Kimani, Peter K., Todd, Susan and Stallard, Nigel (2015) Estimation after subpopulation selection in adaptive seamless trials. Statistics in Medicine, 34 (18). pp. 2581-2601. doi:10.1002/sim.6506 ISSN 0277-6715.

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Abstract

During the development of new therapies, it is not uncommon to test whether a new treatment works better than the existing treatment for all patients who suffer from a condition (full population) or for a subset of the full population (subpopulation). One approach that may be used for this objective is to have two separate trials, where in the first trial, data are collected to determine if the new treatment benefits the full population or the subpopulation. The second trial is a confirmatory trial to test the new treatment in the population selected in the first trial. In this paper, we consider the more efficient two-stage adaptive seamless designs (ASDs), where in stage 1, data are collected to select the population to test in stage 2. In stage 2, additional data are collected to perform confirmatory analysis for the selected population. Unlike the approach that uses two separate trials, for ASDs, stage 1 data are also used in the confirmatory analysis. Although ASDs are efficient, using stage 1 data both for selection and confirmatory analysis introduces selection bias and consequently statistical challenges in making inference. We will focus on point estimation for such trials. In this paper, we describe the extent of bias for estimators that ignore multiple hypotheses and selecting the population that is most likely to give positive trial results based on observed stage 1 data. We then derive conditionally unbiased estimators and examine their mean squared errors for different scenarios. Copyright © 2015 John Wiley & Sons, Ltd.

Item Type:	Journal Article
Subjects:	R Medicine > RA Public aspects of medicine
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences > Statistics and Epidemiology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Clinical trials -- Methodology, Drugs -- Effectiveness
Journal or Publication Title:	Statistics in Medicine
Publisher:	John Wiley & Sons Ltd.
ISSN:	0277-6715
Official Date:	15 August 2015
Dates:	Date Event 15 August 2015 Published 22 April 2015 Available 22 March 2015 Accepted 24 December 2014 Modified 23 December 2013 Submitted
Volume:	34
Number:	18
Page Range:	pp. 2581-2601
DOI:	10.1002/sim.6506
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	29 December 2015
Date of first compliant Open Access:	29 December 2015
Adapted As:

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