Abstract
The randomised controlled trial (RCT) has been considered for a long time as the gold standard for evidence generation to support regulatory decision making for medicines. The randomisation procedure involves an ethical dilemma since it means leaving the treatment choice to chance. Although currently contested, the ethical justification for the RCT that has gained widespread acceptance is the notion of 'clinical equipoise'. This state exists when "there is no consensus within the expert clinical community about the comparative merits of the alternatives to be tested"; it is argued that this confers the ethical grounds for the conduct of an RCT. The prominent position of the RCT is being challenged by new therapeutic modalities for which this study design may be unsuitable. Moreover, alternative approaches to evidence generation represent another area where innovation may have implications for the relevance of the RCT. Against the backdrop of the debate around the equipoise principle and some recent therapeutic and data analytical innovations, the aim of this article is to explore the current standing of the RCT from a regulatory perspective.