Biased efficacy estimates in phase-III dengue vaccine trials due to heterogeneous exposure and differential detectability of primary infections across trial arms

Vaccine efficacy (VE) estimates are crucial for assessing the suitability of dengue vaccine candidates for public health implementation, but efficacy trials are subject to a known bias to estimate VE toward the null if heterogeneous exposure is not accounted for in the analysis of trial data. In light of many well-characterized sources of heterogeneity in dengue virus (DENV) transmission, our goal was to estimate the potential magnitude of this bias in VE estimates for a hypothetical dengue vaccine. To ensure that we realistically modeled heterogeneous exposure, we simulated city-wide DENV transmission and vaccine trial protocols using an agent-based model calibrated with entomological and epidemiological data…

• G
  GlaxoSmithKline
• NI
  National Institutes of Health

  Awards: TR002529, UL1 TR002529, TL1 TR002531, P01AI098670
• NI
  National Institute of Allergy and Infectious Diseases

  Awards: 1P01AI098670-01A1, P01AI098670
• NC
  National Center for Advancing Translational Sciences

  Awards: TL1 TR002531, UL1 TR002529, TL1TR001107