Randomised clinical trials (RCTs) remain the gold standard of evidence for the benefit of new therapeutics but standard designs fit awkwardly with key developments in biomarker-stratified drug development. Firstly, the unprecedented number of new agents being developed in oncology (usually with specific targets for which there may be predictive biomarkers) mandates a need for new trial designs that are more efficient in screening out new agents with modest likelihood of benefit, concentrating resources on the most promising ones. The multi-arm multi-stage (MAMS) design developed some years ago addresses this need. Secondly, biomarker-stratified trials, when tackled one biomarker/drug pairing at a time, are inherently highly inefficient. The FOCUS4 trial design was developed to overcome this problem, using a platform that incorporates multiple parallel biomarker-stratified RCTs in individual cohorts, and capable of adapting its design in response to developing evidence.
Keywords: Stratified medicine; biomarkers; colorectal cancer; trials design.