Missing Data Methods in Hiv Clinical Trials: Regulatory Guidance and Alternative Approaches *

Abstract

Efficacy in HTV clinical trials is measured by changes in HIV RNA levels over time as well as the proportion of subjects with HIV RNA levels below an assay's threshold of reliable quantification at a single time point. Missing data arise naturally due to missed visits and premature discontinuations of treatment. The available data are then analyzed using repeated measures models and univariate comparisons of proportions, assuming missing data occur at random or considering missing values as treatment failures (worst case scenario). These and other methods recently proposed by regulatory authorities are presented along with alternative approaches. Advantages and disadvantages of each method are discussed. Data from a recent comparison of ‘standard-of-care’ triple combination regimens are used for illustration.