Solutions to the monotone likelihood in the standard mixture Cure fraction model

Detalhes bibliográficos
Ano de defesa: 2021
Autor(a) principal: Frederico Machado Almeida
Orientador(a): Não Informado pela instituição
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: eng
Instituição de defesa: Universidade Federal de Minas Gerais
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: https://hdl.handle.net/1843/38020
Resumo: Survival models for situations where some individuals are long-term survivors, immune or non-susceptible to the event of interest are extensively studied in biomedical research. Fitting a regression can be problematic in situations involving small sample sizes with many censored times, since the maximum likelihood estimates of some coefficients may be infinity. This phenomenon is commonly known as Monotone Likelihood (ML), occurring in the presence of many categorical and unbalanced covariates. A well-known solution is an adaptation of the Firth's method, originally created to reduce the maximum likelihood estimation bias. The method ensures finite estimates by penalizing the likelihood function, where the penalty term might be interpreted as the Jeffreys invariant prior, largely used in the Bayesian framework. The ML issue in the context involving mixture cure models is a topic rarely discussed in the literature, and it configures a central contribution of this work. In order to handle this point in such context, we propose to derive the adjusted score function based on the Firth method. The second major contribution is to investigate other flexible penalty functions (prior distributions), in which all inference procedures will be based on the posterior samples. An extensive Monte Carlo simulation study indicates good inference performance for the penalized estimates, especially in the Bayesian framework. The analysis is illustrated through a real application involving patients with melanoma assisted at the Hospital das Clínicas/UFMG. This is a relatively novel data set affected by the monotone likelihood issue and containing cured individuals.
id UFMG_f2a8ab8f5783a00aee6d150e2f2dd5ef
oai_identifier_str oai:repositorio.ufmg.br:1843/38020
network_acronym_str UFMG
network_name_str Repositório Institucional da UFMG
repository_id_str
spelling 2021-09-14T21:39:26Z2025-09-09T00:12:11Z2021-09-14T21:39:26Z2021-07-01https://hdl.handle.net/1843/38020Survival models for situations where some individuals are long-term survivors, immune or non-susceptible to the event of interest are extensively studied in biomedical research. Fitting a regression can be problematic in situations involving small sample sizes with many censored times, since the maximum likelihood estimates of some coefficients may be infinity. This phenomenon is commonly known as Monotone Likelihood (ML), occurring in the presence of many categorical and unbalanced covariates. A well-known solution is an adaptation of the Firth's method, originally created to reduce the maximum likelihood estimation bias. The method ensures finite estimates by penalizing the likelihood function, where the penalty term might be interpreted as the Jeffreys invariant prior, largely used in the Bayesian framework. The ML issue in the context involving mixture cure models is a topic rarely discussed in the literature, and it configures a central contribution of this work. In order to handle this point in such context, we propose to derive the adjusted score function based on the Firth method. The second major contribution is to investigate other flexible penalty functions (prior distributions), in which all inference procedures will be based on the posterior samples. An extensive Monte Carlo simulation study indicates good inference performance for the penalized estimates, especially in the Bayesian framework. The analysis is illustrated through a real application involving patients with melanoma assisted at the Hospital das Clínicas/UFMG. This is a relatively novel data set affected by the monotone likelihood issue and containing cured individuals.CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorengUniversidade Federal de Minas Geraishttp://creativecommons.org/licenses/by-nd/3.0/pt/info:eu-repo/semantics/openAccessCure