Specifications for trueness and precision of a reference measurement system for serum/plasma 25-hydroxyvitamin D analysis.

BACKGROUND: The divergence in analytical quality of serum/plasma 25-hydroxy-vitamin D analysis calls for defining specifications for a reference measurement system.
METHODS: Fundamentally, in a reference measurement system, there should be a relationship between the analytical specifications for higher- (reference) and lower-order (routine) measurements. Therefore, when setting specifications, we started with limits for routine imprecision (CV(rou)) and bias (B(rou)) using 4 models: (1) the misclassifications in diagnosis, (2) biological variation data (reference interval (RI) and monitoring), (3) expert recommendations, and (4) state-of-the-art performance. Then, we used the derived goals to tailor those for reference measurements and certified reference materials (CRMs) for calibration by setting the limits for CV(ref) at 0.5 CV(rou), B(ref) at 0.33 B(rou)(,) max. uncertainty (U(max)) at 0.33 B(ref).
RESULTS: The established specifications ranged between CV(rou)<or=22%, B(rou)<or=10%, CV(ref)<or=11%, B(ref)<or=3.3%, U(max) 1.1% (model 3) and CV(rou)<or=4%, B(rou)<or=2.6%, CV(ref)<or=2%, B(ref)<or=0.9%, U(max) 0.3% (model 2, monitoring).
CONCLUSIONS: Model 2 (monitoring) gave the most stringent goals, model 3, the most liberal ones. Accounting for state-of-the-art performance and certification capabilities, we used model 2 (RI) to recommend achievable goals: for routine testing, CV(rou)<or=10%, B(rou)<or=5%, for reference measurements, CV(ref)<or=5%, B(ref)<or=1.7%, and for CRMs, U(max) 0.6%.