Evaluation of Treatment Effect Modification by Post-randomization Biomarker-defined Principal Strata with Application to Vaccine Efficacy Trials

Abstract

In vaccine studies, investigators are often interested in studying effect modifiers of clinical treatment efficacy by biomarker-based principal strata, which is useful for selecting biomarker study endpoints for evaluating treatments in new trials, exploring biological mechanisms of clinical treatment efficacy, and studying mediators of treatment efficacy. Such post-randomization effect modification research has been referred to as principal surrogate evaluation. Towards this goal, many methods have been developed for a two-phase sampling design, motivated by trials in HIV vaccine research. However, new challenges have arisen in Dengue vaccine efficacy trials, including pre-trial disease exposure and long time span between baseline and when post vaccination antibody neutralization titers are measured. Motivated by these challenges, my dissertation research aims at addressing some limitations of existing literature and developing new methods for principal stratification effect modification analysis to accommodate broader vaccine efficacy trial designs.