Effect of investigator bias on the significance level of the Wilcoxon rank-sum test

Abstract

When using subjective ordered categorical variables to measure the efficacy of an active treatment versus placebo in a double-blind clinical trial setting, bias may be introduced into the response variables when investigators become partially or totally unblinded to treatment assignment due to characteristic side effects. The investigators may alter the classification of a patient's response to treatment based on perceived treatment assignment. The introduction of bias leads to a considerable increase in the actual significance level of the Wilcoxon rank-sum test.