A platform trial design for preventive vaccines against Marburg virus and other emerging infectious disease threats
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Published version
Author(s)
Type
Journal Article
Abstract
Background: The threat of a possible Marburg virus disease outbreak in Central and Western Africa is growing. While no Marburg virus vaccines are currently available for use, several candidates are in the pipeline. Building on knowledge and experiences in the designs of vaccine efficacy trials against other pathogens including SARS-CoV-2, we develop designs of randomized phase 3 vaccine efficacy trials for Marburg virus vaccines. Methods: A core protocol approach will be used, allowing multiple vaccine candidates to be tested against controls. The primary objective of the trial will be to evaluate the effect of each vaccine on the rate of virologically confirmed Marburg virus disease, although Marburg infection, assessed via seroconversion could be the primary objective in some cases. The overall trial design will be a mixture of individually and cluster randomized designs, with individual randomization done whenever possible. Clusters will consist of either contacts and contacts of contacts of index cases, i.e., ring vaccination, or other transmission units. Results: The primary efficacy endpoint will be analysed as a time-to-event outcome. A vaccine will be considered successful if its estimated efficacy is greater than 50% and has sufficient precision to rule out that true efficacy is less than 30%. This will require approximately 150 total endpoints, i.e., cases of confirmed Marburg virus disease, per vaccine/comparator combination Interim analyses will be conducted after 50 and after 100 events. Statistical analysis of the trial will be blended across the different types of designs. Under the assumption of a 6-month attack rate of 1% of the of the participants in the placebo arm for both the individually and cluster randomize populations, the most likely sample size is about 20,000 participants per arm Conclusions: This event-driven design takes into the account the potentially sporadic spread of Marburg virus. The proposed trial design may be applicable for other pathogens against which effective vaccines are not yet available.
Date Issued
2022-12-01
Date Acceptance
2022-05-24
ISSN
1740-7745
Publisher
SAGE Publications
Start Page
647
End Page
654
Journal / Book Title
Clinical Trials
Volume
19
Issue
6
Copyright Statement
© The Author(s) 2022. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
License URI
Sponsor
Medical Research Council (MRC)
National Institute for Health Research
Grant Number
MR/R015600/1
EPIDZO34
Subjects
Science & Technology
Life Sciences & Biomedicine
Medicine, Research & Experimental
Research & Experimental Medicine
Randomized placebo-controlled vaccine trial
cluster-randomized vaccine trial
Marburg virus
vaccine efficacy
emerging infectious disease threat
CLUSTER-RANDOMIZED-TRIALS
CLINICAL-TRIALS
SAMPLE-SIZE
EVENT
TIME
Marburg virus
Randomized placebo-controlled vaccine trial
cluster-randomized vaccine trial
emerging infectious disease threat
vaccine efficacy
Animals
Humans
Communicable Diseases, Emerging
COVID-19
Marburg Virus Disease
Marburgvirus
SARS-CoV-2
Vaccines
Animals
Humans
Communicable Diseases, Emerging
Marburg Virus Disease
Vaccines
Marburgvirus
COVID-19
SARS-CoV-2
Statistics & Probability
0104 Statistics
1103 Clinical Sciences
Publication Status
Published
Date Publish Online
2022-07-22