rate modelsEM algorithmFirth methodBayesian inferenceLogistic link functionMelanomaEstatística – TesesVerossimilhança (Estatistica) - TesesEstatística matemática – TesesInferência (Estatística) – TesesMelanona - TesesSolutions to the monotone likelihood in the standard mixture Cure fraction modelSoluções para o problema da verossimilhança monótona no modelo de fração de Curainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisFrederico Machado Almeidareponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGhttp://lattes.cnpq.br/4486716856546664Enrico Antônio Colosimohttp://lattes.cnpq.br/8074052644801438Vinícius Diniz MayrinkVera Lúcia DamascenoTomazellaMário de Castro Filho AndradeFábio Nogueira DamarquiWagner Barreto SouzaModelos de sobrevivência para dados com fração de curados, são frequentes em pesquisas biomédicas. Em situações envolvendo eventos raros, onde é comum obter amostras pequenas com muitos tempos de censura, o processo de estimação dos coeficientes de regressão pode ser problemático, uma vez que algumas estimativas podem não assumir valores finitos. Este fenômeno é conhecido na literatura como o problema da Verosimilhança Monótona (VM), ocorrendo na presença de covariáveis categóricas fortemente desbalanceadas. A solução mais conhecida, é uma adaptação do método de Firth originalmente proposto para reduzir o viés dos estimadores de máxima verossimilhança. O método garante a obtenção de estimativas finitas a partir da penalização da função de verossimilhança, na qual o termo de penalidade pode ser interpretado como sendo a distribuição a priori invariante de Jeffreys, frequentemente usada em inferência Bayesiana. Estudos investigando a VM nos modelos de sobrevivência com fração de curados são escassos. Para solucionar o problema, nossa primeira proposta consiste em derivar a função escore modificada baseando-se no método de Firth. Nossa segunda contribuição consiste em investigar outras funções de penalidade (ou distribuições a priori) baseadas no enfoque Bayesiano. Um estudo de simulação Monte Carlo foi conduzido e indicou um bom desempenho em termos de inferência, especialmente para o caso Bayesiano. Uma análise foi conduzida para um conjunto de dados reais envolvendo pacientes com melanoma, atendidos no Hospital das Clínicas/UFMG. Esse conjunto de dados é relativamente novo e apresenta simultaneamente o problema da VM e fração de indivíduos curados.https://orcid.org/0000-0002-8761-8705BrasilICX - DEPARTAMENTO DE ESTATÍSTICAPrograma de Pós-Graduação em EstatísticaUFMGORIGINALTese_Frederico_Machado.pdfapplication/pdf13283088https://repositorio.ufmg.br//bitstreams/2b7aa9d9-82e0-49ca-8832-4515a223dc2a/download178f7b99ad72875891f909409b082d00MD51trueAnonymousREADCC-LICENSElicense_rdfapplication/octet-stream805https://repositorio.ufmg.br//bitstreams/2bbe98e0-83ca-4b15-9b3b-d3e56f1cba85/download00e5e6a57d5512d202d12cb48704dfd6MD52falseAnonymousREADLICENSElicense.txttext/plain2118https://repositorio.ufmg.br//bitstreams/80391c92-3a81-460a-a753-604c156eb0f0/downloadcda590c95a0b51b4d15f60c9642ca272MD53falseAnonymousREAD1843/380202025-09-08 21:12:11.464http://creativecommons.org/licenses/by-nd/3.0/pt/Acesso Abertoopen.accessoai:repositorio.ufmg.br:1843/38020https://repositorio.ufmg.br/Repositório InstitucionalPUBhttps://repositorio.ufmg.br/oairepositorio@ufmg.bropendoar:2025-09-09T00:12:11Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)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
dc.title.none.fl_str_mv Solutions to the monotone likelihood in the standard mixture Cure fraction model
dc.title.alternative.none.fl_str_mv Soluções para o problema da verossimilhança monótona no modelo de fração de Cura
title Solutions to the monotone likelihood in the standard mixture Cure fraction model
spellingShingle Solutions to the monotone likelihood in the standard mixture Cure fraction model
Frederico Machado Almeida
Estatística – Teses
Verossimilhança (Estatistica) - Teses
Estatística matemática – Teses
Inferência (Estatística) – Teses
Melanona - Teses
Cure rate models
EM algorithm
Firth method
Bayesian inference
Logistic link function
Melanoma
title_short Solutions to the monotone likelihood in the standard mixture Cure fraction model
