Project Summary/Abstract The use of electronic health record (EHR) systems as a source of “real-world data” (RWD) has great potential to transform and improve research. Despite the potential value and public health need for RWD, the ability to extract and use data from EHR systems for research is limited due to the absence of clearly defined and uniformly implemented standards that represent the semantic meaning of clinical data, including the context and specificity of coding. A particular challenge is that clinical coding systems used for EHR data often have very granular codes to support documentation of detailed diagnoses and highly specific tests and packaged medications. These granular codes must be grouped into broad concepts for research analyses and submissions, but consistent and reproducible data aggregation methods that preserve important semantic meaning and context of clinical RWD for research purposes are lacking. We propose to use a well-informed environmental scan, targeted literature review, and a multi-stakeholder group of standards experts to identify unresolved methodological issues and critical challenges – and delineate alternative approaches for standardization or harmonization - that can support strategic action for leveraging RWD in the short term and enable a more robust clinical research infrastructure to support future research needs. The multi-stakeholder group will include data and standards experts from both clinical informatics and research data standards communities.