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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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
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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. |
format | Online Article Text |
id | pubmed-6596890 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
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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