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Modified Haybittle–Peto group sequential designs for testing superiority and non‐inferiority hypotheses in clinical trials
Author(s) -
Lai Tze Leung,
Shih MeiChiung,
Zhu Guangrui
Publication year - 2006
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.2357
Subject(s) - type i and type ii errors , interim , sample size determination , computer science , sequential analysis , treatment and control groups , interim analysis , margin (machine learning) , test (biology) , clinical trial , statistics , mathematics , medicine , machine learning , archaeology , pathology , history , paleontology , biology
In designing an active controlled clinical trial, one sometimes has to choose between a superiority objective (to demonstrate that a new treatment is more effective than an active control therapy) and a non‐inferiority objective (to demonstrate that it is no worse than the active control within some pre‐specified non‐inferiority margin). It is often difficult to decide which study objective should be undertaken at the planning stage when one does not have actual data on the comparative advantage of the new treatment. By making use of recent advances in the theory of efficient group sequential tests, we show how this difficulty can be resolved by a flexible group sequential design that can adaptively choose between the superiority and non‐inferiority objectives during interim analyses. While maintaining the type I error probability at a pre‐specified level, the proposed test is shown to have power advantage and/or sample size saving over fixed sample size tests for either only superiority or non‐inferiority, and over other group sequential designs in the literature. Copyright © 2005 John Wiley & Sons, Ltd.