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Estimation of treatment effect in 2‐in‐1 adaptive design and some of its extensions
Author(s) -
Li Wen,
Bai Xiaofei,
Deng Qiqi,
Liu Fang,
Chen Cong
Publication year - 2021
Publication title -
statistics in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.996
H-Index - 183
eISSN - 1097-0258
pISSN - 0277-6715
DOI - 10.1002/sim.8917
Subject(s) - estimator , adaptive design , interim , computer science , estimation , interim analysis , field (mathematics) , phase (matter) , mathematical optimization , statistics , mathematics , clinical trial , medicine , archaeology , pathology , pure mathematics , economics , history , chemistry , organic chemistry , management
The 2‐in‐1 adaptive design allows seamless expansion of an ongoing Phase II trial into a Phase III trial to expedite a drug development program. Since its publication, it has generated a lot of interest. So far, most of the related research focused on type I error control. Similar to most adaptive designs, 2‐in‐1 design could also pose a great challenge on estimation of treatment effect due to the data‐driven adaptation. In addition, the use of intermediate endpoint for interim adaptive decision‐making is a less well‐studied field. In this paper, we investigate the bias and variances in estimation for 2‐in‐1 design and some of its extensions, and propose some bias‐adjusted estimators for 2‐in‐1 design. The properties of the proposed estimators are further studied theoretically and/or numerically, so as to provide guidance on how to interpret the estimated treatment effect of 2‐in‐1 design.