Limitations to the development of Milan model 1b analytical performance specifications

A widely accepted approach to setting Analytical Performance Specifications (APS) in laboratory medicine is the Milan models. Milan model 1b is an approach where APS are developed based on patient classification, or clinical decision-making, noting that these factors link to the probability of patient outcomes. This paper describes limitations that should be considered for any APS derived using model 1b, based on any available information from model 2 (biological variation), and model 3 (state of the art). It is also proposed that "state of the art", when defined as being tests which are routinely available, influences studies based on clinical surveys as this the background used by doctors to develop their clinical experience, as well as the ability for the APS to be put into routine use. Additionally, when "state of the art" is defined as the method used in an outcome study, this becomes a reference where such studies cannot support a smaller assay precision, as the assay performance is only one aspect of the variation in the links between laboratory results and clinical findings. Model 1b studies remain a key approach to assigning clinical meaning to assay performance, however outcomes of these studies need to be taken with awareness of relevant limitations.