Reference measurement systems in clinical chemistry.

BACKGROUND: In clinical chemistry, traceability of measurements is of high priority.
METHODS: In this literature review, current recommendations on the process of establishing traceability (or standardization) are critically discussed.
RESULTS: Traceability is to be established to the highest international standards by a comprehensive reference measurement system. Elementary to this system are a metrological basis, a measurement unit system, i.e., the Système International d'Unités (SI), its embodiment by a material standard and a calibration hierarchy for transfer of accuracy/trueness to the manufacturer's product calibrators and routine methods. However, for analytes lacking an unequivocally recognized entity, the International Unit (IU) and International Standard (IS) concept have been developed. On this basis, the review distinguishes between traceability of SI- and IU-analytes.
CONCLUSIONS: SI-traceability, exemplified by cortisol, is straightforward. However, special attention is needed for "free analytes" and "analyte families". For traceability of IU-analytes, exemplified by hCG, the standardization process passes different phases in function of the history of the analyte (discovery, ISs, measurement by bioassays/immunoassays, complete structure elucidation). However, perspectives to the development of an SI-based reference measurement system are realistic. Last but not least, for successful global implementation of the standardization process, consensus of all major players in the field will be required.