Setting analytical performance specification by simulation (Milan model 1b)

There is presently no consensus on the acceptable reclassification rate (or other clinical performance criterion), which challenges the development of model 1b analytical performance specifications (APS). Here, simulations were performed on the NHANES IV data to obtain bias APS by constraining the clinical performance criterion as an increase in reclassification rate of 1.9 % (indirect outcomes, model 1b) and flagging rate of 1.9 % (biological variation, model 2). The bias APS by model 1b were asymmetrical at upper and lower reference limits and may be lower than model 2. This may be due to the use of actual laboratory data distribution from NHANES IV (model 1b) instead of idealized assumptions without analytical variations in model 2. Nonetheless, the APS figures obtained in this exercise were meant for illustrative purposes and may not be considered definitive APS.