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Estimation after subpopulation selection in adaptive seamless trials
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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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Official URL: http://dx.doi.org/10.1002/sim.6506
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 | ||||||||||||
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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 |
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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: |
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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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