Comparing HIV Vaccine Immunogenicity across Trials with Different Populations and Study Designs

Abstract: Safe and effective preventive vaccines have the potential to help stem the HIV epidemic. The efficacy of such vaccines is typically measured in randomized, double-blind phase IIb/III trials and described as a reduction in newly acquired HIV infections. However, such trials are often expensive, time-consuming, and/or logistically challenging. These challenges lead to a great interest in immune responses induced by vaccination, and in identifying which immune responses predict vaccine efficacy. These responses are termed vaccine correlates of protection. Studies of vaccine-induced immunogenicity vary in size and design, ranging from small, early phase trials, to case-control studies nested in a broader late-phase randomized trial. Moreover, trials can be conducted in geographically diverse study populations across the world. Such diversity presents a challenge for objectively comparing vaccine-induced immunogenicity. To address these practical challenges, we propose a framework that is capable of identifying appropriate causal estimands and estimators, which can be used to provide standardized comparisons of vaccine-induced immunogenicity across trials. We evaluate the performance of the proposed estimands via extensive simulation studies. Our estimators are well-behaved and enjoy robustness properties. The proposed technique is applied to compare vaccine immunogenicity using data from three recent HIV vaccine trials.