MEASUREMENT UNCERTAINTY


Uncertainty of reference measurement procedures or reference materials (uref


)


measurement system, uncertainty of the assigned value (ucal


Calibration uncertainty of the )


Measuring system imprecision (Performance Characteristics)


Local laboratory performance (random variability in the laboratory)


u = RW


Fig 4. Division of the MU budget according to the traceability chain of the measurand. Defined limits are applied for each of uref


, ucal and uRW . In doing so areas for improvement can be identified.


total must not exceed 50% of the total MAU. This permits the remaining 50% to be free for the laboratory. However, it is acknowledged that these limits can be flexible, and as long as the IVD manufacturer uses up an appropriate amount of the budget to allow the local end user to remain within the total budget how it is partitioned with uref ucal can be flexible.5 – as uRW


In production, conformance to target MU is managed by minimising long term imprecision, and is therefore managed by IQC performance. uref


and ucal are not and Laboratory variation


captures hopefully, all sources of variation. Only some of these are under the control of us in the labratory. The measurement system will have a baseline performance, provided by the manufacturer. We verify our performance against this when we implement the assay. Longer term performance may of course vary with respect to these performance characteristics so actually uRW


is a measure of the manufacturer


system imprecision combined with local laboratory variation. Better understanding


of the underlying contributors to the uRW is a subject of further research. New data were presented at the CELME meeting about how to incorporate lot to lot variation, and specifications for it, in the uRW


considered to vary over time, but can be improved with method development or the implementation of an improved traceability hierarchy. ucal across calibration lots, uref


will change only when


new international standards become available. In any event, the limits set must be agreed as analytically achievable and clinically appropriate.


Conclusions


In the absence of internationally accepted limits of acceptable MU, these must be determined locally and agreed as appropriate by both the laboratory scientific leads and clinical leads. Review of MU limits and ensuring MU targets are not exceeded is at a minimum to be undertaken annually. Identification of an increase in MU over time should be thoroughly audited with root causes identified and corrected.


component. That is, however, a larger discussion we will save for another article.


The meeting in Prague was clear at the outset that APS models were not going to be changed in the meeting. The intended outcome was to discuss the


=


direction of travel for the future. A running theme throughout the two days was the need for more engagement from IVD manufacturers to provide the end user (us in the lab) with the information we need to be able to implement metrological traceability and measurement uncertainty fully. From those attending, IVD manufacturers are becoming more aware and are engaging with our requirements. I know that any I speak to are certainly aware of what I need (or some might say want!). It’s important to emphasise at this point that applying metrological traceability and MU permits a joint effort between manufacturers and end users to optimise analytical performance to reduce risk of harm to the patient, based on the clinical utility of the assay. In doing so we can improve the performance in collaboration, rather than being forced to remove assays that do not achieve specifications, occasionally because the APS are too demanding. Serum sodium is an example where improvements towards very stringent specifications have been successfully employed,5,12


alternative approaches have also been suggested to monitor performance.13


and It


is well accepted that sodium is a clinically useful measurand that has driven clinical decisions for many, many years. We also know analytical methods available support that clinical decision making. The question of clinical outcome models was also a significant point of discussion. We recognise that patient outcomes can be represented by clinical, operational and economic outcomes all of which are relevant in the health care setting.14


Whether or not outcomes can


In the absence of internationally accepted limits of acceptable MU, these must be determined locally and agreed as appropriate by both the laboratory scientific leads and clinical leads. Review of MU limits and ensuring MU targets are not exceeded is at a minimum to be undertaken annually. Identification of an increase in MU over time should be thoroughly audited with root causes identified and corrected


32


be directly attributed to analytical quality is still not completely answered. One enlightening aspect of the meeting in Prague was to emphasise the link between clinical utility of the test and the setting of APS. In particular, different clinical utilities may exist for the same measurand and therefore a one size fits all approach isn’t practical. Of course, it is also not very scientific not to consider all the applications of our tests. This aligns perfectly with ISO15189:2022 requirements, linking decisions we make in our quality processes to the clinical utility of our methods, and ultimately to mitigation of risk of harm to the patient. There is also clear disparity in the development of different disciplines in medical laboratories as to how advanced they are with applying these concepts. Certainly, the clinical biochemists have been the forerunners here, and for that the other disciplines are very grateful. However, as has always been the case other disciplines may not have the required data readily available.


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