Developing Fit-for-Purpose External Control Arms to Optimize Submissions to Regulatory and Health Technology Assessment Agencies

When researchers use existing data to contextualize the results of single-arm trial data, it is called an external control arm (ECA). ECAs may be appropriate when recruiting an adequate number of patients is difficult or impossible, such as for trials in rare and/or imminently life-threatening conditions. However, when using real-world data (RWD) to populate an ECA, the burden is on researchers to demonstrate the appropriateness of the data and methodology. Regulatory and health technology assessment (HTA) agencies have been critical in their feedback on previous ECA submissions, citing concerns about the validity of evidence from RWD, including confounding and selection bias. Recognizing these issues, the US Food and Drug Administration (FDA) released a draft guidance in February 2023 highlighting key agency considerations when assessing whether the real-world evidence (RWE) generated from ECAs is fit-for-purpose.

In this session, senior experts in epidemiology and biostatistics will discuss their perspectives on best practices and first-hand experiences with ECAs.

Learning Objectives:

• Describe the framework for using RWD to enable a comparison group for a single-arm clinical trial.
• Understand key regulatory and HTA agency concerns regarding the methodological challenges to ECAs, including data selection, patient identification, confounding and bias, and standardized reporting of outcomes.
• Explore the pathways to early engagement with regulatory and HTA agencies to assess the suitability of ECA methods to complement a clinical trial program in support of drug approval.

Seating is limited.

Sponsor: Genesis Research