Between-group comparison of area under the curve in clinical trials with censored follow-up: Application to HIV therapeutic vaccines

Abstract

In clinical trials, longitudinal data are commonly analyzed and compared between groups using a single summary statistic such as area under the outcome versus time curve (AUC). However, incomplete data, arising from censoring due to a limit of detection or missing data, can bias these analyses. In this article, we present a statistical test based on splines-based mixed-model accounting for both the censoring and missingness mechanisms in the AUC estimation. Inferential properties of the proposed method were evaluated and compared to ad hoc approaches and to a non-parametric method through a simulation study based on two-armed trial where trajectories and the proportion of missing data were varied. Simulation results highlight that our approach has significant advantages over the other methods. A real working example from two HIV therapeutic vaccine trials is presented to illustrate the applicability of our approach.