Design and analysis of clinical trials in transplantation: principles and pitfalls

Abstract

The contributions of prospective randomized controlled trials (RCTs) to the advancement of solid organ transplantation are well appreciated. However, some misconception exists that results deriving from RCTs uniformly provide clinically relevant, definitive and generalized evidence. While there is little doubt that RCTs are the gold standard to test cause-and-effect relationships, the quality and subsequent utility of trials carried out in this field vary substantially. As with all other disciplines, our ability to interpret and implement the findings of RCTs into practice is strongly dependent on the study design and statistical rigor of the analysis. Failure to conduct trials with appropriate standards or interpret trials with the appropriate limitations may place patients at risk or waste valuable healthcare resources. The purpose of this review is to delineate important principles of study design and analysis of RCTs that are commonly overlooked. This review will discuss possible limitations of trials with specific applications in the field of transplantation. Progress in the field of transplantation is highly dependent on critical examination of existing clinical trials and vigilance regarding the optimal development of future trials.