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In response to the epidemic, development of a heterologous prime-boost vaccine regimen was accelerated and involved preparation of a phase 3 effectiveness study. While individually randomized controlled trials are widely acknowledged as the gold standard for demonstrating the efficacy of a candidate vaccine, there was considerable debate on the ethical appropriateness of these designs in the context of an epidemic. A suitable phase 3 trial must convincingly ensure unbiased evaluation with sufficient statistical power. In addition, efficient evaluation of a vaccine candidate is required so that an effective vaccine can be immediately disseminated. This manuscript aims to present the statistical and modeling considerations, design rationale and challenges encountered due to the emergent, epidemic setting that led to the selection of a cluster-randomized phase 3 study design under field conditions.<\/jats:p>","DOI":"10.1177\/1740774515621059","type":"journal-article","created":{"date-parts":[[2016,1,15]],"date-time":"2016-01-15T07:02:37Z","timestamp":1452841357000},"page":"57-65","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Simulation-guided phase 3 trial design to evaluate vaccine effectiveness to prevent Ebola virus disease infection: Statistical considerations, design rationale, and challenges"],"prefix":"10.1177","volume":"13","author":[{"given":"An","family":"Vandebosch","sequence":"first","affiliation":[{"name":"Janssen Research & Development, Beerse, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin","family":"Mogg","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, LLC, Spring House, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nele","family":"Goeyvaerts","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, Beerse, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Truyers","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, Beerse, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Greenwood","sequence":"additional","affiliation":[{"name":"London School of Hygiene & Tropical Medicine, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debby","family":"Watson-Jones","sequence":"additional","affiliation":[{"name":"London School of Hygiene & Tropical Medicine, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillermo","family":"Herrera-Taracena","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, LLC, Horsham, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wim","family":"Parys","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, Beerse, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tony","family":"Vangeneugden","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, Beerse, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2016,1,14]]},"reference":[{"key":"bibr1-1740774515621059","unstructured":"World Health Organization (WHO). 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