Changes in the primary outcome in Ebola vaccine trial.

Abstract

We read with interest Ana Maria Henao-Restrepo and colleagues' Article (Aug 3, p 857)1Henao-Restrepo AM Longini IM Egger M et al.Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial.Lancet. 2015; 386: 857-866Summary Full Text Full Text PDF PubMed Scopus (595) Google Scholar on the ring vaccination trial of an rVSV-vectored vaccine for Ebola virus disease. This trial represents a fantastic effort in a very short space of time and in challenging circumstances. WHO sponsored the trial, offering the opportunity to show best practices in the design, conduct, and reporting of trials.2World Health OrganizationWHO statement on public disclosure of clinical trial results.http://www.who.int/ictrp/results/enDate: 2015Google Scholar The authors published their study protocol in the British Medical Journal in July, 2015.3Ebola Ça Suffit Ring Vaccination Trial ConsortiumThe ring vaccination trial: a novel cluster randomised controlled trial design to evaluate vaccine efficacy and effectiveness during outbreaks, with special reference to Ebola.BMJ. 2015; 351: h3740PubMed Google Scholar In that report, the primary analysis for vaccine efficacy was described as a comparison of outcomes in the individuals randomly assigned to immediate vaccination compared with those randomly assigned to delayed vaccination. The protocol was not explicit about how non-consent or dropout would be addressed in the analysis. In the preliminary report in The Lancet, the primary analysis of vaccine efficacy differed from this prespecified plan. Specifically, the prespecified plan for the primary analysis of vaccine efficacy would have been a comparison of the 2014 individuals randomly assigned to immediate vaccination with 1498 individuals randomly assigned to delayed vaccination.1Henao-Restrepo AM Longini IM Egger M et al.Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial.Lancet. 2015; 386: 857-866Summary Full Text Full Text PDF PubMed Scopus (595) Google Scholar Whereas the preliminary report described the primary analysis of vaccine efficacy as a comparison of 2014 individuals who actually received immediate vaccination with 2380 who were eligible for delayed vaccination regardless of whether or not they received it. The prespecified primary analysis of vaccine efficacy was not reported and the new primary analysis of vaccine efficacy appeared to be statistically significant with a p value of 0·0036, although actually this finding did not meet the O'Brien-Fleming threshold for the interim analysis of p<0·027.4Krause PR Interim results from a phase 3 Ebola vaccine study in Guinea.Lancet. 2015; 386: 831-833Summary Full Text Full Text PDF PubMed Scopus (21) Google Scholar BJC received grants from National Institute of Allergy and Infectious Diseases, Health and Medical Research Fund from the Government of the Hong Kong Special Administrative Region, and the Harvard Center for Communicable Disease Dynamics from the National Institute of General Medical Sciences. All other authors declare no competing interests. Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trialThe results of this interim analysis indicate that rVSV-ZEBOV might be highly efficacious and safe in preventing Ebola virus disease, and is most likely effective at the population level when delivered during an Ebola virus disease outbreak via a ring vaccination strategy. Full-Text PDF Changes in the primary outcome in Ebola vaccine trial – Authors' replyWe thank Yanyu Zhang and colleagues for their interest in the methods of Ebola ça suffit ring vaccination trial in Guinea1,2 and for their words of encouragement. Full-Text PDF