Overcoming Challenges in Real-World External Control Arm Design

SUMMER 2022, THE EVIDENCE FORUM, WHITE PAPER

Summary

In certain circumstances, single-arm or randomized controlled trials (RCT) may require augmentation or supplemental data to fulfill evidence requirements for regulators and/or health-technology assessment (HTA) bodies. In such instances, external comparators (ECs) built from data generated from completed trials or during routine care can inform on disease natural history, support analyses that could not be conducted during clinical trials, enable comparative safety and/or efficacy, or provide context that improves the interpretation of the trial.

ECs designed to reflect patient care in routine clinical practice can be constituted from various sources of real-world data (RWD) such as electronic health record (EHR) databases and disease or product registries, or through bespoke data collection via medical record review or prospective cohorts. These real-world external control arms (RW-ECAs) are the focus of this article, which explores:

• Design factors for ECAs to ensure minimal bias and results reflective of the investigated clinical outcomes
• What to consider when selecting the right source of real-world data for your study
• Methodological challenges and regulatory considerations
• How RW-ECA supported a Phase III trial

Authors

Nahila Justo, MPhil, MBA, Senior Director, Nordic Database Analytics and Senior Research Scientist
Evidera, a business of PPD, part of Thermo Fisher Scientific

Mireia Raluy, MSc, Senior Director, Real-World Evidence – Europe
Evidera, a business of PPD, part of Thermo Fisher Scientific

Marielle Bassel, Director Research Science, Strategic and Scientific Affairs
Evidera, a business of PPD, part of Thermo Fisher Scientific

Katheryne Downes, PhD, MPH, Research Scientist, Strategic and Scientific Affairs
Evidera, a business of PPD, part of Thermo Fisher Scientific

Debra Schaumberg, ScD, OD, MPH, Vice President, Epidemiology and Head, Strategic and Scientific Affairs
Evidera, a business of PPD, part of Thermo Fisher Scientific