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

被引：11

作者：

Longini, Ira M. ^{[1
]}

Yang, Yang ^{[1
]}

Fleming, Thomas R. ^{[2
]}

Munoz-Fontela, Cesar ^{[3
,4
]}

Wang, Rui ^{[5
,6
,7
]}

Ellenberg, Susan S. ^{[8
]}

Qian, George ^{[9
]}

Halloran, M. Elizabeth ^{[2
,10
]}

Nason, Martha ^{[11
]}

De Gruttola, Victor ^{[7
]}

Mulangu, Sabue ^{[12
]}

Huang, Yunda ^{[9
]}

Donnelly, Christl A. ^{[13
,14
]}

Restrepo, Ana-Maria Henao ^{[15
]}

机构：

[1] Univ Florida, Dept Biostat, Gainesville, FL 32611 USA

[2] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[3] Bernhard Nocht Inst Trop Med, Hamburg, Germany

[4] DZIF, German Ctr Infect Res, Partner Site Hamburg, Hamburg, Germany

[5] Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA

[6] Harvard Med Sch, Boston, MA 02115 USA

[7] Harvard Univ, Dept Biostat, Boston, MA 02115 USA

[8] Univ Penn, Dept Biostat Epidemiol & Informat, Philadelphia, PA 19104 USA

[9] London Sch Hyg & Trop Med, London, England

[10] Fred Hutchinson Canc Ctr, Vaccine & Infect Dis Div, Seattle, WA USA

[11] NIAID, Biostat Res Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[12] Inst Natl Rech Biomed, Kinshasa, DEM REP CONGO

[13] Univ Oxford, Dept Stat, Oxford, England

[14] Imperial Coll London, Dept Infect Dis Epidemiol, London, England

[15] World Hlth Org, Ave Appia 20, CH-1211 Geneva 27, Switzerland

来源：

CLINICAL TRIALS | 2022年 / 19卷 / 06期

基金：

美国国家卫生研究院;

关键词：

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;

D O I：

10.1177/17407745221110880

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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, that is, 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, 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. Conclusion: 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.

引用

页码：647 / 654

页数：8