There is an article in Medscape titled "Antidepressant-Induced Suicidality: How Translational Epidemiology Incorporating Pharmacogenetics Into Controlled Trials Can Improve Clinical Care" which is a mouth full but contains some interesting information about how RCTs came about. PR
medscape.com/viewarticle/82...
"Randomized controlled trials (RCTs) have been a staple of the drug development process for several decades. Here, we review the origins of RCTs and their adoption within drug development, highlighting shortcomings that tend to be ignored and possible solutions offered from personalized medicine. While RCTs play an important role in development of therapeutics, we underscore how if used indiscriminately, their adverse effects may outweigh the benefits. As an example, we focus on the development of antidepressants and how a severe adverse drug response – suicidal ideation – can be overlooked."