(C-124) Framework for Real-World Data Used in Regulatory Submissions

Background: The use of real-world evidence (RWE) for regulatory bodies and health technology assessment (HTA) decision-making has grown over the past decade. Numerous guidelines have been put forth by regulators and payors on the use of RWE in such submissions. Despite many best practice recommendations for RWE, a clear and comprehensive framework outlining the evidentiary requirements for real-world data (RWD) has not been well characterized.

Objectives: To present a framework for the use of RWD in regulatory decision-making.

Methods: We evaluated Food and Drug Administration (FDA) guidance documents on RWD/RWE in regulatory decision-making and evaluated recent case studies of RWE submitted in drug marketing authorization applications (MAAs). We examined RWD/RWE submitted in MAAs approved from January 2021-present. Publicly available documents were extracted, including FDA reports, and synthesized by two reviewers.

Results: We enumerated a framework for best practices in the submission of RWD in MAAs for regulatory decision-making. Key steps include submitting RWD electronically to support the contributing RWE and ensuring its conformance and transformation into FDA-accepted data standards such as the Clinical Data Interchange Standards Consortium (CDISC) standards Study Data Tabulation Model (SDTM) and Analysis Data Model (ADaM). Additional measures include demonstrating data integrity from data accrual to analysis-ready datasets and ensuring adequate documentation of data transformations to support quality control (QC) and regulatory audit trails. For each data standard such as SDTM and ADaM, data dictionaries should be completed. Further, sponsors should include Define files that contain metadata for the standardized datasets, along with controlled terminologies. A reviewer’s guide for the SDTM tables (Study Data Reviewer’s Guide) and for ADaM tables (ADaM Reviewer’s Guide) should also be generated.

Conclusions: A structured framework for submitting observational data ensures transparency and compliance with regulatory guidelines. Sponsors and research organizations should adhere to FDA-accepted data standards, include detailed metadata, traceable documentation, and have audit-ready processes. Maintaining data integrity and aligning with evolving regulatory requirements will enhance the use of RWE in regulatory decision-making.