Despite concerns that traditional randomized clinical trials (RCTs) have "become too complex and selective," they remain the "best current method to understand the causal relationship between an intervention and subsequent population-level outcomes for most common chronic illnesses," according to a review paper published July 27 in the Journal of the American College of Cardiology.

Alexander C. Fanaroff, MD, MHS, et al., compare use of RCTs vs. common sense and clinical observation to support clinical decision-making. The review is relevant in the COVID-19 era when the need for effective treatment has led to proposed "common sense" proposed treatments, with some arguments that RCTs will delay treatment. The authors note that the review "underscores the flaws in such reasoning and highlights the limitations of nonrandomized" trials.

According to the authors, common sense and clinical observation may fail because of incomplete understanding of pathophysiology, biases and unmeasured confounding in observational research, and failure to understand risks and benefits of treatments within complex systems, the paper notes.

Real-world data sources have helped identify rare adverse events but have also been limited in understanding the effects of treatments, the authors note. Moving forward, randomization should be applied broadly to real-world data to understand treatment effects and produce large, representation study populations, they write, adding that this will require investment in electronic health records and interoperability, as well as the ability to enroll patients in RCTs and gather research data. In addition, these efforts will require collaboration among health systems, regulatory authorities, researchers, and pharmaceutical and device industries.

Adapting traditional RCTs "within the real world will require a reimagining of the clinical research enterprise, but the alternative is capitulating and basing treatment decisions on common sense and clinical observation," the authors write. "As the experience of the past 40 years shows, there is no substitution for randomization," they conclude.

Clinical Topics: COVID-19 Hub

Keywords: Electronic Health Records, Decision Making, COVID-19, Random Allocation, severe acute respiratory syndrome coronavirus 2, Information Storage and Retrieval, Treatment Outcome, Chronic Disease, Risk Assessment, Pharmaceutical Preparations, Randomized Controlled Trial

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