Analytical performance specifications for combined uncertainty budget in the implementation of metrological traceability

Abstract

Abstract In addition to the correct implementation of calibration traceability, the definition and fulfillment of maximum allowable measurement uncertainty (MAU) are essential in assuring that laboratory measurements are clinically usable. Across the entire calibration hierarchy, three major contributors to the measurement uncertainty (MU) budget are identified, starting with the higher-order reference providers, extending through the in vitro diagnostic (IVD) manufacturers and their processes for assigning calibrator values, and ending with medical laboratories generating the random variability of results reported to clinicians. To understand if it is possible to achieve MAU and, consequently, to fix the possible drawbacks, the definition of combined MU budget limits across the entire calibration hierarchy has a central role. In particular, quality specifications for MU of reference and commercial calibrator materials should be defined according to the MAU on clinical samples. All involved stakeholders (i.e., higher-order reference providers, IVD manufacturers, medical laboratories) should be prepared to improve their performance whenever the clinical application of the test is made questionable by the failure to achieve MAU.