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.