Causality between tobacco use and cancer was established in the late 1960s through the application of Bradford Hill criteria, mechanistic research, and animal studies, not RCTs.

“once causality could be unambiguously established for tobacco use and cancer um which really occurred in the late 60s and by the way it was it didn't occur through rcts right it occurred through a very careful application of the Bradford Hill criteria um coupled with some mechanistic and and and animal research obviously no one could do the RC C to demonstrate the harm of tobacco and um with respect to to to cancer but nevertheless once causality was established the the the the die was cast for the monotonic decrease in tobacco consumption that has occurred over the last 50 years”