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The Power of Malaria Vaccine Trials Using Controlled Human Malaria Infection
Controlled human malaria infection (CHMI) in healthy human volunteers is an important and powerful tool in clinical malaria vaccine development. However, power calculations are essential to obtain meaningful estimates of protective efficacy, while minimizing the risk of adverse events. To optimize p...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5230743/ https://www.ncbi.nlm.nih.gov/pubmed/28081133 http://dx.doi.org/10.1371/journal.pcbi.1005255 |
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author | Coffeng, Luc E. Hermsen, Cornelus C. Sauerwein, Robert W. de Vlas, Sake J. |
author_facet | Coffeng, Luc E. Hermsen, Cornelus C. Sauerwein, Robert W. de Vlas, Sake J. |
author_sort | Coffeng, Luc E. |
collection | PubMed |
description | Controlled human malaria infection (CHMI) in healthy human volunteers is an important and powerful tool in clinical malaria vaccine development. However, power calculations are essential to obtain meaningful estimates of protective efficacy, while minimizing the risk of adverse events. To optimize power calculations for CHMI-based malaria vaccine trials, we developed a novel non-linear statistical model for parasite kinetics as measured by qPCR, using data from mosquito-based CHMI experiments in 57 individuals. We robustly account for important sources of variation between and within individuals using a Bayesian framework. Study power is most dependent on the number of individuals in each treatment arm; inter-individual variation in vaccine efficacy and the number of blood samples taken per day matter relatively little. Due to high inter-individual variation in the number of first-generation parasites, hepatic vaccine trials required significantly more study subjects than erythrocytic vaccine trials. We provide power calculations for hypothetical malaria vaccine trials of various designs and conclude that so far, power calculations have been overly optimistic. We further illustrate how upcoming techniques like needle-injected CHMI may reduce required sample sizes. |
format | Online Article Text |
id | pubmed-5230743 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-52307432017-01-31 The Power of Malaria Vaccine Trials Using Controlled Human Malaria Infection Coffeng, Luc E. Hermsen, Cornelus C. Sauerwein, Robert W. de Vlas, Sake J. PLoS Comput Biol Research Article Controlled human malaria infection (CHMI) in healthy human volunteers is an important and powerful tool in clinical malaria vaccine development. However, power calculations are essential to obtain meaningful estimates of protective efficacy, while minimizing the risk of adverse events. To optimize power calculations for CHMI-based malaria vaccine trials, we developed a novel non-linear statistical model for parasite kinetics as measured by qPCR, using data from mosquito-based CHMI experiments in 57 individuals. We robustly account for important sources of variation between and within individuals using a Bayesian framework. Study power is most dependent on the number of individuals in each treatment arm; inter-individual variation in vaccine efficacy and the number of blood samples taken per day matter relatively little. Due to high inter-individual variation in the number of first-generation parasites, hepatic vaccine trials required significantly more study subjects than erythrocytic vaccine trials. We provide power calculations for hypothetical malaria vaccine trials of various designs and conclude that so far, power calculations have been overly optimistic. We further illustrate how upcoming techniques like needle-injected CHMI may reduce required sample sizes. Public Library of Science 2017-01-12 /pmc/articles/PMC5230743/ /pubmed/28081133 http://dx.doi.org/10.1371/journal.pcbi.1005255 Text en © 2017 Coffeng et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Coffeng, Luc E. Hermsen, Cornelus C. Sauerwein, Robert W. de Vlas, Sake J. The Power of Malaria Vaccine Trials Using Controlled Human Malaria Infection |
title | The Power of Malaria Vaccine Trials Using Controlled Human Malaria Infection |
title_full | The Power of Malaria Vaccine Trials Using Controlled Human Malaria Infection |
title_fullStr | The Power of Malaria Vaccine Trials Using Controlled Human Malaria Infection |
title_full_unstemmed | The Power of Malaria Vaccine Trials Using Controlled Human Malaria Infection |
title_short | The Power of Malaria Vaccine Trials Using Controlled Human Malaria Infection |
title_sort | power of malaria vaccine trials using controlled human malaria infection |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5230743/ https://www.ncbi.nlm.nih.gov/pubmed/28081133 http://dx.doi.org/10.1371/journal.pcbi.1005255 |
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