Roadmap for Harmonization of Clinical Laboratory Measurement Procedures

Abstract

Results between different clinical laboratory measurement procedures (CLMP) should be equivalent, within clinically meaningful limits, to enable optimal use of clinical guidelines for disease diagnosis and patient management. When laboratory test results are neither standardized nor harmonized, a different numeric result may be obtained for the same clinical sample. Unfortunately, some guidelines are based on test results from a specific laboratory measurement procedure without consideration of the possibility or likelihood of differences between various procedures. When this happens, aggregation of data from different clinical research investigations and development of appropriate clinical practice guidelines will be flawed. A lack of recognition that results are neither standardized nor harmonized may lead to erroneous clinical, financial, regulatory, or technical decisions. 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, the harmonization of clinical laboratory procedures for measurands that do not have RMPs has been problematic owing to inadequate definition of the measurand, inadequate analytical specificity for the measurand, inadequate attention to the commutability of reference materials, and lack of a systematic approach for harmonization. To address these problems, an infrastructure must be developed to enable a systematic approach for identification and prioritization of measurands to be harmonized on the basis of clinical importance and technical feasibility, and for management of the technical implementation of a harmonization process for a specific measurand.

Impact of the Choice of IGF-I Assay and Normative Dataset on the Diagnosis and Treatment of Growth Hormone Deficiency in Children

“…Harmonization can be a tool to reduce differences in test results for laboratory measurements that lack a reference measurement procedure [26, 27]. For example, harmonization of GH measurements has proven to reduce between-laboratory variation and to improve comparability in the confirmation of GHD by provocative GH testing [23, 28].…”

“…Harmonization of IGF-I results is much more complicated as clinical decision points vary significantly for age and sex and are present at both –2 SD and +2 SD. Considering the challenges that accompany the harmonization procedure of laboratory measurements, including analytical specificity for the analyte and commutability of reference material [26], it is doubtful whether harmonization of IGF-I results based on a single multiplication factor is appropriate for the diagnosis and treatment of GHD in children. To the best of our knowledge, there is no study that has demonstrated the applicability of harmonized IGF-I results in clinical practice.…”

Full method validation in clinical chemistry

“…Harmonisation is then the second best and in fact the only option. It aims at achieving equivalent results amongst different measurement procedures commonly using fresh patient samples [27][28][29][30][31]. Unfortunately, less than 10 % of measurands (60 of more than 600) in a typical university hospital laboratory of clinical chemistry and laboratory medicine are as yet traceable to SI.…”

Standardization in laboratory medicine: Adoption of common reference intervals to the Croatian population

“…Such reference intervals could be applied globally in all laboratories using methods traceable to the same reference measuring system and analysing the biological samples from populations with similar socio-demographic and ethnic characteristics [23,25] . For the complex analytes for which the laboratory test results often are not expressed in SI-, but in arbitrary units the concept of harmonization has been proposed based on the "Step-Up" design [26,27] . This essentially comprises a sequence of method comparisons with selected sets of commutable samples.…”

“…The outcome of each phase informs the decision as to whether the stepup to the next phase should be undertaken. The biggest disadvantage of this process is the limited amount of commutabile clinical samples required to maintain the process of harmonization [26,27] . In 2010, in order to launch international initiatives for the harmonization process in the laboratory medicine the International Consortium for Harmonization of Clinical Laboratory Results, (www.…”