with the results observed in their reference sample, estimated the diagnostic specificity, using as cut-off values the corresponding multicentric reference limits. Each observed value of diagnostic specificity was compared with the theoretical diagnostic specificity value, equal to 0.975, that should be observed when a reference limit is used as cut-off value. The multicentric reference limits obtained by the virtual laboratory are valid in all cases with the exception of the upper reference limit for the concentrations of calcium(II) and urate in serum in one of the laboratories.