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Leaky Vaccines Protect Highly Exposed Recipients at a Lower Rate: Implications for Vaccine Efficacy Estimation and Sieve Analysis

“Leaky” vaccines are those for which vaccine-induced protection reduces infection rates on a per-exposure basis, as opposed to “all-or-none” vaccines, which reduce infection rates to zero for some fraction of subjects, independent of the number of exposures. Leaky vaccines therefore protect subjects...

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Autor principal: Edlefsen, Paul T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033482/
https://www.ncbi.nlm.nih.gov/pubmed/24895500
http://dx.doi.org/10.1155/2014/813789
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author Edlefsen, Paul T.
author_facet Edlefsen, Paul T.
author_sort Edlefsen, Paul T.
collection PubMed
description “Leaky” vaccines are those for which vaccine-induced protection reduces infection rates on a per-exposure basis, as opposed to “all-or-none” vaccines, which reduce infection rates to zero for some fraction of subjects, independent of the number of exposures. Leaky vaccines therefore protect subjects with fewer exposures at a higher effective rate than subjects with more exposures. This simple observation has serious implications for analysis methodologies that rely on the assumption that the vaccine effect is homogeneous across subjects. We argue and show through examples that this heterogeneous vaccine effect leads to a violation of the proportional hazards assumption, to incomparability of infected cases across treatment groups, and to nonindependence of the distributions of the competing failure processes in a competing risks setting. We discuss implications for vaccine efficacy estimation, correlates of protection analysis, and mark-specific efficacy analysis (also known as sieve analysis).
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spelling pubmed-40334822014-06-03 Leaky Vaccines Protect Highly Exposed Recipients at a Lower Rate: Implications for Vaccine Efficacy Estimation and Sieve Analysis Edlefsen, Paul T. Comput Math Methods Med Research Article “Leaky” vaccines are those for which vaccine-induced protection reduces infection rates on a per-exposure basis, as opposed to “all-or-none” vaccines, which reduce infection rates to zero for some fraction of subjects, independent of the number of exposures. Leaky vaccines therefore protect subjects with fewer exposures at a higher effective rate than subjects with more exposures. This simple observation has serious implications for analysis methodologies that rely on the assumption that the vaccine effect is homogeneous across subjects. We argue and show through examples that this heterogeneous vaccine effect leads to a violation of the proportional hazards assumption, to incomparability of infected cases across treatment groups, and to nonindependence of the distributions of the competing failure processes in a competing risks setting. We discuss implications for vaccine efficacy estimation, correlates of protection analysis, and mark-specific efficacy analysis (also known as sieve analysis). Hindawi Publishing Corporation 2014 2014-05-07 /pmc/articles/PMC4033482/ /pubmed/24895500 http://dx.doi.org/10.1155/2014/813789 Text en Copyright © 2014 Paul T. Edlefsen. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Edlefsen, Paul T.
Leaky Vaccines Protect Highly Exposed Recipients at a Lower Rate: Implications for Vaccine Efficacy Estimation and Sieve Analysis
title Leaky Vaccines Protect Highly Exposed Recipients at a Lower Rate: Implications for Vaccine Efficacy Estimation and Sieve Analysis
title_full Leaky Vaccines Protect Highly Exposed Recipients at a Lower Rate: Implications for Vaccine Efficacy Estimation and Sieve Analysis
title_fullStr Leaky Vaccines Protect Highly Exposed Recipients at a Lower Rate: Implications for Vaccine Efficacy Estimation and Sieve Analysis
title_full_unstemmed Leaky Vaccines Protect Highly Exposed Recipients at a Lower Rate: Implications for Vaccine Efficacy Estimation and Sieve Analysis
title_short Leaky Vaccines Protect Highly Exposed Recipients at a Lower Rate: Implications for Vaccine Efficacy Estimation and Sieve Analysis
title_sort leaky vaccines protect highly exposed recipients at a lower rate: implications for vaccine efficacy estimation and sieve analysis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033482/
https://www.ncbi.nlm.nih.gov/pubmed/24895500
http://dx.doi.org/10.1155/2014/813789
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