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Detection of interactions between treatment effects and patient descriptors in clinical trials is critical for optimizing the drug development process. The increasing volume of data accumulated in clinical trials provides a unique opportunity to discover new biomarkers and further the goal of personalized medicine, but it also requires innovative robust biomarker detection methods capable of detecting non-linear, and sometimes weak, signals. We propose a set of novel univariate statistical tests, based on the theory of random walks, which are able to capture non-linear and non-monotonic covariate-treatment interactions. We also propose a novel combined test, which leverages the power of all of our proposed univariate tests into a single general-case tool. We present results for both synthetic trials as well as real-world clinical trials, where we compare our method with state-of-the-art techniques and demonstrate the utility and robustness of our approach.
In randomized clinical trials, adjustments for baseline covariates at both design and analysis stages are highly encouraged by regulatory agencies. A recent trend is to use a model-assisted approach for covariate adjustment to gain credibility and ef
Concerns have been expressed over the validity of statistical inference under covariate-adaptive randomization despite the extensive use in clinical trials. In the literature, the inferential properties under covariate-adaptive randomization have bee
Functional Magnetic Resonance Imaging (fMRI) maps cerebral activation in response to stimuli but this activation is often difficult to detect, especially in low-signal contexts and single-subject studies. Accurate activation detection can be guided b
We propose a novel adaptive design for clinical trials with time-to-event outcomes and covariates (which may consist of or include biomarkers). Our method is based on the expected entropy of the posterior distribution of a proportional hazards model.
Covariate adjustment is an important tool in the analysis of randomized clinical trials and observational studies. It can be used to increase efficiency and thus power, and to reduce possible bias. While most statistical tests in randomized clinical