Construction of the Design Matrix for Generalized Linear Mixed-Effects Models in the Context of Clinical Trials of Treatment Sequences

The problem of constructing a design matrix of full rank for generalized linear mixed-effects models (GLMMs) has not been addressed in statistical literature in the context of clinical trials of treatment sequences. Solving this problem is important because the most popular estimation methods for GL...

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Autores:
Diaz, Francisco J.
Tipo de recurso:
Article of journal
Fecha de publicación:
2018
Institución:
Universidad Nacional de Colombia
Repositorio:
Universidad Nacional de Colombia
Idioma:
spa
OAI Identifier:
oai:repositorio.unal.edu.co:unal/66485
Acceso en línea:
https://repositorio.unal.edu.co/handle/unal/66485
http://bdigital.unal.edu.co/67513/
Palabra clave:
51 Matemáticas / Mathematics
31 Colecciones de estadística general / Statistics
Augmented regression
robust fixed-effects estimators
generalized least squares
maximum likelihood
quasi-likelihood
random effects linear models
Cuasi-verosimilitud
diseño cruzado
efectos de arrastre
estimabilidad
estimadores robustos de efectos fijos
identificabilidad
inversas generalizadas
matriz de diseño
máxima verosimilitud
mínimos cuadrados generalizados
modelos lineales de efectos
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openAccess
License
Atribución-NoComercial 4.0 Internacional
id UNACIONAL2_810b618acbc8f14b19b475216b0a9e99
oai_identifier_str oai:repositorio.unal.edu.co:unal/66485
network_acronym_str UNACIONAL2
network_name_str Universidad Nacional de Colombia
repository_id_str
dc.title.spa.fl_str_mv Construction of the Design Matrix for Generalized Linear Mixed-Effects Models in the Context of Clinical Trials of Treatment Sequences
title Construction of the Design Matrix for Generalized Linear Mixed-Effects Models in the Context of Clinical Trials of Treatment Sequences
spellingShingle Construction of the Design Matrix for Generalized Linear Mixed-Effects Models in the Context of Clinical Trials of Treatment Sequences
51 Matemáticas / Mathematics
31 Colecciones de estadística general / Statistics
Augmented regression
robust fixed-effects estimators
generalized least squares
maximum likelihood
quasi-likelihood
random effects linear models
Cuasi-verosimilitud
diseño cruzado
efectos de arrastre
estimabilidad
estimadores robustos de efectos fijos
identificabilidad
inversas generalizadas
matriz de diseño
máxima verosimilitud
mínimos cuadrados generalizados
modelos lineales de efectos
title_short Construction of the Design Matrix for Generalized Linear Mixed-Effects Models in the Context of Clinical Trials of Treatment Sequences
title_full Construction of the Design Matrix for Generalized Linear Mixed-Effects Models in the Context of Clinical Trials of Treatment Sequences
title_fullStr Construction of the Design Matrix for Generalized Linear Mixed-Effects Models in the Context of Clinical Trials of Treatment Sequences
title_full_unstemmed Construction of the Design Matrix for Generalized Linear Mixed-Effects Models in the Context of Clinical Trials of Treatment Sequences
title_sort Construction of the Design Matrix for Generalized Linear Mixed-Effects Models in the Context of Clinical Trials of Treatment Sequences
dc.creator.fl_str_mv Diaz, Francisco J.
dc.contributor.author.spa.fl_str_mv Diaz, Francisco J.
