Randomized clinical trials in the presence of diagnostic uncertainty: Implications for measures of efficacy and sample size

Diagnostic uncertainty, particularly prior to the receipt of test results, is common in medicine. When randomized trials are being conducted to evaluate therapies in these situations, patients must be randomized in the absence of a definitive diagnosis. This article explores some of the implications of diagnostic uncertainty for the design and analysis of randomized clinical trials, using specific therapeutic examples to illustrate the important points.