The Dutch colon cancer screening programme as an example of adopting indirect-outcome-based analytical performance specifications using a virtual analyser concept

Abstract To ensure reported laboratory results are of adequate quality, it is paramount that the set analytical performance specifications (APS) are tailored to the intended uses of the measurand. For measurands with a pivotal position in the clinical pathway, APS should be set based on clinical outcome. This paper, written as a result of an outcome-based-APS-summit in Prague, gives practical guidance on how to set outcome-based APS. Two approaches are mentioned with distinct starting points of the required performance (how much clinical misclassification do we allow, and which APS fulfils that premise) or the current performance (what is the effect of the current analytical performance characteristics (APC) on how much misclassification occurs). Importantly, APS should not just be set, but also requires monitoring, which method depends on the utilization of the test in clinical practice. The laboratory can monitor APS for so-called mother-daughter systems, individual analysers or a virtual-analyser system. This paper discusses the pros and cons of these approaches. To highlight the scope of clinically consequential outcomes for which APS can be set and monitored, the Faecal Immunochemical Testing for human haemoglobin (FIT), used for the Dutch Colorectal Cancer Screening programme (CRC-Screening), is used as an example. Here, APS were based on a clinically consequential intermediate outcome, i.e. analytically induced variability in colonoscopy referral rate (±0.5 %), and implemented as a virtual analyser system, dividing the APS budget of 10 % equally across four sources of FIT variation: reagent/calibrator lot variation, sampling buffer lot variation, within-analyser variation, and between-analyser variation.