When biological complexity demands more than better trial designs

The increasing complexity of precision medicine has highlighted the limitations of traditional randomized clinical trials (RCTs) when applied to highly stratified populations and biologically heterogeneous diseases. In this context, master protocols represent an evolution towards integrated experimental infrastructures, capable of simultaneously evaluating multiple interventions or molecular subgroups within a single methodological framework. These designs redefine the role of randomization in complex settings. Conventional RCTs remain indispensable as confirmatory studies, thanks to their methodological rigor and the robustness of the evidence they generate. Future developments will depend on the capacity to ensure statistical rigor, transparent governance, data protection and equitable access to experimental infrastructures and advanced molecular screening. In this evolving landscape, master protocols emerge not as a methodological trend, but as one of the most convincing tools for making evidence generation faster, more flexible, and more sustainable without giving up the scientific standards required by contemporary clinical research.