Implementation of standardization in clinical practice: not always an easy task

Abstract

As soon as a new reference measurement system is adopted, clinical validation of correctly calibrated commercial methods should take place. Tracing back the calibration of routine assays to a reference system can actually modify the relation of analyte results to existing reference intervals and decision limits and this may invalidate some of the clinical decision-making criteria currently used. To maintain the accumulated clinical experience, the quantitative relationship to the previous calibration system should be established and, if necessary, the clinical decision-making criteria should be adjusted accordingly. The implementation of standardization should take place in a concerted action of laboratorians, manufacturers, external quality assessment scheme organizers and clinicians. Dedicated meetings with manufacturers should be organized to discuss the process of assay recalibration and studies should be performed to obtain convincing evidence that the standardization works, improving result comparability. Another important issue relates to the surveillance of the performance of standardized assays through the organization of appropriate analytical internal and external quality controls. Last but not least, uncertainty of measurement that fi ts for this purpose must be defi ned across the entire traceability chain, starting with the available reference materials, extending through the manufacturers and their processes for assignment of calibrator values and ultimately to the fi nal result reported to clinicians by laboratories.

Harmonization in laboratory medicine: the complete picture

“…The uncertainty of measurement must be ' defined across the entire traceability chain , starting with the provider of reference materials, extending through the diagnostic manufacturers and their processes for assignment of calibrator values, and ultimately to the final result reported to clinicians by end users (i.e., the clinical laboratories) ' [ 19 ]. This approach should be applied to every analyte measured in the clinical laboratory so as to understand whether the current status of the uncertainty budget of the measurement associated with the proposed metrological traceability chain is suitable for clinical application of the test itself [ 20 ].…”

“…Therefore, if analytical standardization is not followed by the appropriate revision of reference values and decision limits, pivotal to making the correct interpretation and clinical utilization of laboratory data, patients ' outcomes will be worsened. In a recent paper, Panteghini demonstrated this issue by describing three effective examples: serum creatinine and glomerular filtration rate equations, the prostate-specific antigen recalibration, and glycated hemoglobin [ 19 ].…”

Strategies to define performance specifications in laboratory medicine: 3 years on from the Milan Strategic Conference

“…Measurement uncertainty should in principle be within limits based on medical relevance making the results clinically acceptable and reliable for clinical decision-making and patient management [1]. If PS are not objectively defined and fulfilled, there is a risk of letting the variation in laboratory result overwhelm the clinical information supplied, even causing negative effects on patients' outcomes [2,3]. What degree of quality is needed to guarantee patient safety should therefore be precisely defined and specified for each analyte.…”

Performance criteria for combined uncertainty budget in the implementation of metrological traceability

“…Time, laboratory location and the assay system used to produce them should not influence patient results. There is now an international agreement on the fact that, to become equivalent for long-term, results must be traceable to higher order references [1]. In this regard, it is essential to build an unbroken metrological traceability chain whereby in vitro diagnostics (IVD) manufacturers can implement a reliable transfer of the measurement trueness from the highest level of the metrological hierarchy to calibrators of commercial analytical systems used in clinical laboratories and, finally, to the patient's results.…”