Between group comparison of AUC in clinical trials with censored follow-up: Application to HIV therapeutic vaccines

Marie Alexandre (1, 2, 3) , Mélanie Prague (1, 2, 3) , Rodolphe Thiébaut (1, 2, 3)

1 BPH - Bordeaux population health
2 SISTM - Statistics In System biology and Translational Medicine
3 VRI - Vaccine Research Institute [Créteil, France]

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 adhoc approaches and to a nonparametric method through a simulation study based on two-armed trial where trajectories and the proportion of missing data were varied. Simulation results highlights 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.

Mots clés: area under the curve; longitudinal data; statistical test; mixed-effects model; study drop out; left-censoring

Domaines: Statistiques [stat]; Méthodologie [stat.ME]

Marie Alexandre, Mélanie Prague, Rodolphe Thiébaut. Between group comparison of AUC in clinical trials with censored follow-up: Application to HIV therapeutic vaccines. Statistical Methods in Medical Research, 2021, ⟨10.1177/09622802211023963⟩. ⟨hal-03241637v2⟩