We will evaluate existing statistical methods and develop and evaluate new statistical methods for the analysis of Phase III, HIV-vaccine efficacy trials. Primary analyses of vaccine efficacy trials will be conducted using simple statistical methods that compare attack rates in the vaccine and control groups. We will develop asymptotic distribution theory for statistical tests and estimators that will be used in primary analyses of vaccine efficacy trials under a general model for transmission of an infectious disease that will explicitly include; Dependence induced by contacts among study participants, heterogeneity in contact rates and vaccine effects, and non-random patterns of mixing among study participants. We will also develop and evaluate statistical methods for secondary analyses of HIV vaccine trials. More specifically, these methods will be for (i) the analysis of heterogeneity of vaccine effects on susceptibility to infection and for (ii) the analysis of surrogate endpoints for infectiousness and disease progression among vaccine trial participants who become infected.
