Harmonization: the sample, the measurement, and the report

Abstract

Harmonization of clinical laboratory results means that results are comparable irrespective of the measurement procedure used and where or when a measurement was made. Harmonization of test results includes consideration of pre-analytical, analytical, and post-analytical aspects. Progress has been made in each of these aspects, but there is currently poor coordination of the effort among different professional organizations in different countries. Pre-analytical considerations include terminology for the order, instructions for preparation of the patient, collection of the samples, and handling and transportation of the samples to the laboratory. Key analytical considerations include calibration traceability to a reference system, commutability of reference materials used in a traceability scheme, and specificity of the measurement of the biomolecule of interest. International organizations addressing harmonization include the International Federation for Clinical Chemistry and Laboratory Medicine, the World Health Organization, and the recently formed International Consortium for Harmonization of Clinical Laboratory Results (ICHCLR). The ICHCLR will provide a prioritization process for measurands and a service to coordinate global harmonization activities to avoid duplication of effort. Post-analytical considerations include nomenclature, units, significant figures, and reference intervals or decision values for results. Harmonization in all of these areas is necessary for optimal laboratory service. This review summarizes the status of harmonization in each of these areas and describes activities underway to achieve the goal of fully harmonized clinical laboratory testing.

Keywords: Commutability; Harmonization; Standardization; Traceability.

Fig. 1

Components of a complete reference system showing traceability of results from a routine measurement procedure to higher order reference system components based on international standardization for organization (ISO) standard 17511:2003 [7]. Abbreviations: SI, international system of units; IDMS, isotope dilution mass spectrometry.

Fig. 2

Components of a reference system showing traceability of results from a routine measurement procedure that ends at a secondary reference material based on ISO Standard 17511:2003 [7].

Fig. 3

Representation of the concept of commutability of reference materials with authentic clinical samples between two measurement procedures. Panel A shows that commutable reference materials have the same relationship as clinical samples, and panel B shows that non-commutable materials have a different relationship. Used with permission from reference 24.

Fig. 4

Representation of differences in results for patient samples when measured by two different procedures that use a non-commutable reference material, such as shown in Fig. 3B, as a common calibrator.

Fig. 5

Assessment of suitability of a common reference interval for different routine measurement procedures for calcium using data from 33 reference interval subjects measured by 24 laboratories using 8 platforms (at least 3 laboratories participated per platform) and acceptance criteria from the Royal College of Pathologists of Australasia Quality Assurance Program [45]. (A) almost all results for calcium fell within the allowable limits of agreement (±0.1 mmol/L up to 2.5 mmol/L and ±4% when >2.5 mmol/L variation from the all methods mean) (B) the regression lines were all within the allowable limits of performance for the eight routine measurement procedures that were evaluated. (A) is used with permission from reference . (B) is used with permission from a study performed by the Harmonisation Group of the Australasian Association of Clinical Biochemists (www.aacb.asn.au/professionaldevelopment/harmonisation).