phase1RMD: An R package for repeated measures dose-finding designs with novel toxicity and efficacy endpoints.

Traditional dose-finding designs are substantially inefficient for targeted agents and cancer immunotherapies by failing to incorporate efficacy signals, mild and moderate adverse events, and late, cumulative toxicities. However, the lack of user-friendly software is a barrier to the practical use o...

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Autores principales:	Jun Yin, Yu Du, Rui Qin, Shihao Shen, Sumithra Mandrekar
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ede96bfb61504b40971bf634b5050716
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spelling	oai:doaj.org-article:ede96bfb61504b40971bf634b50507162021-12-02T20:08:39Zphase1RMD: An R package for repeated measures dose-finding designs with novel toxicity and efficacy endpoints.1932-620310.1371/journal.pone.0256391https://doaj.org/article/ede96bfb61504b40971bf634b50507162021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0256391https://doaj.org/toc/1932-6203Traditional dose-finding designs are substantially inefficient for targeted agents and cancer immunotherapies by failing to incorporate efficacy signals, mild and moderate adverse events, and late, cumulative toxicities. However, the lack of user-friendly software is a barrier to the practical use of the novel phase I designs, despite their demonstrated superiority of traditional 3+3 designs. To overcome these barriers, we present an R package, phase1RMD, which provides a comprehensive implementation of novel designs with repeated toxicity measures and early efficacy. A novel phase I repeated measures design that used a continuous toxicity score from multiple treatment cycles was implemented. Furthermore, in studies where preliminary efficacy is evaluated, an adaptive, multi-stage design to identify the most efficacious dose with acceptable toxicity was demonstrated. Functions are provided to recommend the next dose based on the data collected in a phase I trial, as well as to assess trial characteristics given design parameters via simulations. The repeated measure designs accurately estimated both the magnitude and direction of toxicity trends in late treatment cycles, and allocated more patients at therapeutic doses. The R package for implementing these designs is available from the Comprehensive R Archive Network. To our best knowledge, this is the first software that implement novel phase I dose-finding designs that simultaneously accounts for the multiple-grade toxicity events over multiple treatment cycles and a continuous early efficacy outcome. With the software published on CRAN, we will pursue the implementation of these designs in phase I trials in real-life settings.Jun YinYu DuRui QinShihao ShenSumithra MandrekarPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0256391 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jun Yin Yu Du Rui Qin Shihao Shen Sumithra Mandrekar phase1RMD: An R package for repeated measures dose-finding designs with novel toxicity and efficacy endpoints.
description	Traditional dose-finding designs are substantially inefficient for targeted agents and cancer immunotherapies by failing to incorporate efficacy signals, mild and moderate adverse events, and late, cumulative toxicities. However, the lack of user-friendly software is a barrier to the practical use of the novel phase I designs, despite their demonstrated superiority of traditional 3+3 designs. To overcome these barriers, we present an R package, phase1RMD, which provides a comprehensive implementation of novel designs with repeated toxicity measures and early efficacy. A novel phase I repeated measures design that used a continuous toxicity score from multiple treatment cycles was implemented. Furthermore, in studies where preliminary efficacy is evaluated, an adaptive, multi-stage design to identify the most efficacious dose with acceptable toxicity was demonstrated. Functions are provided to recommend the next dose based on the data collected in a phase I trial, as well as to assess trial characteristics given design parameters via simulations. The repeated measure designs accurately estimated both the magnitude and direction of toxicity trends in late treatment cycles, and allocated more patients at therapeutic doses. The R package for implementing these designs is available from the Comprehensive R Archive Network. To our best knowledge, this is the first software that implement novel phase I dose-finding designs that simultaneously accounts for the multiple-grade toxicity events over multiple treatment cycles and a continuous early efficacy outcome. With the software published on CRAN, we will pursue the implementation of these designs in phase I trials in real-life settings.
format	article
author	Jun Yin Yu Du Rui Qin Shihao Shen Sumithra Mandrekar
author_facet	Jun Yin Yu Du Rui Qin Shihao Shen Sumithra Mandrekar
author_sort	Jun Yin
title	phase1RMD: An R package for repeated measures dose-finding designs with novel toxicity and efficacy endpoints.
title_short	phase1RMD: An R package for repeated measures dose-finding designs with novel toxicity and efficacy endpoints.
title_full	phase1RMD: An R package for repeated measures dose-finding designs with novel toxicity and efficacy endpoints.
title_fullStr	phase1RMD: An R package for repeated measures dose-finding designs with novel toxicity and efficacy endpoints.
title_full_unstemmed	phase1RMD: An R package for repeated measures dose-finding designs with novel toxicity and efficacy endpoints.
title_sort	phase1rmd: an r package for repeated measures dose-finding designs with novel toxicity and efficacy endpoints.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/ede96bfb61504b40971bf634b5050716
work_keys_str_mv	AT junyin phase1rmdanrpackageforrepeatedmeasuresdosefindingdesignswithnoveltoxicityandefficacyendpoints AT yudu phase1rmdanrpackageforrepeatedmeasuresdosefindingdesignswithnoveltoxicityandefficacyendpoints AT ruiqin phase1rmdanrpackageforrepeatedmeasuresdosefindingdesignswithnoveltoxicityandefficacyendpoints AT shihaoshen phase1rmdanrpackageforrepeatedmeasuresdosefindingdesignswithnoveltoxicityandefficacyendpoints AT sumithramandrekar phase1rmdanrpackageforrepeatedmeasuresdosefindingdesignswithnoveltoxicityandefficacyendpoints
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phase1RMD: An R package for repeated measures dose-finding designs with novel toxicity and efficacy endpoints.

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