Clinical trials also allow controlled comparisons for G×E interactions and more powerful designs using two-phase sampling on various combinations of genotype, treatment, outcomes, and possibly other factors93,125. For example, Israel et al.126 performed a clinical trial of albuteral in asthmatics, matching pairs on forced expiratory volume and β2AR genotypes, and found a highly significant gene × treatment interaction. A case-only design nested within a clinical trial is particularly appealing for evaluating gene-treatment interactions on survival or other treatment responses, as treatment assignment is independent of genotype by virtue of randomization127,128.
