Causal Identification

Several key assumptions cannot be tested when immunobridging trials lack clinical endpoints. Task I identification requires consistency, randomization, sequential ignorability, positivity, and baseline covariate overlap. The framework adds assumptions of approved-vaccine exchangeability across trial settings and no controlled direct effect between investigational and approved vaccines conditional on covariates and immune marker. No controlled direct effects is described as the most important and biologically fragile assumption. Poor overlap may require restricting the target population or extrapolating beyond observed support.