Methodical Considerations

This chapter considers the statistical evaluation of vaccine efficacy based on randomized, controlled, preventive vaccine efficacy trials. After defining concepts and target parameters for measuring vaccine efficacy, the remainder of the chapter focuses on studying unconditional vaccine efficacy to reduce susceptibility to pathogen infection or disease, measured cumulatively over time. A unified approach to studying how this type of vaccine efficacy depends on the following four factors is presented: baseline participant characteristics, biomarkers measuring immune responses to vaccination, genotypic and phenotypic characteristics of exposing pathogens, and time since vaccination. Statistical issues and design and analysis techniques for learning about such correlates of vaccine efficacy are discussed, including on the use of high-dimensional assays such as whole genome transcriptomic and mass cytometry assays.