Extensions of the 2-in-1 adaptive design.
2-in-1 design
Intermediate endpoint
Seamless phase 2/3 design
Slepian's lemma
Journal
Contemporary clinical trials
ISSN: 1559-2030
Titre abrégé: Contemp Clin Trials
Pays: United States
ID NLM: 101242342
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
19
12
2019
revised:
30
03
2020
accepted:
31
05
2020
pubmed:
7
6
2020
medline:
25
9
2021
entrez:
7
6
2020
Statut:
ppublish
Résumé
The 2-in-1 adaptive design [Chen et al. 2018] allows seamless expansion of an ongoing Phase 2 trial into a Phase 3 trial to expedite a drug development program. An intermediate endpoint can be used for the adaptive decision. Under a mild assumption that is expected to generally hold in practice, both the Phase 2 trial (in case of no expansion) and the Phase 3 trial (in case of expansion) can be tested at the full alpha level without inflating the overall Type I error of the study. Due to its flexibility and robustness, the design has quickly generated a lot of interest since its recent publication. We make three major extensions to the 2-in-1 design in this paper: 1) an increase of adaptive decisions from two to any number; 2) incorporation of the group sequential method for data monitoring; 3) expansion of the univariate design to multivariate. These extensions not only facilitate the application of 2-in-1 design in practice but also stimulate research interest in related statistical issues. Although we mainly use hypothetical trials in oncology and neuroscience for illustration, the application of the 2-in-1 design and its extensions is not limited to the two therapeutic areas.
Identifiants
pubmed: 32504820
pii: S1551-7144(20)30131-2
doi: 10.1016/j.cct.2020.106053
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
106053Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.