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Optimal biological dose selection in dose-finding trials with model-assisted designs based on efficacy and toxicity: a simulation study.
Yamaguchi, Yusuke; Takeda, Kentaro; Yoshida, Satoshi; Maruo, Kazushi.
Afiliação
  • Yamaguchi Y; Astellas Pharma Global Development, Inc, Northbrook, Illinois, USA.
  • Takeda K; Astellas Pharma Global Development, Inc, Northbrook, Illinois, USA.
  • Yoshida S; Data Science, Astellas Pharma Inc, Tokyo, Japan.
  • Maruo K; Department of Biostatistics, University of Tsukuba, Tsukuba, Japan.
J Biopharm Stat ; 34(3): 379-393, 2024 May.
Article em En | MEDLINE | ID: mdl-37114985
ABSTRACT
With the emergence of molecular targeted agents and immunotherapies in anti-cancer treatment, a concept of optimal biological dose (OBD), accounting for efficacy and toxicity in the framework of dose-finding, has been widely introduced into phase I oncology clinical trials. Various model-assisted designs with dose-escalation rules based jointly on toxicity and efficacy are now available to establish the OBD, where the OBD is generally selected at the end of the trial using all toxicity and efficacy data obtained from the entire cohort. Several measures to select the OBD and multiple methods to estimate the efficacy probability have been developed for the OBD selection, leading to many options in practice; however, their comparative performance is still uncertain, and practitioners need to take special care of which approaches would be the best for their applications. Therefore, we conducted a comprehensive simulation study to demonstrate the operating characteristics of the OBD selection approaches. The simulation study revealed key features of utility functions measuring the toxicity-efficacy trade-off and suggested that the measure used to select the OBD could vary depending on the choice of the dose-escalation procedure. Modelling the efficacy probability might lead to limited gains in OBD selection.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Projetos de Pesquisa / Neoplasias Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Projetos de Pesquisa / Neoplasias Idioma: En Ano de publicação: 2024 Tipo de documento: Article