Improving combination drug trials using ‘definitive screening designs’

As developers of high-complexity biologic cocktails, we read with interest the Feature by Strohbehn et al.1 in the December 2021 issue of Nature Biotechnology voicing concerns about the risk of unjustified patents for arguably obvious drug combinations. The current approach to clinical trial design is built for the development of single-agent therapies; it lacks the scalability needed to systemati-cally explore the entire design space of com-bination therapies. Full factorial trial designs exploring all possible combinations and dosage levels would be infeasible even for the largest biopharmaceutical companies. Against this backdrop, it is not surprising that drug developers focus their efforts on the much smaller set of obvious combinations.