HIV Working Group

Peter Gilbert, Ph.D
Professor, Vaccine and Infectious Disease/Public Health Sciences Divisions of the Fred Hutchinson Cancer Research Center, and Department of Biostatistics, University of Washington

“Assessing Immunological Biomarker Surrogate Endpoints in COVID-19 Vaccine Efficacy Trials”

ABSTRACT: An objective of phase 3 preventive COVID-19 vaccine efficacy trials is to assess post-vaccination immunological biomarkers as various types of “immune correlates of protection,” with applications including to identify predictors/signatures of COVID-19 risk, modifiers of vaccine efficacy, and mediators of vaccine efficacy, and ultimately to define surrogate endpoints that can constitute the basis for traditional or accelerated approval, as well as for making bridging predictions of vaccine efficacy to new conditions different from those in the phase 3 trial. In this talk I will summarize the current statistical analysis plan of the COVID-19 Prevention Trials Network for assessing immune correlates of protection. Issues addressed include immunological biomarker sampling design, biomarker selection and optimization, methods for combining biomarkers to develop best predictors of study outcomes, principal stratification approaches to assessing vaccine efficacy moderation, causal mediation approaches to assessing the proportion of vaccine efficacy mediated through one or more biomarkers, a causal interventional approach that assesses how much mean outcome risk would be altered by stochastically shifting the biomarker distribution upwards, and meta-analysis of a set of phase 3 trials.