To Harmonize and Standardize: Making Measurement Results Comparable

Clinical chemistry is a field in which the reliability of measurement results has a major impact on decisions that directly affect human beings. The conditions under which the measurements are performed and the way their results are applied bring about very stringent requirements in regard to the methods used. Measurements are expected to give reliable results after a single determination performed directly on complex matrices like serum or urine, and data should preferably be available within minutes to a few hours. The results need to be reliable (i.e., accurate) enough to enable comparisons with reference intervals and cutpoint values, and the measurement target should be a clinically significant parameter. These requirements can currently be met for hundreds of analytes. The next level of requirement is that measurement results be comparable between laboratories and methods, over time, with common reference ranges for different methods. This has been achieved only for a much smaller number of analytes. For a number of clinically relevant analytes, comparability is achieved by establishing metrological traceability to a stable reference [ Systeme International d'Unites (SI)2 or quantity values embedded in a material standard] for well-defined molecules. For the majority of clinical measurands, however, it is difficult and clinically not meaningful to describe the properties of the analyte of interest as a single chemical entity. In fact, one would need a “fuzzy” definition describing an ensemble of molecules, e.g., “The ensemble of molecular entities with sequence X, possessing on position 42 a Q instead of an E in 14% of the molecules, with an oxidized cysteine in position 98 in about 65% of the molecules, with a 3-dimensional structure such …