Framework for Real-World Data Used in Regulatory Submissions
Author(s)
Shivani Aggarwal, PhD, MS1, Barath Sukumar, MS2, Richard Thornton, BA3, David Goldfarb, PhD, MPH4.
1Landmark Science, Inc, Los Angeles, CA, USA, 2Landmark Science, Inc, San Diego, CA, USA, 3Landmark Science, Inc, East Windsor, NJ, USA, 4Landmark Science, Inc, New York, NY, USA.
1Landmark Science, Inc, Los Angeles, CA, USA, 2Landmark Science, Inc, San Diego, CA, USA, 3Landmark Science, Inc, East Windsor, NJ, USA, 4Landmark Science, Inc, New York, NY, USA.
Presentation Documents
OBJECTIVES: 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. Here we aim to present a framework for the use of RWD in regulatory decision-making.
METHODS: We evaluated 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 CDISC SDTM and ADaM. Additional measures include demonstrating data integrity from data accrual to analysis-ready datasets and ensuring adequate documentation of data transformations to support 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 (SDRG) and for ADaM tables (ADRG) should also be generated.
CONCLUSIONS: A structured framework for submitting observational data ensures transparency and compliance with regulatory guidelines. Sponsors and CROs 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 decision-making.
METHODS: We evaluated 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 CDISC SDTM and ADaM. Additional measures include demonstrating data integrity from data accrual to analysis-ready datasets and ensuring adequate documentation of data transformations to support 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 (SDRG) and for ADaM tables (ADRG) should also be generated.
CONCLUSIONS: A structured framework for submitting observational data ensures transparency and compliance with regulatory guidelines. Sponsors and CROs 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 decision-making.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
OP8
Topic
Organizational Practices
Topic Subcategory
Best Research Practices, Industry
Disease
No Additional Disease & Conditions/Specialized Treatment Areas