Biomarker-adaptive clinical trial designs

Advancements made in molecularly targeted therapeutics have focused increasing attention on biomarker-adaptive clinical trial designs as a means of improving the efficiency of drug development and advancing medical care. Here, we focus on randomized clinical trial (RCT) designs aimed at developing/validating clinically relevant biomarkers capable of identifying patients sensitive to a given therapy(s), and thereby, selecting the best therapy for a given patient. The term ‘biomarker-adaptive’ refers to biomarker trials that incorporate adaptive clinical trial methodology to modify the trial according to the accumulating outcome data. While some adaptive methods (e.g., interim monitoring) have been an integral part of traditional clinical trial design for decades, these methods can be particularly advantageous in biomarker studies that evaluate molecularly targeted therapies. Here, we briefly review the main clinical trial methods that are used in designing adaptive trials. We then discuss how these methods can be used to improve the efficiency of biomarker RCT designs