Immunobridging Formula for Predicting Vaccine Efficacy, Accounting for Baseline Covariates, Post-Baseline Biomarker Surrogate Endpoints, and Geno/Serotypes of Circulating Pathogens

• Activity Number: 632
• Type: Topic Contributed
• Date/Time: Thursday, August 7, 2014 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Peter Gilbert*+
• Companies: Fred Hutchinson Cancer Research Center
• Keywords: Surrogate endpoint ; Vaccine efficacy trial ; Generalizability ; Principal stratification ; Competing risks failure time data

Abstract

This talk proposes a general immuno-bridging formula that incorporates four critical parameters affecting vaccine efficacy (VE) ? time-variations, the dependency of VE on characteristics of the failure event (i.e., genetic features of the pathogen establishing infection), the dependency of VE on baseline covariates such as host immune genetics, and the dependency of VE on post-baseline surrogate endpoints (i.e., immune responses measured in response to vaccination). The talk describes a major application of the immuno-bridging formula ? to predict the efficacy of a candidate vaccine/treatment in a new setting not considered in the original vaccine efficacy trial. The application is illustrated by the process of the HIV Vaccine Trials Network to build on a landmark RV144 trial result in 2009 that showed partial vaccine efficacy of a pox-protein HIV vaccine regimen, for studying a refined version of this vaccine regimen in South Africa.