An example of the marker-by-treatment-interaction design is the phase III biomarker validation study, known as MARVEL (Marker Validation of Erlotinib in Lung Cancer), of second-line therapy in patients with advanced NSCLC randomly assigned to pemetrexed or erlotinib based on epidermal growth factor receptor (EGFR) status as measured by fluorescence in situ hybridization (FISH) [19]. This evidence concerns the gene EGFR and lung carcinoma.