Unbiased estimation in seamless phase II/III trials with unequal treatment effect variances and hypothesis-driven selection rules
File(s)Robertson_et_al-2016-Statistics_in_Medicine.pdf (487.42 KB)
Published version
Author(s)
Robertson, DS
Prevost, AT
Bowden, J
Type
Journal Article
Abstract
Seamless phase II/III clinical trials offer an efficient way to select an experimental treatment and perform confirmatory analysis within a single trial. However, combining the data from both stages in the final analysis can induce bias into the estimates of treatment effects. Methods for bias adjustment developed thus far have made restrictive assumptions about the design and selection rules followed. In order to address these shortcomings, we apply recent methodological advances to derive the uniformly minimum variance conditionally unbiased estimator for two-stage seamless phase II/III trials. Our framework allows for the precision of the treatment arm estimates to take arbitrary values, can be utilised for all treatments that are taken forward to phase III and is applicable when the decision to select or drop treatment arms is driven by a multiplicity-adjusted hypothesis testing procedure. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.
Date Issued
2016-04-21
Date Acceptance
2016-04-01
Citation
Statistics in Medicine, 2016, 35 (22), pp.3907-3922
ISSN
1097-0258
Publisher
Wiley
Start Page
3907
End Page
3922
Journal / Book Title
Statistics in Medicine
Volume
35
Issue
22
Copyright Statement
© 2016 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Subjects
adaptive seamless designs
phase II/III clinical trials
treatment selection
uniformly minimum variance unbiased estimator
Publication Status
Published