Quantifying the bias associated with use of discrepant analysis.

Discrepant analysis is a widely used technique for estimating the performance parameters of a laboratory test. In discrepant analysis, each specimen is initially tested with the candidate test and a comparison method, and when the results of the two tests disagree, a confirmatory test is used to resolve the discrepancy. Discrepant analysis usually produces biased estimates. This report quantifies this bias and shows that it is usually positive, leading to overestimation of the performance parameters of a laboratory test. The direction and magnitude of the bias are predictably influenced by the analytical sensitivity and specificity of the candidate test, comparison method, and confirmatory test. The proportion of abnormal specimens tested also affects the magnitude of the bias, particularly the estimates of analytical sensitivity and positive predictive value when this proportion is low. Alternative approaches are suggested.