Figure 1

Schematic of a vaccine trial design incorporating closeout placebo vaccination. The four horizontal lines represent four subjects (two each assigned to placebo and active vaccine at time T=0). Subjects have biomarker S _obs measured at time τ, identifying S₀ and S₁ for placebo and vaccine recipients, respectively; the counterfactual biomarker values (S₁ and S₀ respectively) remain unidentified, as indicated by ‘?’. Subjects with the solid diamond represent those infected during the trial (yielding Y₀=1 and Y₁=1). Subjects assigned to placebo and uninfected during the trial (i.e., those with Y₀=0) are eligible for closeout vaccination at the end of the study at time T=t. Post-closeout vaccination biomarker measurements S _closeout are obtained on these subjects at time T=t+τ. The dashed curved arrow represents the “time constancy” assumption that allows S _closeout to be used to identify S₁, by definition the counterfactual measurement that would have been obtained at T=τ under assignment to the active vaccine. For ease of readability, this figure does not represent subjects who were infected prior to τ (i.e., those with A^τ=0) and who would have Y=1 and S undefined.