Response adaptive designs for Phase II trials with binary endpoint based on context-dependent information measures.
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Publication Date
2021-06Journal Title
Computational Statistics and Data Analysis
ISSN
0167-9473
Publisher
Elsevier
Volume
158
Number
107187
Pages
107187-107187
Type
Article
This Version
VoR
Metadata
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Kasianova, K., Kelbert, M., & Mozgunov, P. (2021). Response adaptive designs for Phase II trials with binary endpoint based on context-dependent information measures.. Computational Statistics and Data Analysis, 158 (107187), 107187-107187. https://doi.org/10.1016/j.csda.2021.107187
Abstract
In many rare disease Phase II clinical trials, two objectives are of interest to an investigator: maximising the statistical power and maximising the number of patients responding to the treatment. These two objectives are competing, therefore, clinical trial designs offering a balance between them are needed. Recently, it was argued that response-adaptive designs such as families of multi-arm bandit (MAB) methods could provide the means for achieving this balance. Furthermore, response-adaptive designs based on a concept of context-dependent (weighted) information criteria were recently proposed with a focus on Shannon's differential entropy. The information-theoretic designs based on the weighted Renyi, Tsallis and Fisher informations are also proposed. Due to built-in parameters of these novel designs, the balance between the statistical power and the number of patients that respond to the treatment can be tuned explicitly. The asymptotic properties of these measures are studied in order to construct intuitive criteria for arm selection. A comprehensive simulation study shows that using the exact criteria over asymptotic ones or using information measures with more parameters, namely Renyi and Tsallis entropies, brings no sufficient gain in terms of the power or proportion of patients allocated to superior treatments. The proposed designs based on information-theoretical criteria are compared to several alternative approaches. For example, via tuning of the built-in parameter, one can find designs with power comparable to the fixed equal randomisation's but a greater number of patients responded in the trials.
Sponsorship
Department of Health (via National Institute for Health Research (NIHR)) (NIHR300576)
Identifiers
External DOI: https://doi.org/10.1016/j.csda.2021.107187
This record's URL: https://www.repository.cam.ac.uk/handle/1810/335810
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