Poorly Recognized and Uncommonly Acknowledged Limitations of Randomized Controlled Trials

Abstract

Randomized controlled trials (RCTs) are a gold standard in evidence-based research. However, RCTs have limitations, among which the most commonly acknowledged is that narrow study selection criteria compromise the external validity of the findings. This article briefly touches upon this and other well-recognized limitations and presents, in greater detail, less commonly acknowledged limitations with examples from contemporary literature. Important among the less commonly acknowledged limitations are biases in RCTs of interventions to which patients cannot be blinded, weaknesses in the design of maintenance therapy RCTs, and, ubiquitously, post-randomization biases. The listed limitations notwithstanding, RCTs are still the best among research designs. What is important is to recognize the imperfections in each RCT so that the findings of the RCT can be better judged.

Keywords: Randomized controlled trials; blinding; external validity post-randomization bias; internal validity; limitations.