Robust Detection of Covariate-Treatment Interactions in Clinical Trials

Designing new and efficient therapies is a long and ever more costly process, with less than ten percent of new treatments entering Phase I finally being approved by the FDA and commercialized [1, 2]. One of the major challenges for the improvement of drug development is to better understand how drugs interact with patients, particularly for treatments displaying heterogeneous responses. Therefore, conducting a detailed analysis of clinical trial data is critical to find subgroups of patients with higher benefit-risk ratio or to understand why a drug does not work on some subpopulation to improve existing therapeutic strategies. Moreover, understanding the relationships of patient descriptors which compose the most responsive cross-section of the population is of great importance when planning a Phase III trial, for salvaging failed trials, or accelerating advances in personalized medicine. This process of biomarker identification is critical to detect subgroups within a given indication, but, as shown recently for immunotherapies, can also provide the basis for pan-indication drug approval [3].