References
NEH
GILBERT, SENSITIVITY
Stochastic interventional vaccine efficacy (SVE) estimates against COVID-19 with hypothetical shifts in geometric mean D57 antibody marker level. SVE, with 95% confidence intervals, for D57 (Binary principal surrogate vaccine efficacy (VE) against COVID-19 by D57 antibody marker greater than vs. less than or equal to the designated cut-point (median value). The black dot in each panel corresponds to the VE estimate for the relevant D57 antibody marker subgroup (Low or High) for (Continuous principal surrogate vaccine efficacy (VE) against COVID-19 by D57 marker level, with ignorance intervals (dark blue) and 95% estimated uncertainty intervals (light blue) under the No Early Harm (NEH) assumption shown for the sensitivity parameter β assumed to fall in the range [−log(4), 0]. Results are shown for (Four statistical frameworks for assessing an immune marker measured at a post-vaccination time point as an immune correlate of protection (CoP) against a clinical outcome from a vaccine efficacy trial, all of which were applied to the COVE trial.* This objective/definition attains in studies where all placebo recipients have the same value of the immune marker. This occurs in COVE, as baseline negative placebo recipients all have antibody levels to SARS-CoV-2 antigens that are below the assay detection limit. For VE trials where placebo recipients have variability in the immune marker (i.e., studies that enroll individuals previously infected with the pathogen), the objective/definition must be updated: to assess the VE that would be observed under a hypothetical intervention that assigns all participants to the vaccine arm and to a specific value of the marker, as opposed to assigning all participants to placebo and to a specific value of the marker.Principal surrogate correlates of vaccine efficacy (VE) results by Gilbert et al. method [* Sensitivity parameter settings were: None, β sensitivity parameters βPrincipal surrogate correlates of vaccine efficacy results by the Huang, Zhuang, and Gilbert method [CI, 95% confidence interval; EUI, 95% estimated uncertainty interval; IGI, ignorance interval. alpha = percentile of marker in vaccine recipients.