HHE Pathology 2019 | Page 11

for these differences, and these can be summarised as follows: • Companies: There are many IVD method manufacturers around the world. Their individual methods may have different specimen requirements; employ different method designs and use different signal detection systems. Variability may also be introduced by local modification to a company product • Components: Methods may use different calibrators; different enzymes and substrates; different antigens and antibodies; and a variety of other reagents • Conditions: Different methods have variability in reaction time; temperature, pH and often use different software and curve fits to derive results • Common target: Although methods will quote figures for imprecision and accuracy (trueness) these are of limited value unless they can be related to a common, international reference system. Patients are entitled to believe that all methods for the same analyte will give similar results on a single specimen. Sadly, for many analytes this is not currently the case Traceability in laboratory medicine Metrology is the science of measurement. The application of metrology provides the key to reducing measurement variability by facilitating the adoption of international reference systems to enable alignment from different methods. The increasing application of metrological traceability in laboratory medicine (TLM) to underpin those reference systems is reducing the variables that are responsible for methods giving different results. 6 TLM is an important area of laboratory science that is often poorly understood. Achieving TLM is a global multi-stakeholder, cooperative activity involving metrologists; international standards organisations; scientific and clinical experts from international professional bodies; healthcare regulators; and the IVD industry. 7 Metrological traceability is defined as the property of a measurement result, which can be related to a reference standard through a documented unbroken chain of calibrations. The principles of a reference measurement system for establishing metrological traceability are described in the relevant International Standards Organisation (ISO) document. 8 The components of a reference measurement system comprise reference materials (calibrators) and reference measurement procedures (methods), both of which exist at different hierarchical levels. The inter-relationship between the components of a reference measurement system may be described in the metrological traceability chain. 8 Figure 1 depicts this traceability chain with higher order reference materials and measurement procedures at the top and lower order towards the bottom. At the top of the chain is the definition of the measurand, the substance intended to be measured, expressed in SI units. The hierarchy of reference materials and measurement procedures is depicted by the rising metrological traceability arrow. Descent through the traceability chain is accompanied by increasing measurement uncertainty as depicted by the downward arrow. Figure 1 also depicts the contributions to TLM of the metrology institute or reference laboratory; the IVD method manufacturer; and the routine service laboratory. The relevance of TLM may be explained by FIGURE 1 The metrological traceability chain Definition of measurand: concentration in SI units Primary reference material Primary reference measurement procedure Secondary reference measurement procedure Secondary calibrator Manufacturer master calibrator Manufacturer standing measurement procedure IVD method manufacturer Product calibrator Manufacturer standing measurement procedure Patient result Routine laboratory method Adapted from EN ISO 17511 2003 8 11 HHE 2019 | hospitalhealthcare.com Routine lab Metrology institute / Reference lab Primary calibrator