English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Conducting vaccine efficacy trials during outbreaks of emerging pathogens poses particular challenges. The "Ebola ça 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 infection, and we may not know the time required for the vaccinee to develop a protective immune response. As a result, including events observed shortly after vaccination may bias the per protocol estimate of vaccine efficacy. We provide a framework for approximating the bias and power of any given analysis period as functions of the background infection hazard rate, disease incubation period, and vaccine immune response. We use this framework to provide recommendations for designing standard vaccine efficacy trials and trials with a delayed vaccination comparator. Briefly, narrower analysis periods within the correct window can minimize or eliminate bias but may suffer from reduced power. Designs should be reasonably robust to misspecification of the incubation period and time to develop a vaccine immune response.

Design of vaccine trials during outbreaks with and without a delayed vaccination comparator