Testing strategy in phase 3 trials with multiple doses.
multiple testing
phase 3 clinical trials
type I error rate control
Journal
Biometrical journal. Biometrische Zeitschrift
ISSN: 1521-4036
Titre abrégé: Biom J
Pays: Germany
ID NLM: 7708048
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
14
12
2017
revised:
14
11
2018
accepted:
19
11
2018
pubmed:
15
12
2018
medline:
31
7
2019
entrez:
15
12
2018
Statut:
ppublish
Résumé
In this paper, we consider multiplicity testing approaches mainly for phase 3 trials with two doses. We review a few available approaches and propose some new ones. The doses selected for phase 3 usually have the same or a similar efficacy profile, so they have some degree of consistency in efficacy. We review the Hochberg procedure, the Bonferroni procedure, and a few consistency-adjusted procedures, and suggest new ones by applying the available procedures to the pooled dose and the high dose, the dose that is thought to be more efficacious between two doses. The reason behind the idea is that the pooled dose and the high dose are more consistent than the original two doses if the high dose is more efficacious than the low dose. We compare all approaches via simulations and recommend using a procedure combining 4A and the pooling approach. We also discuss briefly the testing strategy for trials with more than two doses.
Identifiants
pubmed: 30548293
doi: 10.1002/bimj.201700312
doi:
Types de publication
Journal Article
Langues
eng
Pagination
115-125Informations de copyright
© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.