Are randomized controlled trials as gold standard for high level evidence a pragmatic approach in the era of precision medicine and real-world evidence

Abstract

Randomized controlled trials (RCTs) have been considered as the gold standard for evaluating medical interventions due to their robust methodology, limited introduction of bias, and strength in establishing strong evidence to show better effect of a treatment option. However, the evolving landscape of healthcare—marked by precision medicine, digital health technologies, and expanding access to real-world data—has exposed important limitations in the traditional dominance of RCTs. These include issues of generalizability, cost, ethical constraints, and limited applicability in heterogeneous patient populations, particularly in low- and middle-income countries. Concurrently, the emergence of real-world evidence, pragmatic trials, and adaptive designs has introduced complementary paradigms that challenge the exclusivity of RCTs in evidence hierarchies. This editorial provides a critical and expanded appraisal of the role of RCTs in contemporary medicine, examining their enduring strengths alongside their limitations, and highlighting the need for an integrated, context-sensitive approach to evidence generation.