Vaccine Efficacy: The Virion's Perspective

• Activity Number: 534
• Type: Invited
• Date/Time: Wednesday, August 6, 2014 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Dean Follmann*+ and Chiung-Yu Huang
• Companies: NIAID and Johns Hopkins University
• Keywords: Cox Regressiont ; Empirical Processes ; HIV ; Horvitz-Thompson Estimator ; Martingale

Abstract

Traditional vaccine clinical trials use the time to consequential human infection as the primary endpoint. A common method of analysis for such trials is to compare the times to infection between the vaccine and placebo groups using a Cox regression model. With new technology we can additionally record the precise number of virions that cause infectoin, say X, rather than just the indicator of infection, X>0. In this paper we develop a unified approach for randomized placebo controlled vaccine trials that couples the time to infection with the number of infecting or founder viruses. We assume that the time from randomization to a potentially infectious exposure follows the same proportional hazards model in both the placebo and vaccine groups. We allow unspecified distributions for X=0,1,2,... We denote the placebo and vaccine means of X by M, M D respectively. Thus 1- D is a measures the proportion reduction in the mean number of infecting virions due to vaccination. We develop different semi-parametric methods of estimating D which is based on the Xs from all potentially infectious encounters, even though potentially infectious encounters that result in no in