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Pair Matcher (PaM): fast model-based optimization of treatment/case-control matches

MOTIVATION: In clinical trials, individuals are matched using demographic criteria, paired and then randomly assigned to treatment and control groups to determine a drug’s efficacy. A chief cause for the irreproducibility of results across pilot to Phase-III trials is population stratification bias...

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Detalles Bibliográficos
Autores principales: Elhaik, Eran, Ryan, Desmond M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6596890/
https://www.ncbi.nlm.nih.gov/pubmed/30445488
http://dx.doi.org/10.1093/bioinformatics/bty946
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author Elhaik, Eran
Ryan, Desmond M
author_facet Elhaik, Eran
Ryan, Desmond M
author_sort Elhaik, Eran
collection PubMed
description MOTIVATION: In clinical trials, individuals are matched using demographic criteria, paired and then randomly assigned to treatment and control groups to determine a drug’s efficacy. A chief cause for the irreproducibility of results across pilot to Phase-III trials is population stratification bias caused by the uneven distribution of ancestries in the treatment and control groups. RESULTS: Pair Matcher (PaM) addresses stratification bias by optimizing pairing assignments a priori and/or a posteriori to the trial using both genetic and demographic criteria. Using simulated and real datasets, we show that PaM identifies ideal and near-ideal pairs that are more genetically homogeneous than those identified based on competing methods, including the commonly used principal component analysis (PCA). Homogenizing the treatment (or case) and control groups can be expected to improve the accuracy and reproducibility of the trial or genetic study. PaM’s ancestral inferences also allow characterizing responders and developing a precision medicine approach to treatment. AVAILABILITY AND IMPLEMENTATION: PaM is freely available via Rhttps://github.com/eelhaik/PAM and a web-interface at http://elhaik-matcher.sheffield.ac.uk/ElhaikLab/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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spelling pubmed-65968902019-07-03 Pair Matcher (PaM): fast model-based optimization of treatment/case-control matches Elhaik, Eran Ryan, Desmond M Bioinformatics Original Papers MOTIVATION: In clinical trials, individuals are matched using demographic criteria, paired and then randomly assigned to treatment and control groups to determine a drug’s efficacy. A chief cause for the irreproducibility of results across pilot to Phase-III trials is population stratification bias caused by the uneven distribution of ancestries in the treatment and control groups. RESULTS: Pair Matcher (PaM) addresses stratification bias by optimizing pairing assignments a priori and/or a posteriori to the trial using both genetic and demographic criteria. Using simulated and real datasets, we show that PaM identifies ideal and near-ideal pairs that are more genetically homogeneous than those identified based on competing methods, including the commonly used principal component analysis (PCA). Homogenizing the treatment (or case) and control groups can be expected to improve the accuracy and reproducibility of the trial or genetic study. PaM’s ancestral inferences also allow characterizing responders and developing a precision medicine approach to treatment. AVAILABILITY AND IMPLEMENTATION: PaM is freely available via Rhttps://github.com/eelhaik/PAM and a web-interface at http://elhaik-matcher.sheffield.ac.uk/ElhaikLab/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. Oxford University Press 2019-07-01 2018-11-16 /pmc/articles/PMC6596890/ /pubmed/30445488 http://dx.doi.org/10.1093/bioinformatics/bty946 Text en © The Author(s) 2018. Published by Oxford University Press. 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 reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Papers
Elhaik, Eran
Ryan, Desmond M
Pair Matcher (PaM): fast model-based optimization of treatment/case-control matches
title Pair Matcher (PaM): fast model-based optimization of treatment/case-control matches
title_full Pair Matcher (PaM): fast model-based optimization of treatment/case-control matches
title_fullStr Pair Matcher (PaM): fast model-based optimization of treatment/case-control matches
title_full_unstemmed Pair Matcher (PaM): fast model-based optimization of treatment/case-control matches
title_short Pair Matcher (PaM): fast model-based optimization of treatment/case-control matches
title_sort pair matcher (pam): fast model-based optimization of treatment/case-control matches
topic Original Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6596890/
https://www.ncbi.nlm.nih.gov/pubmed/30445488
http://dx.doi.org/10.1093/bioinformatics/bty946
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