Navigating Challenges and Seizing Opportunities: Leveraging Multiple RWD Sources in External Control Arms for HTA and Regulatory Decision-Making

ISSUE: In the absence of randomized controlled studies, especially for oncology and rare diseases, external control arms (ECA) using real world data (RWD) may be executed to provide context to single-arm trial findings in support of health technology assessment (HTA) and regulatory submissions. To address the challenge of limited sample size, multiple RWD sources such as chart reviews, electronic health record (EHR) databases, registries, and clinical trial extensions are increasingly utilized together to strengthen ECAs. Leveraging multiple RWD sources also offers valuable insights into treatment effects across diverse populations, geographies, data types, and timeframes. However, challenges persist in aligning trial criteria, treatment modalities, endpoints, and confounders across different data sources. As personalized medicine gains prominence and the demand for valid and successful ECAs grows, it is crucial to discuss the challenges and approaches to harmonizing multiple RWD sources for ECA creation.

OVERVIEW: This panel aims to explore how leveraging and harmonizing multiple RWD sources can enhance the evidentiary requirements of global HTA and regulatory bodies. Moderated by Dr. Chris Cameron, the panel will provide an overview of HTA/regulatory guidance documents on RWD/RWE sources and summarize recent ECA submission review results.

Key questions for the panelists include:

• What challenges and opportunities arise when harmonizing multiple RWD sources for creating ECAs in HTAs and regulatory submissions?
• How can we address emerging RWE guidance and enhance acceptance of ECAs by harmonizing multiple RWD sources?

International experts from RWE research organizations, industry sponsors, and academia/HTA reviewers will contribute their perspectives. Topics of discussion will encompass designing valid and transparent ECAs using multiple RWD sources, industry sponsors' experiences with ECAs, appropriate use of causal inference methods from academic viewpoints, and utilizing ECAs for risk-benefit assessment. The target audience includes HTA agencies, regulators, academics, patient advocacy organizations, and pharmaceutical/biotech manufacturers.

NOTE: There will be a discussion group on this topic following the session. Join us in the Discussion Lounge in Hall E North from 15:15-16:15 in Discussion Group B.