AUTHOR=Facile Rhonda , Chronaki Catherine , van Reusel Peter , Kush Rebecca TITLE=Standards in sync: five principles to achieve semantic interoperability for TRUE research for healthcare JOURNAL=Frontiers in Digital Health VOLUME=Volume 7 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/digital-health/articles/10.3389/fdgth.2025.1567624 DOI=10.3389/fdgth.2025.1567624 ISSN=2673-253X ABSTRACT=The effective and meaningful exchange of data is pivotal for patient care, informed decision-making, and advancements in research and technology. This opinion piece explores the critical role of semantic interoperability (SI) in ensuring meaningful health data sharing across diverse systems. Emphasizing the imperative of synchronizing the use of data standards, we address the challenges posed by disparate data formats and underscore the impact on patient outcomes. International, harmonized standards are presented as a cornerstone for achieving SI, while the drawbacks of proprietary standards are examined. Case studies, including the complementary use of International Organization for Standardization (ISO), Health Level Seven Fast Healthcare Interoperability Resources (HL7 FHIR), and Clinical Data Interchange Standards Consortium (CDISC) standards, offer practical insights. We offer here five simple principles [reuse existing standards where possible, avoid mapping, implement standards at the start of a project, participate in standards development activities with standards development organizations (SDOs), and work toward harmonization of standards across SDOs] for achieving semantic meaning in support of Trustworthy, Reusable, Understandable data Elements (TRUE) research data for healthcare. We hope to provide a view to a future where standards are in sync and the proposed five principles are deployed globally to ensure the conduct of trustworthy research for the sake of improving health outcomes for all.