Randomized controlled trials (RCTs) have become the gold standard of clinical evidence and the staple of guided clinical practice. RCTs are based on a complex set of principles and procedures heavily strung by statistical analysis, primarily designed to answer a specific question in a clinical experiment. Readers of clinical trials need to apply critical appraisal skills before blindly accepting the results and conclusions of trials, lest they misinterpret and misapply the findings. We introduce the fundamentals of an RCT and discuss the relationship between relative risk (RR) and absolute risk (AR) in terms of the different information each conveys. The top results of some recent cardiovascular outcome trials using sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in patients with type 2 diabetes are used to exemplify the merit of assessing both RR and AR changes for a balanced translation of findings into shrewd clinical judgment. We also suggest practical points to assist with a clinically useful interpretation of both within-trial and across-trial reports. Finally, we mention an alternative approach, namely, the restricted mean survival time, to obtaining unbiased estimates of the mean time of missed events in the treatment versus placebo arm for the duration of the trial.
Ele Ferrannini, Julio Rosenstock