Kimani, Peter K., Todd, Susan C. and Stallard, Nigel (2013) Conditionally unbiased estimation in phase II/III clinical trials with early stopping for futility. Statistics in Medicine, Volume 32 (Number 17). pp. 2893-2901. doi:10.1002/sim.5757 ISSN 0277-6715.

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Abstract

Seamless phase II/III clinical trials combine traditional phases II and III into a single trial that is conducted in two stages, with stage 1 used to answer phase II objectives such as treatment selection and stage 2 used for the confirmatory analysis, which is a phase III objective. Although seamless phase II/III clinical trials are efficient because the confirmatory analysis includes phase II data from stage 1, inference can pose statistical challenges. In this paper, we consider point estimation following seamless phase II/III clinical trials in which stage 1 is used to select the most effective experimental treatment and to decide if, compared with a control, the trial should stop at stage 1 for futility. If the trial is not stopped, then the phase III confirmatory part of the trial involves evaluation of the selected most effective experimental treatment and the control. We have developed two new estimators for the treatment difference between these two treatments with the aim of reducing bias conditional on the treatment selection made and on the fact that the trial continues to stage 2. We have demonstrated the properties of these estimators using simulations. Copyright © 2013 John Wiley & Sons, Ltd.

Item Type:	Journal Article
Subjects:	Q Science > QA Mathematics R Medicine > RS Pharmacy and materia medica
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Drugs -- Testing , Clinical trials, Clinical pharmacology, Medical statistics, Medicine -- Mathematics
Journal or Publication Title:	Statistics in Medicine
Publisher:	John Wiley & Sons Ltd.
ISSN:	0277-6715
Official Date:	30 July 2013
Dates:	Date Event 30 July 2013 Published
Volume:	Volume 32
Number:	Number 17
Page Range:	pp. 2893-2901
DOI:	10.1002/sim.5757
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	24 December 2015
Date of first compliant Open Access:	24 December 2015

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