dc.subject.ddc.spa.fl_str_mv 51 Matemáticas / Mathematics
31 Colecciones de estadística general / Statistics
topic 51 Matemáticas / Mathematics
31 Colecciones de estadística general / Statistics
Augmented regression
robust fixed-effects estimators
generalized least squares
maximum likelihood
quasi-likelihood
random effects linear models
Cuasi-verosimilitud
diseño cruzado
efectos de arrastre
estimabilidad
estimadores robustos de efectos fijos
identificabilidad
inversas generalizadas
matriz de diseño
máxima verosimilitud
mínimos cuadrados generalizados
modelos lineales de efectos
dc.subject.proposal.spa.fl_str_mv Augmented regression
robust fixed-effects estimators
generalized least squares
maximum likelihood
quasi-likelihood
random effects linear models
Cuasi-verosimilitud
diseño cruzado
efectos de arrastre
estimabilidad
estimadores robustos de efectos fijos
identificabilidad
inversas generalizadas
matriz de diseño
máxima verosimilitud
mínimos cuadrados generalizados
modelos lineales de efectos
description The problem of constructing a design matrix of full rank for generalized linear mixed-effects models (GLMMs) has not been addressed in statistical literature in the context of clinical trials of treatment sequences. Solving this problem is important because the most popular estimation methods for GLMMs assume a design matrix of full rank, and GLMMs are useful tools in statistical practice. We propose new developments in GLMMs that address this problem. We present a new model for the design and analysis of clinical trials of treatment sequences, which utilizes some special sequences called skip sequences. We present a theorem showing that estimators computed through quasi-likelihood, maximum likelihood or generalized least squares, or through robust approaches, exist only if appropriate skip sequences are used. We prove theorems that establish methods for implementing skip sequences in practice. In particular, one of these theorems computes the necessary skip sequences explicitly. Our new approach allows building design matrices of full rank and facilitates the implementation of regression models in the experimental design and data analysis of clinical trials of treatment sequences. We also explain why the standard approach to constructing dummy variables is inappropriate in studies of treatment sequences. The methods are illustrated with a data analysis of the STAR*D study of sequences of treatments for depression.
publishDate 2018
dc.date.issued.spa.fl_str_mv 2018-07-01
dc.date.accessioned.spa.fl_str_mv 2019-07-03T02:13:09Z
dc.date.available.spa.fl_str_mv 2019-07-03T02:13:09Z
dc.type.spa.fl_str_mv Artículo de revista
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.driver.spa.fl_str_mv info:eu-repo/semantics/article
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dc.type.content.spa.fl_str_mv Text
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format http://purl.org/coar/resource_type/c_6501
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dc.identifier.issn.spa.fl_str_mv ISSN: 2389-8976
dc.identifier.uri.none.fl_str_mv https://repositorio.unal.edu.co/handle/unal/66485
dc.identifier.eprints.spa.fl_str_mv http://bdigital.unal.edu.co/67513/
identifier_str_mv ISSN: 2389-8976
url https://repositorio.unal.edu.co/handle/unal/66485
http://bdigital.unal.edu.co/67513/
dc.language.iso.spa.fl_str_mv spa
language spa
dc.relation.spa.fl_str_mv https://revistas.unal.edu.co/index.php/estad/article/view/63332
dc.relation.ispartof.spa.fl_str_mv Universidad Nacional de Colombia Revistas electrónicas UN Revista Colombiana de Estadística
Revista Colombiana de Estadística
dc.relation.references.spa.fl_str_mv Diaz, Francisco J. (2018) Construction of the Design Matrix for Generalized Linear Mixed-Effects Models in the Context of Clinical Trials of Treatment Sequences. Revista Colombiana de Estadística, 41 (2). pp. 191-233. ISSN 2389-8976
dc.rights.spa.fl_str_mv Derechos reservados - Universidad Nacional de Colombia
dc.rights.coar.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.rights.license.spa.fl_str_mv Atribución-NoComercial 4.0 Internacional
dc.rights.uri.spa.fl_str_mv http://creativecommons.org/licenses/by-nc/4.0/
dc.rights.accessrights.spa.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv Atribución-NoComercial 4.0 Internacional
Derechos reservados - Universidad Nacional de Colombia
http://creativecommons.org/licenses/by-nc/4.0/
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.mimetype.spa.fl_str_mv application/pdf
dc.publisher.spa.fl_str_mv Universidad Nacional de Colombia - Sede Bogotá - Facultad de Ciencias - Departamento de Estadística
institution Universidad Nacional de Colombia
bitstream.url.fl_str_mv https://repositorio.unal.edu.co/bitstream/unal/66485/1/63332-390960-1-PB.pdf
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repository.name.fl_str_mv Repositorio Institucional Universidad Nacional de Colombia
