Standardization of CLMPs has been accomplished for several measurands for which primary (pure substance) reference materials exist and/or reference measurement procedures (RMPs) have been developed.
However, many of the current reference materials available for category 4 measurands have not been validated for commutability with clinical samples, and CLMPs with traceability to such materials have been shown to produce nonharmonized patient sample results for several measurands (9-12).
Harmonization may require modification of existing CLMPs, or development of new CLMPs to improve specificity for the molecular form(s) of greatest clinical importance.
In 1967 Radin proposed calibration traceability to reference standards to achieve harmonization among results from different CLMPs (18).
Calibration of routine CLMPs to be traceable to a commutable reference material produces harmonization of results for patient samples.
Establishing calibration traceability to noncommutable reference materials produces differences in calibration and nonharmonization among results from different CLMPs (19, 23, 24).
that good experimental design was followed, particularly in relation to the number and quality of patient samples, and the number of different CLMPs included.
An assessment of all CLMPs should be performed by using a panel of individual samples from people who are healthy, those who are diseased, and those who have related pathological conditions that may influence the measurand.
The assessment may demonstrate that attempts to produce equivalency of measurement results will not likely succeed because the measurand is biochemically heterogeneous and various CLMPs are measuring different measurands (e.
In many cases, reference materials are needed with well-characterized attributes, including molecular forms of interest either as measurands or as interfering substances, to validate suitability of CLMPs.
The Harmonization Implementation Group would develop the criteria for acceptable agreement among CLMPs, the technical plan, any needed reference materials, and implement procedures to achieve harmonization.