Nondifferential misclassification of outcome under (near-) perfect specificity: a simulation study.

Mismeasurement of a dichotomous outcome yields an unbiased risk ratio estimate when there are no false positive cases (perfect specificity) and when sensitivity is nondifferential with respect to exposure status. In studies where these conditions are expected, quantitative bias analysis may be considered unnecessary. We conducted a simulation study to explore the robustness of this special case to small departures from perfect specificity and stochastic departures from nondifferential sensitivity. We observed substantial bias of the risk ratio with specificity values as high at 99.8%. The magnitude of bias increased directly with the true underlying risk ratio and was markedly stronger at lower baseline risk. Stochastic departure from nondifferential sensitivity also resulted in substantial bias in most simulated scenarios; downward bias prevailed when sensitivity was higher among unexposed compared with exposed, and upward bias prevailed when sensitivity was higher among exposed compared with unexposed. Our results show that seemingly innocuous departures from perfect specificity (eg, 0.2%) and from nondifferential sensitivity can yield substantial bias of the risk ratio under outcome misclassification. We present a web tool permitting easy exploration of this bias mechanism under user-specifiable study scenarios.