Randomized, controlled, and real

Ali Al‐kassab‐Córdova

doi:10.1016/j.jclinepi.2026.112414

Randomized, controlled, and real

2026-07-01

1

PRE

AI

A

Ali Al‐kassab‐Córdova

S

Stephen Burgess

N

Nasir Zeeshan Bashir *

DOI：10.1016/j.jclinepi.2026.112414

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Objectives: The growing use of the term real-world evidence (RWE) has introduced a classification of clinical research based on its perceived proximity to routine practice rather than its methodological characteristics. Although the term is often used operationally to refer to evidence derived from routinely collected clinical data or routine care settings, it has also been criticized for implying that such studies are inherently closer to real life than traditional randomized controlled trials (RCTs). In this Commentary, we argue that such a distinction is conceptually misleading. Methods: A critical analysis of RWE terminology and its implications. Results: Both randomized and observational studies are conducted within the same empirical reality; what differentiates them is not their realness, but the methodological structures used to observe and analyze that reality. Randomization and other forms of experimental control do not detach research from real-world contexts but, rather, reduce systematic error and uncertainty to better isolate causal effects. We further examine the common claim that RWE provides greater external validity through more representative populations. Representativeness, however, is neither synonymous with scientific validity nor always necessary for informative inference. In many cases, the key question is not population-wide generalizability but the contextual applicability of estimates to specific decision settings. More broadly, all epidemiological study designs involve trade-offs among unbiasedness, precision, and generalizability. Randomized trials, observational studies, and quasi-experimental designs therefore occupy different positions along these methodological dimensions rather than constituting fundamentally different epistemic categories. Conclusion: We conclude that abandoning rhetorically charged labels such as RWE may promote greater conceptual clarity and encourage evaluation of evidence based on explicit methodological principles. (c) 2026 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Keywords:

Real-world evidence

Randomized controlled trials

Epidemiology

Research design

Scientific transparency

Representativeness

Randomized, controlled, and real

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