SW-4F - Approaches to Time-Zero and Time-Related Bias in External Control Arm Study Design: Methodological Considerations and Applications

Background: There is a growing interest in utilizing external control arm (ECA) study designs in comparative effectiveness research, particularly in rare diseases or areas with unmet medical needs. When ECAs are sourced from real-world data (RWD), careful methodological considerations are needed to avoid time-related biases, particularly in situations when the calendar time is not aligned between treatment arms. Additionally, selecting the most appropriate time-zero presents a unique challenge, as multiple eligibility time points may exist within RWD, necessitating careful study design to ensure valid and unbiased comparisons.

Objectives: This symposium will explore methodological approaches for addressing time-related biases and selecting an appropriate time-zero in external control arm (ECA) studies. Through case studies, participants will gain insights into practical solutions for mitigating these biases in real-world applications. Additionally, the session will provide an overview of ECA study designs, key methodological considerations, and relevant terminologies to ensure a comprehensive understanding from the audiences.

Description: This symposium will be moderated by Profs. Ju-Young Shin and Kenneth Man, who will provide an overview of ECA using RWD and introduce three presentations.
(1) Time-related bias in studies using historical controls (Prof. Samy Suissa)
This presentation will discuss methodological challenges and solutions for mitigating time-related bias in studies using historical controls (20 mins).
(2) Time zero selections and their impact on non-interventional studies (Prof. Laurent Azoulay)
This presentation will discuss different approaches for selecting time-zero and their impact on non-interventional studies, focusing on the potential biases associated with each approach (20 mins).
(3) ECA studies with multiple potential eligibility time points (Dr. Ju Hwan Kim)
This presentation will discuss current challenges in selecting time-zero in ECA with multiple potential eligibility time points, accompanied by case studies for evaluating effectiveness of chimeric antigen receptor T-cell therapies (20 mins).
(4) Panel discussion and Q&A session
The symposium will conclude with a guided panel discussion featuring all speakers, followed by a Q&A session (20 min).