Effect of analytical quality on establishing common reference intervals and their use

Abstract

In the Nordic Reference Interval Project (NORIP), reference intervals were established for 25 common clinical biochemical quantities. In the project, samples from more than 3000 reference individuals collected in the 102 participating laboratories from all five Nordic countries were analysed locally. In order to maintain a high level of analytical quality and to document this quality, a common calibrator/reference preparation (CAL) and a number of control samples were analysed together with the reference samples. All these materials were serum pools of unprocessed serum from many donors in order to obtain commutable materials. The CAL was used to harmonize the many different analytical procedures and calibrations by simple recalibration by the factor T/M where T is the target value based on reference methods and M is the mean of 10 replicate measurements of CAL in each laboratory. The analytical quality specifications (analytical goals) were based on specifications created directly for the purpose of sharing common reference intervals and only the bias criteria were used because bias is the dominating problem in transfer of reference intervals. These specifications were different for the evaluation of reference values to create common reference intervals and for the laboratories to use these common reference intervals (when established). An interesting outcome was that it was only for the biologically well‐regulated quantities serum‐sodium and serum‐calcium that the selection of the best laboratories gave considerably narrower reference intervals.

• Quality goal
• reference limit
• reference value