Evidence map›Paper›PMID 35866633›Full record

ArticleClinical trials (London, England)2022

A platform trial design for preventive vaccines against Marburg virus and other emerging infectious disease threats.

Ira M Longini, Yang Yang, Thomas R Fleming, César Muñoz-Fontela, Rui Wang, Susan S Ellenberg, George Qian, M Elizabeth Halloran, Martha Nason, Victor De Gruttola and 4 more

Open access · hybridAbstract readClinical Trial Protocol
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical trials (London, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.3field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
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  4. Designs for Vaccine Studies.Annual review of statistics and its application · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 10 institutions in 5 countries.

Ira M LonginiDepartment of Biostatistics, University of Florida, Gainesville, FL, USA.ORCID 0000-0002-2780-9382
Yang YangDepartment of Biostatistics, University of Florida, Gainesville, FL, USA.
Thomas R FlemingDepartment of Biostatistics, University of Washington, Seattle, WA, USA.ORCID 0000-0002-0420-5068
César Muñoz-FontelaBernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany.
Rui WangDepartment of Population Medicine, Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, MA, USA.
Susan S EllenbergDepartment of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-2364-5253
George QianLondon School of Hygiene & Tropical Medicine, London, UK.
M Elizabeth HalloranDepartment of Biostatistics, University of Washington, Seattle, WA, USA.
Martha NasonBiostatistics Research Branch, National Institute of Allergy and Infectious Diseases (NIAID/NIH), Bethesda, MD, USA.
Victor De GruttolaDepartment of Biostatistics, Harvard University, Boston, MA, USA.ORCID 0000-0003-2772-6242
Sabue MulanguInstitut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo.
Yunda HuangLondon School of Hygiene & Tropical Medicine, London, UK.
Christl A DonnellyDepartment of Statistics, University of Oxford, Oxford, UK.
Ana-Maria Henao RestrepoWorld Health Organization, Geneva, Switzerland.
Harvard University · USLondon School of Hygiene & Tropical Medicine · GBUniversity of Florida · USUniversity of Washington · USGerman Center for Infection Research · DENational Institute of Allergy and Infectious Diseases · USNational Institute of Biomedical Research · CDUniversity of Oxford · GBUniversity of Pennsylvania · USWorld Health Organization · CH

Funding

STATISTICAL ISSUES IN AIDS RESEARCHR37AI029168 · NIAID · UNIVERSITY OF WASHINGTON · PI JAMES P HUGHES · 1999 to 2026
$9.8M
Design and Analysis of Vaccine Trials for Emerging Infectious Disease ThreatsR01AI139761 · NIAID · UNIVERSITY OF FLORIDA · PI DEAN, NATALIE EXNER · 2018 to 2022
$3.6M
Mathematical and Statistical Methods for the Control of Global Infectious Disease ThreatsR56AI148284 · NIAID · UNIVERSITY OF FLORIDA · PI HALLORAN, M ELIZABETH, LONGINI, IRA M · 2020 to 2020
$802k
Network modeling and robust estimation of the intraclass correlation coefficient to inform the design and analysis of cluster randomized trials for infectious diseasesR01AI136947 · NIAID · HARVARD PILGRIM HEALTH CARE, INC. · PI WANG, RUI · 2018 to 2020
$759k
Medical Research Council MR/R015600/1NIAID NIH HHS R01 AI136947NIAID NIH HHS R01 AI139761NIAID NIH HHS R37 AI029168NIAID NIH HHS R56 AI148284World Health Organization 001
6 · The paper itself

Abstract

backgroundThe 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.

methodsA 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, that is, ring vaccination, or other transmission units.

resultsThe 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, that is, 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 participants in the placebo arm for both the individually and cluster-randomized populations, the most likely sample size is about 20,000 participants per arm.

conclusionThis 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.

Indexed as

Communicable Diseases, EmergingCOVID-19MarburgvirusMarburg Virus DiseaseVaccinesAdaptive Clinical Trials as TopicAnimalsClinical Trials, Phase III as TopicHumansRandomized Controlled Trials as TopicSARS-CoV-2Vaccinescluster-randomized vaccine trialemerging infectious disease threatMarburg virusRandomized placebo-controlled vaccine trialvaccine efficacy

Identifiers

PMID35866633
PMCPMC9679315
OpenAlexW4286717207

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.