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Adaptive enrichment designs with a continuous biomarker
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Stallard, Nigel (2023) Adaptive enrichment designs with a continuous biomarker. Biometrics, 79 (1). pp. 9-19. doi:10.1111/biom.13644 ISSN 0006-341X.
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Official URL: https://doi.org/10.1111/biom.13644
Abstract
A popular design for clinical trials assessing targeted therapies is the two-stage adaptive enrichment design with recruitment in stage two limited to a biomarker-defined subgroup chosen based on data from stage one. The data-dependent selection leads to statistical challenges if data from both stages are used to draw inference on treatment effects in the selected subgroup.
If subgroups considered are nested, as when defined by a continuous biomarker, treatment effect estimates in different subgroups follow the same distribution as estimates in a group-sequential trial. This result is used to obtain tests controlling the familywise type I error rate (FWER) for six simple subgroup selection rules, one of which also controls the FWER for any selection rule. Two approaches are proposed; one based on multivariate normal distributions suitable if the number of possible subgroups, k, is small, and one based on Brownian motion approximations suitable for large k. The methods, applicable in the wide range of settings with asymptotically normal test statistics, are illustrated using survival data from a breast cancer trial.
Item Type: | Journal Article | ||||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Journal or Publication Title: | Biometrics | ||||||||
Publisher: | John Wiley & Sons Ltd. | ||||||||
ISSN: | 0006-341X | ||||||||
Official Date: | March 2023 | ||||||||
Dates: |
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Volume: | 79 | ||||||||
Number: | 1 | ||||||||
Page Range: | pp. 9-19 | ||||||||
DOI: | 10.1111/biom.13644 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Reuse Statement (publisher, data, author rights): | This is the peer reviewed version of the following article: Stallard, N. (2022), Adaptive enrichment designs with a continuous biomarker. Biometrics., which has been published in final form at https://doi.org/10.1111/biom.13644. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. | ||||||||
Access rights to Published version: | Restricted or Subscription Access | ||||||||
Date of first compliant deposit: | 27 September 2021 | ||||||||
Date of first compliant Open Access: | 17 February 2023 | ||||||||
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