title_full Solutions to the monotone likelihood in the standard mixture Cure fraction model
title_fullStr Solutions to the monotone likelihood in the standard mixture Cure fraction model
title_full_unstemmed Solutions to the monotone likelihood in the standard mixture Cure fraction model
title_sort Solutions to the monotone likelihood in the standard mixture Cure fraction model
author Frederico Machado Almeida
author_facet Frederico Machado Almeida
author_role author
dc.contributor.author.fl_str_mv Frederico Machado Almeida
dc.subject.por.fl_str_mv Estatística – Teses
Verossimilhança (Estatistica) - Teses
Estatística matemática – Teses
Inferência (Estatística) – Teses
Melanona - Teses
topic Estatística – Teses
Verossimilhança (Estatistica) - Teses
Estatística matemática – Teses
Inferência (Estatística) – Teses
Melanona - Teses
Cure rate models
EM algorithm
Firth method
Bayesian inference
Logistic link function
Melanoma
dc.subject.other.none.fl_str_mv Cure rate models
EM algorithm
Firth method
Bayesian inference
Logistic link function
Melanoma
description Survival models for situations where some individuals are long-term survivors, immune or non-susceptible to the event of interest are extensively studied in biomedical research. Fitting a regression can be problematic in situations involving small sample sizes with many censored times, since the maximum likelihood estimates of some coefficients may be infinity. This phenomenon is commonly known as Monotone Likelihood (ML), occurring in the presence of many categorical and unbalanced covariates. A well-known solution is an adaptation of the Firth's method, originally created to reduce the maximum likelihood estimation bias. The method ensures finite estimates by penalizing the likelihood function, where the penalty term might be interpreted as the Jeffreys invariant prior, largely used in the Bayesian framework. The ML issue in the context involving mixture cure models is a topic rarely discussed in the literature, and it configures a central contribution of this work. In order to handle this point in such context, we propose to derive the adjusted score function based on the Firth method. The second major contribution is to investigate other flexible penalty functions (prior distributions), in which all inference procedures will be based on the posterior samples. An extensive Monte Carlo simulation study indicates good inference performance for the penalized estimates, especially in the Bayesian framework. The analysis is illustrated through a real application involving patients with melanoma assisted at the Hospital das Clínicas/UFMG. This is a relatively novel data set affected by the monotone likelihood issue and containing cured individuals.
publishDate 2021
dc.date.accessioned.fl_str_mv 2021-09-14T21:39:26Z
2025-09-09T00:12:11Z
dc.date.available.fl_str_mv 2021-09-14T21:39:26Z
dc.date.issued.fl_str_mv 2021-07-01
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://hdl.handle.net/1843/38020
url https://hdl.handle.net/1843/38020
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv http://creativecommons.org/licenses/by-nd/3.0/pt/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nd/3.0/pt/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Universidade Federal de Minas Gerais
publisher.none.fl_str_mv Universidade Federal de Minas Gerais
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFMG
instname:Universidade Federal de Minas Gerais (UFMG)
instacron:UFMG
instname_str Universidade Federal de Minas Gerais (UFMG)
instacron_str UFMG
institution UFMG
reponame_str Repositório Institucional da UFMG
collection Repositório Institucional da UFMG
bitstream.url.fl_str_mv https://repositorio.ufmg.br//bitstreams/2b7aa9d9-82e0-49ca-8832-4515a223dc2a/download
https://repositorio.ufmg.br//bitstreams/2bbe98e0-83ca-4b15-9b3b-d3e56f1cba85/download
https://repositorio.ufmg.br//bitstreams/80391c92-3a81-460a-a753-604c156eb0f0/download
bitstream.checksum.fl_str_mv 178f7b99ad72875891f909409b082d00
00e5e6a57d5512d202d12cb48704dfd6
cda590c95a0b51b4d15f60c9642ca272
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
repository.name.fl_str_mv Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)
repository.mail.fl_str_mv repositorio@ufmg.br
_version_ 1862105702678396928