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Master's Dissertation
DOI
https://doi.org/10.11606/D.104.2019.tde-03012019-102102
Document
Author
Full name
Bruna Aparecida Barbosa Marins
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Carlos, 2018
Supervisor
Committee
Cobre, Juliana (President)
Dias, Teresa Cristina Martins
Silva, Gisela Tunes da
Title in Portuguese
Estudo do impacto da escolha do modelo para o controle de overdose na fase I dos ensaios clínicos
Keywords in Portuguese
Chances de sobrevivências proporcionais
Controle de overdose
Dose máxima tolerada
Riscos proporcionais
Abstract in Portuguese
Escalonamento com controle de overdose (EWOC-PH, escalation with overdose control proporcional hazards) é um método bayesiano com controle de overdose que estima a dose máxima tolerada (MTD, maximum tolerated dose) assumindo que o tempo que um paciente leva para apresentar toxicidade segue o modelo de riscos proporcionais. Neste trabalho analisamos quais são as consequências em adotarmos um método que se baseia no modelo de riscos proporcionais quando o tempo até toxicidade segue o modelo de chances de sobrevivência proporcionais. A fim de buscar responder se teríamos uma superestimativa ou uma subestimativa da MTD foram feitas simulações em que consideramos dados de chances de sobrevivência proporcionais e aplicação do método EWOC-PH para analisarmos a MTD. Como uma extensão do método EWOC-PH, propomos o método EWOC-POS que assume que os tempos seguem o modelo de chances de sobrevivência proporcionais.
Title in English
Study of the impact of model choice for overdose control in phase I of clinical trials
Keywords in English
Maximum tolerated dose
Overdose control
Proportional hazards
Proportional odds survival
Abstract in English
Escalation with overdose control proportional hazards is a Bayesian method with overdose control that estimates the maximum tolerated dose (MTD) assuming that the time a patient takes to show toxicity follows the proportional hazards model. In this work, we analyse the consequences of adopting a method based on the proportional hazard model when the time until toxicity follows the proportional survival model. In order to seek to answer if we would have an overestimate or an underestimate of MTD, simulations were performed in which we considered proportional odds survival data and application of the EWOC-PH method. As an extension of the EWOC-PH method, we propose the EWOC-POS method which assumes that time until toxicity follows the proportional odds survival model.
 
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Publishing Date
2019-01-03
 
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