Seamless phase 2/3 oncology trial design with flexible sample size determination.
flexible design
go/no-go criteria
seamless phase 2/3 design
symmetric sample size determination rule
Journal
Statistics in medicine
ISSN: 1097-0258
Titre abrégé: Stat Med
Pays: England
ID NLM: 8215016
Informations de publication
Date de publication:
15 Aug 2020
15 Aug 2020
Historique:
received:
20
06
2019
revised:
19
02
2020
accepted:
13
03
2020
pubmed:
28
4
2020
medline:
22
6
2021
entrez:
28
4
2020
Statut:
ppublish
Résumé
Conventional seamless phase 2/3 design with fixed sample size determination (SSD) has gained its popularity in oncology drug development due to attractive features such as significantly shortening the development timeline, minimizing sample size, as well as early decision making. However, this design is not immune to inaccurate treatment effect assumption when only limited efficacy data are available at study design stage. We propose an innovative seamless phase 2/3 study design with flexible SSD for oncology trials, in which the trial is designed under a distribution of treatment effect instead of one single assumption due to huge uncertainty of treatment effect at design stage and the sample size for end of phase 3 analysis is not predetermined at design stage, but rather dynamically determined based on observed treatment effect at phase 2 portion. Some practical sample size determination rules for end of phase 3 analysis will be discussed. The proposed design can lead to reduced sample size or/and improved power compared with conventional seamless phase 2/3 design with fixed SSD. This innovative study design can be especially useful for programs with aggressive development strategy to expedite the process in delivering efficacious treatment to patients.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2373-2386Informations de copyright
© 2020 John Wiley & Sons, Ltd.
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