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spelling Atribución-NoComercial 4.0 InternacionalDerechos reservados - Universidad Nacional de Colombiahttp://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Diaz, Francisco J.7f6eb4be-0dd4-4828-9bbd-5fd118f995e73002019-07-03T02:13:09Z2019-07-03T02:13:09Z2018-07-01ISSN: 2389-8976https://repositorio.unal.edu.co/handle/unal/66485http://bdigital.unal.edu.co/67513/The problem of constructing a design matrix of full rank for generalized linear mixed-effects models (GLMMs) has not been addressed in statistical literature in the context of clinical trials of treatment sequences. Solving this problem is important because the most popular estimation methods for GLMMs assume a design matrix of full rank, and GLMMs are useful tools in statistical practice. We propose new developments in GLMMs that address this problem. We present a new model for the design and analysis of clinical trials of treatment sequences, which utilizes some special sequences called skip sequences. We present a theorem showing that estimators computed through quasi-likelihood, maximum likelihood or generalized least squares, or through robust approaches, exist only if appropriate skip sequences are used. We prove theorems that establish methods for implementing skip sequences in practice. In particular, one of these theorems computes the necessary skip sequences explicitly. Our new approach allows building design matrices of full rank and facilitates the implementation of regression models in the experimental design and data analysis of clinical trials of treatment sequences. We also explain why the standard approach to constructing dummy variables is inappropriate in studies of treatment sequences. The methods are illustrated with a data analysis of the STAR*D study of sequences of treatments for depression.La estimación de los efectos de arrastre es un problema difícil en el diseño y análisis de ensayos clínicos de secuencias de tratamientos, incluyendo ensayos cruzados. Excepto por diseños simples, estos efectos son usualmente no identificables y, por lo tanto, no estimables. La imposición de restricciones a los parámetros es a menudo no justificada y produce diferentes estimativos de los efectos de arrastre dependiendo de la restricción impuesta. Las inversas generalizadas o el balance de tratamientos a menudo permiten estimar losefectos principales de tratamiento, pero no resuelven el problema de estimar la contribución de los efectos de arrastre de una secuencia de tratamiento. Además, los períodos de lavado no siempre son factibles o éticos. Los diseños con parámetros no identificables comúnmente tienen matrices de diseño que no son de rango completo. Por lo tanto, proponemos métodos para la construcción de matrices de rango completo, sin imponer restricciones artificiales en los efectos de arrastre. Nuestros métodos son aplicables en un contextode modelos lineales mixtos generalizados. Presentamos un nuevo modelo para el diseño y análisis de ensayos clínicos de secuencias de tratamientos, llamado Sistema Anticrónico, e introducimos secuencias de tratamiento especiales llamadas Secuencias de Salto. Demostramos que los efectos de arrastre son identificables sólo si se usan Secuencias de Salto apropiadas. Explicamos cómo implementar en la práctica estas secuencias, y presentamos un método para calcular las secuencias apropiadas. Presentamos aplicaciones al diseño de un estudio cruzado con 3 tratamientos y 3 períodos, y al análisis del estudio STAR*D de secuencias de tratamientos para la depresión.application/pdfspaUniversidad Nacional de Colombia - Sede Bogotá - Facultad de Ciencias - Departamento de Estadísticahttps://revistas.unal.edu.co/index.php/estad/article/view/63332Universidad Nacional de Colombia Revistas electrónicas UN Revista Colombiana de EstadísticaRevista Colombiana de EstadísticaDiaz, Francisco J. (2018) Construction of the Design Matrix for Generalized Linear Mixed-Effects Models in the Context of Clinical Trials of Treatment Sequences. Revista Colombiana de Estadística, 41 (2). pp. 191-233. ISSN 2389-897651 Matemáticas / Mathematics31 Colecciones de estadística general / StatisticsAugmented regressionrobust fixed-effects estimatorsgeneralized least squaresmaximum likelihoodquasi-likelihoodrandom effects linear modelsCuasi-verosimilituddiseño cruzadoefectos de arrastreestimabilidadestimadores robustos de efectos fijosidentificabilidadinversas generalizadasmatriz de diseñomáxima verosimilitudmínimos cuadrados generalizadosmodelos lineales de efectosConstruction of the Design Matrix for Generalized Linear Mixed-Effects Models in the Context of Clinical Trials of Treatment SequencesArtículo de revistainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1http://purl.org/coar/version/c_970fb48d4fbd8a85Texthttp://purl.org/redcol/resource_type/ARTORIGINAL63332-390960-1-PB.pdfapplication/pdf909341https://repositorio.unal.edu.co/bitstream/unal/66485/1/63332-390960-1-PB.pdf2980e65b00bf6db26f7598a848645ca0MD51THUMBNAIL63332-390960-1-PB.pdf.jpg63332-390960-1-PB.pdf.jpgGenerated Thumbnailimage/jpeg6235https://repositorio.unal.edu.co/bitstream/unal/66485/2/63332-390960-1-PB.pdf.jpg70105e07a6e718fb92e99342cfd09656MD52unal/66485oai:repositorio.unal.edu.co:unal/664852023-05-25 23:02:54.063Repositorio Institucional Universidad Nacional de Colombiarepositorio_nal@unal.edu.co