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 (CVrou) 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 CVref at 0.5 CVrou, B-ref at 0.33 B-rou, max. uncertainty (U-max) at 0.33 B-ref. Results: The established specifications ranged between CVrou <= 22%, B-rou <= 10%, CVref <= 11%, B-ref <= 3.3%, U-max 1.1% (model 3) and CVrou <= 4%, B-rou <= 2.6%, CVref <= 2%, B-ref <= 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, CVrou <= 10%, B-rou <= 5%, for reference measurements. CVref <= 5%, B-ref <= 1.7%, and for CRMs, U-max 0.6%. (C) 2009 Elsevier B.V. All rights reserved.