Adaptive designs for selecting drug combinations based on efficacy–toxicity response

We propose a new adaptive procedure for dose-finding in clinical trials with combination of two drugs when both efficacy and toxicity responses are available. We model the distribution of this bivariate binary endpoint using the bivariate probit model. The analytic formulae for the Fisher informatio...

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Bibliographic Details
Published in:Journal of statistical planning and inference 2008-02, Vol.138 (2), p.352-373
Main Authors: Dragalin, Vladimir, Fedorov, Valerii, Wu, Yuehui
Format: Article
Language:English
Subjects:
Adaptive design
Bivariate probit model
Dose-finding
Dose–response
Drug combination
Early phase clinical trials
Information matrix
Optimal experimental design
Optimal safe dose
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Summary:We propose a new adaptive procedure for dose-finding in clinical trials with combination of two drugs when both efficacy and toxicity responses are available. We model the distribution of this bivariate binary endpoint using the bivariate probit model. The analytic formulae for the Fisher information matrix are obtained, that form the basis for derivation of the locally optimal, minimax, Bayesian, and adaptive designs in the framework of optimal design theory.
ISSN:0378-3758
1873-1171
DOI:10.1016/j.jspi.2007.06.017