Abstract
Placebo-controlled randomized trials are widely regarded as the gold standard in clinical research. However, their routine application in infant vaccine studies has not been systematically re-evaluated in light of advances in immunology, trial design, and ethical frameworks. Infants lack the cognitive capacity required for classical placebo effects, and primary vaccine endpoints—such as immunogenicity, laboratory-confirmed infection, and severe disease—are inherently objective and biologically determined.
Although caregiver-mediated behavioral biases may influence certain outcomes, these effects are limited in scope and can be mitigated through alternative methodological approaches. We propose that placebo control in infant vaccine trials should not be considered a default requirement, but rather a context-dependent tool. A shift toward endpoint-driven trial design would better align methodological rigor with biological plausibility and ethical considerations.
Keywords
Infant vaccines, Placebo control, Immunobridging, Correlates of protection, Clinical trial design, Vaccine ethics