Criteria for dose-finding in two-stage seamless adaptive design.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Zheng, J; Chow, S-C

Published Date

  • 2019

Published In

Volume / Issue

  • 29 / 5

Start / End Page

  • 908 - 919

PubMed ID

  • 31495271

Electronic International Standard Serial Number (EISSN)

  • 1520-5711

Digital Object Identifier (DOI)

  • 10.1080/10543406.2019.1657130


  • eng

Conference Location

  • England