Social and Scientific History of Randomized Controlled Trials

The practice and conceptual foundations of randomized controlled trials have been changed both by societal forces and by generations of investigators committed to applying rigorous research methods to therapeutic evaluation. This chapter briefly discusses the emergence of key trial elements such as control groups, alternate allocation, blinding, placebos, and finally randomization. We then explore how shifting intellectual, social, political, economic, regulatory, ethical, and technological forces have shaped the ways that RCTs have taken form, the types of therapies explored, the ethical standards that have been prioritized, and the populations included in studies. This history has not been a simple, linear march of progress. We also highlight key challenges in the historical use of RCTs and the more recent expansion of concerns regarding competing commercial interests that can influence trial design. As investigators continue to advance the rigor of controlled trials amid these challenges, exploring the influence of historical contexts on clinical trial development can help us to understand the forces that may impact trials today.