Overcoming Challenges in Real-World External Control Arm Design

Overcoming Challenges in Real-World External Control Arm Design

Single-arm or randomized controlled trials (RCTs) sometimes need additional data to meet regulatory and health technology assessment (HTA) requirements. External comparators (ECs), derived from completed trials or routine care data, can provide insights into disease history, support analyses not possible in trials, and enable comparative safety and efficacy evaluations. ECs, reflecting routine clinical practice, can be sourced from real-world data (RWD), such as electronic health records (EHR) and disease registries, or through bespoke data collection. This article focuses on real-world external control arms (RW-ECAs), discussing design factors to minimize bias, considerations for selecting RWD sources, methodological challenges, regulatory considerations and how RW-ECAs supported a Phase III trial.

Authors:

• Nahila Justo, MPhil, MBA, senior director and senior research scientist
• Mireia Raluy, MSc, senior director, real-world evidence – Europe
• Marielle Bassel, director, research science, strategic and scientific affairs
• Katheryne Downes, Ph.D., MPH, research scientist, strategic and scientific affairs
• Debra Schaumberg, ScD, OD, MPH, vice president, epidemiology and head, strategic and scientific affairs