The Unregulated Majority: Who Ensures Quality in Non-HTA Real-World Studies?

Real-world evidence (RWE) is increasingly central to healthcare decision-making, with regulatory and health technology assessment (HTA) authorities formalising standards for data reliability, relevance, and transparency. Yet the vast majority of industry-sponsored RWE studies are not designed for submission to authorities. Instead, they are produced for scientific communication, disease awareness, medical education, or exploratory purposes. This “non-submission RWE” dominates the evidence ecosystem but often proceeds without prespecified protocols, adequate comparators, or peer-reviewed oversight. The result is a body of evidence that appears scientific but lacks safeguards against bias, selective reporting, and promotional drift. This commentary examines recurring flaws in non-submission RWE, including protocol shortcuts, descriptive overreach, weak peer review, and selective dissemination. It highlights the risks these shortcomings pose for clinicians, patients, and policymakers by distorting perceptions of treatment value and eroding trust in RWE as a credible scientific field. Drawing on regulatory pilots, harmonisation efforts, and methodological innovations such as target trial emulation and transparency templates, it argues that the tools to improve quality already exist but remain underused in non-submission contexts. A pragmatic framework is proposed around three pillars: protocol registration, analytical transparency, and internal governance boards. These measures, adapted from existing regulatory and trial practices, would raise the floor of quality across all RWE. Extending accountability to non-submission studies is not a compliance burden but a professional responsibility. If real-world data are to guide real-world decisions, all studies—regulatory or not—must meet baseline standards of validity, transparency, and integrity.