In the UK, Clinical laboratories are accredited by the UK Accreditation Service, conforming to Clinical Pathology Accreditation standards – incorporating the guidelines of ISO15189:2012. These guidelines are the third version of the ISO standard set up by Technical committee ISO/TC 212 and are responsible for the competence and mechanisms of quality management related specifically to medical laboratories.
As approximately 7.3% of laboratory errors are attributable to the analytic process, CPA (2009) standard F3.3 states, “The laboratory shall determine the uncertainty of results, where relevant and possible”. In addition, ISO15189:2012 section 18.104.22.168. requires the analysis of “Measurement uncertainty of measured quantity values”.
Analytical uncertainty and variation in reported results may arise from:
(a) Analytical bias
(b) Biological variation
(c) Measurement Uncertainty (MU)
A full and comprehensive assessment of the assay performance is required in order to inform requesting clinicians of the clinical utility and quality of the results.
Routinely, Internal QC (IQC) is used to assess, and detect at an early stage, analytical error propagated through patient results and suggest early intervention to suitable well-trained laboratory personnel. Analytical bias is routinely monitored as an on-going process by internal and external quality control and assurance schemes. Corrective actions are unable to remove MU. It is present in all reported results and cannot be corrected for. As such, the quantification of uncertainty gives the requesting clinician a range around the defined result within which the result is expected to fall with a specified level of confidence (customarily reported as a 95% confidence interval).
As such, a means by which the “confidence” of the accuracy of the result is required to inform users of the quality of the result being produced in the laboratory; and how that result can be related to published reference intervals and clinically significant changes in results. Two parameters are needed in order to quantify MU;
- The interval
- The confidence level.
The uncertainty estimate therefore describes the range around a reported result within which the true value can be expected to lie within a defined level of probability. This is termed the Measurement Uncertainty (MU).