Adjusting for treatment crossover in a trametinib metastatic melanoma RCT: Identifying the appropriate method
Treatment crossover refers to the situation in randomised controlled trials (RCTs) where patients randomised to the control group switch to the experimental treatment. This leads to biased estimates of treatment effects if crossover is not appropriately controlled for. Several crossover adjustment methods are available, but previous research has shown that the optimal adjustment method depends upon the characteristics of the trial .
This study applies crossover adjustment methods to an RCT comparing trametinib to chemotherapy in patients with BRAFV600E/K mutation-positive advanced or metastatic melanoma (NCT01245062), and investigates which adjustment method best fits this case study. Patients enrolled in the METRIC clinical trial were randomised 2:1 to receive trametinib 2 mg once daily or chemotherapy (DTIC or paclitaxel). There were 273 patients in the primary efficacy population (trametinib, n = 178, chemotherapy, n = 95) and 64 (67.4%) chemotherapy control group patients switched onto the experimental treatment.