Design of Vaccine Trials during Outbreaks with and without a Delayed Vaccination Comparator

Conducting vaccine efficacy trials during outbreaks of emerging pathogens poses particular challenges. The Ebola ca suffit trial in Guinea used a novel ring vaccination cluster randomized design to target populations at highest risk of infection. Another key feature of the trial was the use of a delayed vaccination arm as a comparator, in which clusters were randomized to immediate vaccination or vaccination 21 days later. This approach, chosen to improve ethical acceptability of the trial, complicates the statistical analysis as participants in the comparison arm are eventually protected by vaccine. Furthermore, for infectious diseases, we observe time of illness onset and not time of infec