Between and within calibration variation: implications for internal quality control rules

The variability between calibrations can be larger than the within calibration variation for some measurement procedures, that is a large CV_between:CV_within ratio. In this study, we examined the false rejection rate and probability of bias detection of quality control (QC) rules at varying calibration CV_between:CV_within ratios. Historical QC data for six representative routine clinical chemistry serum measurement procedures (calcium, creatinine, aspartate aminotransferase, thyrotrophin, prostate specific antigen and gentamicin) were extracted to derive the CV_between:CV_within ratios using analysis of variance. Additionally, the false rejection rate and probability of bias detection of three 'Westgard' QC rules (2:2S, 4:1S, 10X) at varying CV_between:CV_within ratios (0.1-10), magnitudes of bias, and QC events per calibration (5-80) were examined through simulation modelling. The CV_between:CV_within ratios for the six routine measurement procedures ranged from 1.1 to 34.5. With ratios >3, false rejection rates were generally above 10%. Similarly for QC rules involving a greater number of consecutive results, false rejection rates increased with increasing ratios, while all rules achieved maximum bias detection. Laboratories should avoid the 2:2S, 4:1S and 10X QC rules when calibration CV_between:CV_within ratios are elevated, particularly for those measurement procedures with a higher number of QC events per calibration.