MEASUREMENT UNCERTAINTY
In ISO 15189:2022, MT is central to many aspects. Other accreditation documents are used worldwide, and the MT requirement will vary accordingly. We must specify calibration and traceability requirements for our methods, based on the importance of being able to maintain “consistent reporting of results”. Some named methods cannot demonstrate traceability so it is worth reviewing the document. Where calibrations are performed, recording the results, dates and times of the actions is essential to demonstrate the schedule being followed, and of course the actions taken following calibrations – including the use of correction factors if required. Compliance may be challenging in the absence of higher-order references or even international standards. A useful approach is to consider the individual measurement steps and demonstrate traceability of those steps, particularly those that contribute significantly to final measurement uncertainty. Things to consider are temperature, pipetting volume or other environmental or experimental variables that will significantly affect results. These are themselves often calibrated to a higher-order reference and therefore demonstrate traceability. The approach for qualitative assays should include ensuring identification is consistent with previous results if changes occur, and may even include the strength of reactions if that is derived from the method.
Where do we find the information to support traceability claims? In order for us to demonstrate traceability of our results we can first consult our manufacturer instructions for use (IFU). Depending on the material provided, an extensive certificate of analysis may also be provided. These documents accompany reagents and explain how methods were validated and to what extent those results are traceable. This will show whether the calibration hierarchy has been followed. If we are in the fortunate situation where a full calibration hierarchy is available, traceability can be assured. If not, partial hierarchies may be available, with the expected impact on
Document
ISO 17511:2020 ISO 15193:2009 ISO 15194:2009 ISO 15195:2018 ISO 21151:2020
Subject Metrological Traceability
Reference Measurement Procedures Certified Reference Materials
Reference Measurement Laboratories Harmonisation Protocols
Table 4. Documents that reference methods, materials and service must conform to in order to be accepted to the JCTLM database.
uncertainty propagation. For clinical validation of the method
a reference method is usually quoted. Calibration material will also contain information about what the manufacturer calibrator was calibrated against, and now we expect that an assigned value and associated uncertainty is provided. To verify the claims of traceability in such documentation we can consult the repository on higher-order reference materials, methods and measurement services available online (
jctlmdb.org). This website is the site of the Joint Committee for Traceability in Laboratory Medicine (JCTLM) and contains all registered reference materials and methods as well as reference laboratories that achieve standards to be required for registration (Table 4). Traceability should be checked regularly, and verified that changes in the assay, its components, including reagents and calibrations do not compromise what we may have previously verified as traceability.
Conclusions Metrological traceability is a tool to support method selection and improvement of methods if we find that we are not achieving the quality of results we require. Pasqualetti et al.1
discussed
the challenges of achieving analytical performance specifications (APS) for blood electrolytes (sodium, chloride, potassium) using biological variation targets. In this letter, the importance of the manufacturer choosing an appropriate traceability chain, and for the end- user laboratory to review that chain, is highlighted by some of the parameters listed not achieving APS using one established traceability hierarchy. This
With increased awareness of MT, both from an IVD manufacturer and end-user perspective, improvements in analytical methods are possible, even when achieving desired specifications may at first glance seem prohibitively difficult
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presents a problem as the laboratory cannot achieve expected specifications, irrespective of how good its local performance is. By switching to a different calibration hierarchy, a reduced ucal results of a lower uref
, as a , allows the laboratory
to achieve the required standard. This highlights another common pitfall with assumptions of traceability when different methods, even those provided by the same manufacturer, may not be equivalent. This can even occur when both methods are traceable to the same international standard. This is a particular challenge in some immunoassays where the same international standard may be used, but the epitopes where the antibodies bind may differ. With increased awareness of MT, both
from an IVD manufacturer and end-user perspective, improvements in analytical methods are possible, even when achieving desired specifications may at first glance seem prohibitively difficult.
Reference 1 Pasqualetti S, Chibireva M, Borrillo F,
Braga F, Panteghini M. Improving measurement uncertainty of plasma electrolytes: a complex but not impossible task. Clin Chem Lab Med. 2020 Oct 13; 59 (4): e129–e132. doi: 10.1515/cclm-2020- 1399.
Further reading n ISO 15193 – In vitro diagnostic medical
devices – Measurement of quantities in samples of biological origin – Requirements for content and presentation of reference measurement procedures.
n ISO 17511:2020 – In vitro diagnostic medical devices – Requirements for establishing metrological traceability of values assigned to calibrators, trueness control materials and human samples.
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.
01223 216746 FEBRUARY 2024
WWW.PATHOLOGYINPRACTICE.COM
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