Analytical Performance Specifications and Their Role in Metrological Traceability for IVD Standardisation
This review examines how analytical performance specifications integrate with the ISO 17511 metrological traceability framework to ensure equivalent patient results across IVD medical devices. It demonstrates how maximum allowable uncertainty can be partitioned across calibration hierarchy steps and highlights that current internal QC practices frequently underestimate repeatability uncertainty by using insufficiently representative time intervals, potentially compromising clinical decision-making.
The original study
The role of analytical performance specifications in international guidelines and standards dealing with metrological traceability in laboratory medicine.
- Authors
- Greg Miller W
- Journal
- Clinical chemistry and laboratory medicine
- Type
- Journal Article, Review
- PMID
- 38579121
Original abstract
The goal of metrological traceability is to have equivalent results for a measurand in clinical samples (CSs) irrespective of the in-vitro diagnostic medical device (IVD-MD) used for measurements. The International Standards Organization standard 17511 defines requirements for establishing metrological traceability of values assigned to calibrators, trueness control materials and human samples used with IVD-MDs. Each step in metrological traceability has an uncertainty associated with the value assigned to a material. The uncertainty at each step adds to the uncertainty from preceding steps such that the combined uncertainty gets larger at each step. The combined uncertainty for a CS result must fulfil an analytical performance specification (APS) for the maximum allowable uncertainty (umax CS). The umax CS can be partitioned among the steps in a metrological traceability calibration hierarachy to derive the APS for maximum allowable uncertainty at each step. Similarly, the criterion for maximum acceptable noncommutability bias can be derived from the umax CS. One of the challenges in determining if umax CS is fulfilled is determining the repeatability uncertainty (u Rw) from operating an IVD-MD within a clinical laboratory. Most of the current recommendations for estimating u Rw from internal quality control data do not use a sufficiently representative time interval to capture all relevant sources of variability in measurement results. Consequently, underestimation of u Rw is common and may compromise assessment of how well current IVD-MDs and their supporting calibration hierarchies meet the needs of clinical care providers.