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Advances in high-throughput biological technologies have led to large numbers of potentially predictive biomarkers becoming routinely measured in modern clinical trials. Biomarkers which influence treatment efficacy may be used to find subgroups of patients who are most likely to benefit from a new treatment. Consequently, there is a growing interest in better approaches to identify biomarker signatures and utilize the biomarker information in clinical trials. The first focus of this thesis is on developing methods for detecting biomarker-treatment interactions in large-scale trials. Traditional interaction analysis, using regression models to test biomarker-treatment interactions one biomarker at a time, may suffer from poor power when there is a large multiple testing burden. I adapt recently proposed two-stage interaction detecting procedures for application in randomized clinical trials. I propose two new stage 1 multivariate screening strategies using lasso and ridge regressions to account for correlations among biomarkers. For these new multivariate screening strategies, I prove the asymptotic between-stage independence, required for family-wise error rate control. Simulation and real data application results are presented which demonstrate greater power of the new strategies compared with previously existing approaches. The second focus of this thesis is on developing methods for utilizing biomarker information during the course of a randomized clinical trial to improve the informativeness of results. Under the adaptive signature design (ASD) framework, I propose two new classifiers that more efficiently leverage biomarker signatures to select a subgroup of patients who are most likely to benefit from the new treatment. I provide analytical arguments and demonstrate through simulations that these two proposed classification criteria can provide at least as good, and sometimes significantly greater power than the originally proposed ASD classifier. Third, I focus on an important issue in the statistical analysis of interactions for binary outcomes, which is pertinent to both topics above. Testing for biomarker-treatment interactions with logistic regression can suffer from an elevated number of type I errors due to the asymptotic bias of the interaction regression coefficient under model misspecification. I analyze this problem in the randomized clinical trial setting and propose two new de-biasing procedures, which can offer improved family-wise error rate control in various simulated scenarios. Finally, I summarize the main contributions from the work above, discuss some practical limitations as well as their real world value, and prioritize future directions of research building upon the work in this thesis., Medical Research Council, grant ID: MR/R502303/1