Clinical trials: the mathematics of falling vaccine efficacy with rising disease incidence

M. Gabriela M. Gomes, Stephen B. Gordon, David G. Lalloo

Research output: Contribution to journalComment/debatepeer-review

10 Citations (Scopus)
1 Downloads (Pure)


Reports of unexplained discrepancies in the efficacy of vaccines, as estimated from randomised controlled trials in different parts of the world, are commonplace in the literature [1], [2], [3], [4]. Moreover, there is a consistent trend for lower vaccine efficacy when measured in settings where the disease of interest has a higher incidence, leading to questions about the appropriateness of pooled estimates. Here, we examine the mathematical basis for such trends and propose a measure of efficacy that is valid across settings. The approach relies on fitting mechanistic models, which specify pathogen exposures and host responses, to global vaccine trial data stratified by local disease incidence. Such models enable the estimation of vaccine protection per exposure to the pathogen. A strategy to estimate per-exposure vaccine efficacy will enable more accurate estimates of vaccine efficacy across a range of disease incidence [5].
Original languageEnglish
Pages (from-to)3007-3009
Number of pages3
Issue number27
Early online date10 May 2016
Publication statusPublished - 8 Jun 2016


  • efficacy of vaccines
  • randomised controlled trials
  • vaccine protection per exposure


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