Relationship between biological variation and delta check rules performance

Objectives: The performance of delta check rules has been considered to be dependent on the biological variation characteristics of the analyte of interest. The assumed relationships have not been formally studied. The mathematical relationship between biological variation and delta check rules is explored in this study. Design and methods: From the mathematical model for absolute difference delta check, the threshold for specificity and sensitivity are observed to be normalized differently. For specificity, the threshold is normalized by the within-subject biological variation (expressed as a coefficient of variation, CV_i), whereas for sensitivity the threshold is normalized by the between-subject biological variation (expressed as a coefficient of variation, CV_g). This highlights the different roles the two biological variations play in affecting the absolute difference distribution for correct and switched patient samples. Analogous to absolute difference delta checks, for relative difference delta checks, the expressions for specificity and sensitivity are scaled by CV_i and CV_g, respectively. However, the expressions are independent of μ_g(the average of the population). Results: A comparison between the mathematical model and empirical/ historical laboratory data obtained from patients was conducted for both absolute and relative difference delta checks. In general it was found that the specificity obtained from the historical laboratory data was less than the model predicted values, while on the other hand, good correspondence was obtained between the experimental sensitivity and predicted sensitivity. Conclusions: The difference in within-subject biological variation in different patients may contribute to the observed discrepancy in predicted and empirical delta check performance.