The Range and Scientific Value of Randomized Trials

Abstract

Background: The randomized, controlled trial (RCT) is the gold standard of scientific evidence for the attribution of clinical effects (benefits and harms) to medical interventions. Many different designs for RCTs have been developed in order to counter legitimate critical objections and to better adapt the trials to the continually changing challenges that face clinical research.

Methods: The diversity and adaptability of randomized trial designs are presented and discussed on the basis of a selective literature review and specific illustrative examples.

Results: A wide range of RCT designs enables adaptation to special research tasks and clinical framework conditions. These include (among others) crossover trials, n=1 trials, factorial RCT designs, and cluster-randomized trials. In addition, adaptive designs such as modern platform trials and pragmatic RCTs with simplified clinical questions and less severely restricted patient groups make broad recruitment of patients possible even in routine clinical practice.

Conclusion: Only the randomized allocation of subjects to the treatment and control groups, which is the defining property of RCTs, can adequately ensure that traits of the subjects which might disturb or bias a comparison of two or more medical interventions, will be evenly distributed across groups, regardless of whether these traits are known or unknown. The methodological variants and further elaborations of the RCT that are discussed here will help protect patients by enabling the assessment of the benefits and harms of medical methods and products on the basis of robust evidence even in the present era of rapid innovation.