MEASUREMENT UNCERTAINTY
SI unit symbol
S M
kg A K
mol Cd
Name of SI unit
second metre
kilogram Ampere Kelvin mole
candela Quantity time
length mass
electrical current temperature
amount of substance luminous intensity
Table 3. The seven base international system of units. From these, derived units can be determined
and are used for calibration. They are not often directly used by end users as the availability and cost of CRMs are often prohibitive; they are produced in national measurement institutes. The CRM is often a pure substance (such as creatinine). This substance is then needed in a form to provide commutability to patient samples so may be supplemented into a body fluid we routinely measure (eg plasma, serum). This is a matrix matched calibrator (Fig 1). The matrix is everything that is within the sample that is not the measurand of interest.
Commutability of reference materials Processing may be required to maintain stability of measurands for transport over long distances or for prolonged periods of time in reference materials. Again, commutability to patient samples must be shown when pre-processing of the calibration material (eg lyophilisation) differs from sample processing. The additional preparation steps required, such as reconstitution, mean that very stringent requirements are needed to be met in order for these pre-processing steps to be shown not to impact on the traceability chain and therefore final patient results.
Absence of reference materials – International standards and harmonisation An alternative to RMs are international standards provided by the World Health Organization, National Metrology Institutes or discipline-specific international societies. Often such material is assigned values by consensus in field studies of well-established laboratories, reference measurement laboratories or diagnostic laboratories. The consensus value is determined across a range of measurement methods, representing those that are, at the time, expected to use the material in routine clinical practice. However, often the assigned value does not have an uncertainty associated with it
in the same way an RM would. Sometimes uncertainties are provided for stability, homogeneity and vial content (these samples are often provided in lyophilised or frozen vials), but not for the assigned value.
Finally, MT can be demonstrated
according to ISO 17511:2020 when the traceability chain ends with the manufacturer calibrator, where no higher order system is available. Of course, the consequence of this is that different methods will be calibrated against different standards and different results will invariably be expected. A harmonisation approach would alleviate the risk of methods showing a lack of comparability caused by manufacturer- specific calibration being the highest level of calibration. One interesting aspect of this approach is that, according to ISO 21151, requirements for a harmonisation protocol, manufacturers may apply a correction factor through their local calibration to support harmonisation. However, this comes at a cost, as this is a bias correction and therefore source of ubias
in combined uncertainty, provided it is, as expected, included in the ucal provided with the method.
value
Locally verifying metrological traceability prospectively There is clearly a need for an ongoing verification of maintenance of the calibration hierarchy at the local laboratory level. Traceability relies on the propagation of uncertainty vertically through the calibration hierarchy. Performance in proficiency testing (PT), such as External Quality Assessment (EQA), when derived from a consensus value compares horizontally across measuring systems. Any bias recognised during PT activities is local bias, compared to the peer group rather than systematic bias of the method to the calibration hierarchy. Of course, PT remains an essential assessment of laboratory performance. The only way to ensure MT through PT is to compare to an assigned value determined using a reference method, with a complete traceability chain. In doing so we would have a certified value that could be used to compare each method, provided such a method was on the same calibration hierarchy. That means to say that the assigned value of the material is passed through the hierarchy to the final EQA result – as we would desire for a patient result.
Metrological traceability and accreditation We cannot discuss MT without referencing accreditation requirements.
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