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P326: An AI-enabled Analysis of the Influence of Regulatory Commenting on FDA’s Real World Data/Real World Evidence Guidances

Poster Presenter

Susan Chong

Senior Manager, Global Regulatory Policy and Intelligence
Amgen
United States

Objectives

Highlight the importance and impact of regulatory commenting on select FDA Real-World Data (RWD)/ Real-World Evidence (RWE) guidance documents to promote more effective regulatory policies.

Method

FDA guidances on EHR, data standards, registries, and considerations for the use of RWD were included in this study. Utilized ChatGPT to extract and qualitatively summarize comments on the draft guidances which were analyzed to identify which comments FDA incorporated into the final guidances.

Results

Preliminary data show that the following recommendations were raised in the draft guidance dockets and subsequent actions were taken by FDA in the final guidances: Data Standards: - Expansion of FDA’s supported data standards beyond SDTM and ADaM o Partially incorporated. Although the final guidance only cites SDTM and ADaM as examples, and points to the data standards catalog, FDA is working on adopting new standards that meet FDA’s regulatory review needs as part of FDA’s Data Standards Program. - Public and transparent process for updating the Data Standards Catalog o Incorporated. Final guidance states that the Data Standards Catalog is periodically updated. FDA is accepting comments via the public docket. - Additional considerations for RWD mapping tools o Not incorporated. EHR: - Implement a risk-based approach to validation o Incorporated. FDA clarified that the selection of study variables for validation and the extent of effort required for validation depends on the necessary level of certainty and the implication of potential misclassification on study inference. - Efficient FDA-sponsor interactions to facilitate rapid evidence generation o Partially incorporated. After this draft guidance was issued, FDA launched the “Advancing RWE Program,” which outlines the content and format for meeting requests and a timeline. FDA also launched the CDER Center for RWE Innovation to promote inter-office communication. - Clarity on missing data and request for examples o Not incorporated. In addition, several stakeholders requested FDA to harmonize the RWE guidances for consistency and to align with EMA’s definitions. We are aware that global regulators are developing a new ICH guideline on RWE which may address these concerns. Due to character limitations, results from the Registries and RWD Considerations guidances will be provided on the poster.

Conclusion

Regulatory commenting is an important method to advance regulatory policy and to ultimately promote global regulatory harmonization. By providing clear and actionable feedback to regulators from various subject matter experts on guidance documents, stakeholders can communicate their views on policy issues that impact drug development in order to deliver innovative medicines to patients. This case study highlights the effectiveness of regulatory commenting when comments are feasible and practical. In addition, ChatGPT can serve as a helpful tool to assess changes in the policy environment. Although not all comments were directly incorporated into the final guidances, FDA addressed or plans to address stakeholder feedback through different avenues. For example, following the issuance of these guidances, FDA held a public workshop to address industry’s concerns and to promote the continued evolution and consistent application of RWD in drug development. Feedback also helped develop RWE-specific commitments as part of the Prescription Drug User Fee Act VII (e.g., FDA will convene a public workshop to discuss RWE case studies for post-approval study requirements). FDA also published an article containing examples of FDA approvals demonstrating how RWD can be utilized to generate RWE as part of a marketing application for regulatory decision-making (Rahman et al, 2024). Comments that weren't incorporated may have been too product-specific – necessitating a case-by-case approach – or outside the guidance’s scope. Nonetheless, there is value in raising concerns in comment submissions.