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Developing and testing high-efficacy patient subgroups within a clinical trial using risk scores

There is the potential for high-dimensional information about patients collected in clinical trials (such as genomic, imaging, and data from wearable technologies) to be informative for the efficacy of a new treatment in situations where only a subset of patients benefits from the treatment. The ada...

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Autores principales: Cherlin, Svetlana, Wason, James M.S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611900/
https://www.ncbi.nlm.nih.gov/pubmed/32662542
http://dx.doi.org/10.1002/sim.8665
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author Cherlin, Svetlana
Wason, James M.S.
author_facet Cherlin, Svetlana
Wason, James M.S.
author_sort Cherlin, Svetlana
collection PubMed
description There is the potential for high-dimensional information about patients collected in clinical trials (such as genomic, imaging, and data from wearable technologies) to be informative for the efficacy of a new treatment in situations where only a subset of patients benefits from the treatment. The adaptive signature design (ASD) method has been proposed for developing and testing the efficacy of a treatment in a high-efficacy patient group (the sensitive group) using genetic data. The method requires selection of three tuning parameters which may be highly computationally expensive. We propose a variation to the ASD method, the cross-validated risk scores (CVRS) design method, that does not require selection of any tuning parameters. The method is based on computing a risk score for each patient and dividing them into clusters using a nonparametric clustering procedure.We assess the properties of CVRS against the originally proposed cross-validated ASD using simulation data and a real psychiatry trial. CVRS, as assessed for various sample sizes and response rates, has a substantial reduction in the computational time required. In many simulation scenarios, there is a substantial improvement in the ability to correctly identify the sensitive group and the power of the design to detect a treatment effect in the sensitive group.We illustrate the application of the CVRS method on the psychiatry trial.
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spelling pubmed-76119002021-10-27 Developing and testing high-efficacy patient subgroups within a clinical trial using risk scores Cherlin, Svetlana Wason, James M.S. Stat Med Article There is the potential for high-dimensional information about patients collected in clinical trials (such as genomic, imaging, and data from wearable technologies) to be informative for the efficacy of a new treatment in situations where only a subset of patients benefits from the treatment. The adaptive signature design (ASD) method has been proposed for developing and testing the efficacy of a treatment in a high-efficacy patient group (the sensitive group) using genetic data. The method requires selection of three tuning parameters which may be highly computationally expensive. We propose a variation to the ASD method, the cross-validated risk scores (CVRS) design method, that does not require selection of any tuning parameters. The method is based on computing a risk score for each patient and dividing them into clusters using a nonparametric clustering procedure.We assess the properties of CVRS against the originally proposed cross-validated ASD using simulation data and a real psychiatry trial. CVRS, as assessed for various sample sizes and response rates, has a substantial reduction in the computational time required. In many simulation scenarios, there is a substantial improvement in the ability to correctly identify the sensitive group and the power of the design to detect a treatment effect in the sensitive group.We illustrate the application of the CVRS method on the psychiatry trial. 2020-10-30 2020-07-14 /pmc/articles/PMC7611900/ /pubmed/32662542 http://dx.doi.org/10.1002/sim.8665 Text en https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the Creative Commons Attribution (https://creativecommons.org/licenses/by/4.0/) , which permits use, distribution and reproduction in any medium, provided the original work is properly cited
spellingShingle Article
Cherlin, Svetlana
Wason, James M.S.
Developing and testing high-efficacy patient subgroups within a clinical trial using risk scores
title Developing and testing high-efficacy patient subgroups within a clinical trial using risk scores
title_full Developing and testing high-efficacy patient subgroups within a clinical trial using risk scores
title_fullStr Developing and testing high-efficacy patient subgroups within a clinical trial using risk scores
title_full_unstemmed Developing and testing high-efficacy patient subgroups within a clinical trial using risk scores
title_short Developing and testing high-efficacy patient subgroups within a clinical trial using risk scores
title_sort developing and testing high-efficacy patient subgroups within a clinical trial using risk scores
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611900/
https://www.ncbi.nlm.nih.gov/pubmed/32662542
http://dx.doi.org/10.1002/sim.8665
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