Seamless Phase IIa/IIb and enhanced dose-finding adaptive design.

Journal Article (Journal Article)

In drug development, when the drug class has a relatively well-defined path to regulatory approval and the enrollment is slow with certain patient populations, one may want to consider combining studies of different phases. This article considers combining a proof of concept (POC) study and a dose-finding (DF) study with a control treatment. Conventional DF study designs sometimes are not efficient, or do not have a high probability to find the optimal dose(s) for Phase III trials. This article seeks more efficient DF strategies that allow the economical testing of more doses. Hypothetical examples are simulated to compare the proposed adaptive design vs. the conventional design based on different models of the overall quantitative representation of efficacy, safety, and tolerability. The results show that the proposed adaptive design tests more active doses with higher power and comparable or smaller sample size in a shorter overall study duration for POC and DF, compared with a conventional design.

Full Text

Duke Authors

Cited Authors

  • Yuan, J; Pang, H; Tong, T; Xi, D; Guo, W; Mesenbrink, P

Published Date

  • 2016

Published In

Volume / Issue

  • 26 / 5

Start / End Page

  • 912 - 923

PubMed ID

  • 26390951

Pubmed Central ID

  • PMC5025390

Electronic International Standard Serial Number (EISSN)

  • 1520-5711

Digital Object Identifier (DOI)

  • 10.1080/10543406.2015.1094807


  • eng

Conference Location

  • England