MEASUREMENT UNCERTAINTY
time to calculate the assay CV and assign that as the MU. Here we have highlighted the complexity of the data below the imprecision method used, and some of the assumptions that drive that guidance. It is clear that work needs to continue in this field to advance our understanding in QC design so that practices align with the intended use of our QC data. That use for many years has been focused on batch acceptance, checking system alignment and very much focused on local performance. In the traceability era, that appears to be changing. As such we need to consider the information that our QC gives us and how that is applied clinically to patient results and also to quality management on a scale we have not previously had to consider.
References 1 Qin Y, Zhou R, Wang W et al. Uncertainty
Should you report uncertainties as standard deviations or as a coefficient of variation? The answer depends on the use of the result and the understanding of the behaviour of the assay under investigation.
the assay under investigation. A relative uncertainty such as the urel
(relative
standard uncertainty) from the standard deviation or the %CV (also termed the %CVrel
) are limited to being used in two conditions. In the absence of these conditions being met the absolute uncertainty is recommended. Situation 1 is when the %CV is constant
across the measurement range. The assumption that imprecision across the entire range is constant cannot be made in the absence of evidence to confirm that. It may be necessary to perform a precision profile of your test to check to see whether variation is constant across the measurement range. This may involve supplementing additional QC material at levels not challenged by the QC in use, of course ensuring maintenance of commutability when doing so. ISO/TS 20914:2019 (section 5.5) does refer to “approximately constant” and suggests two methods that can be used to assure this.
Firstly, through a comparison study and analysis using a difference plot (previous series have discussed the used of the Bland-Altman difference analysis),
or using the precision profiling method outlined in CLSI EP05-A3. If the precision is constant across the range, the %CV as a measure of the relative uncertainty can be extrapolated to any measurement on the measurement range, but again, caution is advised here. Secondly, if the result is a calculated
result the %CV is used provided that calculation is a multiplication or division. The conclusion from this is that, if the QC is based close to (within predefined regions) or ideally at a clinical decision point, a single MU value based on data at that point can be used. However, we know this is often not the case. When this isn’t possible multiple MU results should be reported, at each of the levels interrogated by the IQC.6
The same
approach is taken if the MU is sufficiently different to only apply to the area controlled.
Conclusions This article considered some of the lesser discussed points we need to think about when we calculate imprecision as a measure of uRW
towards our combined uncertainty. Practice has been for a long
We have highlighted the complexity of the data below the imprecision method used, and some of the assumptions that drive that guidance. It is clear that work needs to continue in this field to advance our understanding in QC design so that practices align with the intended use of our QC data
22
evaluation in clinical chemistry, immunoassay, hematology and coagulation analytes using only external quality assessment data. Clin Chem Lab Med. 2018 Aug 28; 56 (9): 1447–57. doi: 10.1515/cclm-2017-1199.
2 Panteghini M. The simple reproducibility of a measurement result does not equal its overall measurement uncertainty. Clin Chem Lab Med. 2022 Jul 11;60 (10): e221-e222. doi: 10.1515/cclm-2022-0618. PMID: 35802464.
3 Panteghini M. Redesigning the surveillance of in vitro diagnostic medical devices and of medical laboratory performance by quality control in the traceability era. Clin Chem Lab Med. 2022 Dec 22; 61 (5): 759–68. doi: 10.1515/cclm-2022-1257.
4 Martinello F, Snoj N, Skitek M, Jerin A. The top-down approach to measurement uncertainty: which formula should we use in laboratory medicine? Biochem Med (Zagreb). 2020 Jun 15; 30 (2): 020101. doi: 10.11613/BM.2020.020101. Epub 2020 Apr 15. PMID: 32292278; PMCID: PMC7138004.
5 Panteghini M. Analytical performance specifications for combined uncertainty budget in the implementation of metrological traceability. Clin Chem Lab Med. 2024 Feb 5. doi: 10.1515/cclm-2023- 1325. Epub ahead of print.
6 Ceriotti F. Deriving proper measurement uncertainty from Internal Quality Control data: An impossible mission? Clin Biochem. 2018 Jul; 57: 37–40. doi: 10.1016/
j.clinbiochem.2018.03.019.
Dr Stephen MacDonald is Principal Clinical Scientist, The Specialist Haemostasis Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0QQ. +44 (0)1223 216746.
MAY 2024
WWW.PATHOLOGYINPRACTICE.COM
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