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

TitleSeamless Phase IIa/IIb and enhanced dose-finding adaptive design.
Publication TypeJournal Article
Year of Publication2016
AuthorsYuan, Jiacheng, Herbert Pang, Tiejun Tong, Dong Xi, Wenzhao Guo, and Peter Mesenbrink
JournalJ Biopharm Stat
Date Published2016
KeywordsClinical Trials, Phase II as Topic, Dose-Response Relationship, Drug, Drug Design, Humans, Probability, Research Design, Sample Size

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.

Alternate JournalJ Biopharm Stat
Original PublicationSeamless phase IIa/IIb and enhanced dose-finding adaptive design.
PubMed ID26390951
PubMed Central IDPMC5025390
Grant ListP01 CA142538 / CA / NCI NIH HHS / United States