The cornerstones of randomized clinical trials

Abstract

Randomized clinical trials (RCTs) are pivotal in medical research, offering critical evidence on the efficacy and safety of treatments. This paper explores the distinct purposes and designs of superiority, non-inferiority, equivalence, and pragmatic trials, each addressing unique research questions. Superiority trials aim to demonstrate a new treatment's effectiveness over existing standards, while non-inferiority and equivalence trials focus on ensuring new treatments are not significantly worse or are similar to existing ones, respectively. Pragmatic trials assess interventions in real-world settings. A fundamental ethical principle in RCTs is clinical equipoise, ensuring unbiased treatment allocation. The CONSORT statement provides guidelines for transparent reporting of RCTs, enhancing the reliability of findings. Key methodological considerations include sample size calculation, randomization, blinding, and the choice between intention-to-treat and per-protocol analyses. Stratified analysis and forest plots further aid in understanding treatment effects across diverse populations. By adhering to these principles, RCTs remain a cornerstone of evidence-based medical practice, advancing patient care and outcomes.

Keywords: CONSORT; Equipoise; Equivalence trial; Intention to treat analysis; Non-inferiority trials; Per protocol analysis; Pragmatic trials; Randomization; Randomized clinical trials; Superiority trials.