Randomized Trials Versus Common Sense and Clinical Observation: JACC Review Topic of the Week

Abstract

Concerns about the external validity of traditional randomized clinical trials (RCTs), together with the widespread availability of real-world data and advanced data analytic tools, have led to claims that common sense and clinical observation, rather than RCTs, should be the preferred method to generate evidence to support clinical decision-making. However, over the past 4 decades, results from well-done RCTs have repeatedly contradicted practices supported by common sense and clinical observation. Common sense and clinical observation fail for several reasons: incomplete understanding of pathophysiology, biases and unmeasured confounding in observational research, and failure to understand risks and benefits of treatments within complex systems. Concerns about traditional RCT models are legitimate, but randomization remains a critical tool to understand the causal relationship between treatments and outcomes. Instead, development and promulgation of tools to apply randomization to real-world data are needed to build the best evidence base in cardiovascular medicine.

Keywords: observational studies; randomized controlled trials; real-world data; surrogate endpoints.

Graphical abstract

Central Illustration

Randomization Is Critical for Understanding Treatment Effect Common sense and clinical observation may fail to accurately describe the effect of a treatment on outcomes for multiple reasons. Randomization bypasses these failure mechanisms, creating a controlled experiment to understand the true effect of a treatment on outcomes. When common sense and clinical observation are the basis for treatment decisions, there is great uncertainty about benefit and risk, such that treatments may be ineffective and/or put the patient at risk. In contrast, treatment decisions based on high-quality randomized controlled trials have well-defined benefit and risk profiles allowing for effective decision-making.