Confidence regions for treatment effects in subgroups in biomarker stratified designs

Wan, Fang and Kunz, Cornelia Ursula and Jaki, Thomas Friedrich (2019) Confidence regions for treatment effects in subgroups in biomarker stratified designs. Biometrical Journal, 61 (1). pp. 27-39. ISSN 0323-3847

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Abstract

Subgroup analysis has important applications in the analysis of controlled clinical trials. Sometimes the result of the overall group fails to demonstrate that the new treatment is better than the control therapy, but for a subgroup of patients, the treatment benefit may exist; or sometimes, the new treatment is better for the overall group but not for a subgroup. Hence we are interested in constructing a simultaneous confidence interval for the difference of the treatment effects in a subgroup and the overall group. Subgroups are usually formed on the basis of a predictive biomarker such as age, sex, or some genetic marker. While, for example, age can be detected precisely, it is often only possible to detect the biomarker status with a certain probability. Because patients detected with a positive or negative biomarker may not be truly biomarker positive or negative, responses in the subgroups depend on the treatment therapy as well as on the sensitivity and specificity of the assay used in detecting the biomarkers. In this work, we show how (approximate) simultaneous confidence intervals and confidence ellipsoid for the treatment effects in subgroups can be found for biomarker stratified clinical trials using a normal framework with normally distributed or binary data. We show that these intervals maintain the nominal confidence level via simulations.

Item Type:
Journal Article
Journal or Publication Title:
Biometrical Journal
Additional Information:
This is the peer reviewed version of the following article: Wan F, Kunz CU, Jaki TF. Confidence regions for treatment effects in subgroups in biomarker stratified designs. Biometrical Journal. 2019; 61:27–39. https://doi.org/10.1002/bimj.201700303 which has been published in final form at https://onlinelibrary.wiley.com/doi/full/10.1002/bimj.201700303 This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2700
Subjects:
ID Code:
128061
Deposited By:
Deposited On:
12 Oct 2018 08:52
Refereed?:
Yes
Published?:
Published
Last Modified:
25 Oct 2020 05:53