Criteria for dose-finding in two-stage seamless adaptive design.
J Biopharm Stat
; 29(5): 908-919, 2019.
Article
em En
| MEDLINE
| ID: mdl-31495271
ABSTRACT
In pharmaceutical/clinical development, two-stage seamless adaptive designs are commonly considered. Such designs include a two-stage phase I/II or phase II/III adaptive trial that combines one phase IIb study for dose-finding or treatment selection and one phase III study for efficacy confirmation into a single study. At the end of stage 1, promising dose(s) will be selected based on pre-specified selection criteria. In practice, since there is little power with limited subjects available at interim, commonly considered selection criteria for critical decision-making include (i) conditional power, (ii) precision analysis, (iii) predictive probability of success, and (iv) probability of being the best dose or treatment. The selected promising dose(s) will then proceed to the next stage for efficacy confirmation. In this article, we introduce, compare, and evaluate these criteria. Simulation studies and a numeric example are given to illustrate those criteria. Besides, we attempt to address some concerns for the two-stage seamless adaptive clinical trial.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fármacos Cardiovasculares
/
Ensaios Clínicos Controlados Aleatórios como Assunto
/
Probabilidade
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Estudos Multicêntricos como Assunto
/
Determinação de Ponto Final
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article