12/29/2025
How can global cancer trials be designed when the standard of care (SOC) differs in every region and may change while new patients enroll?
Multi-regional clinical trials (MRCTs) in oncology face a central challenge: SOC can widely vary across regions due to differences in regulatory approvals, clinical guidelines, real-world practice, and access. These differences create tension between regional applicability, particularly for U.S. regulators, and global feasibility. The situation becomes even more complex when new therapies emerge mid-trial, potentially undermining clinical equipoise and enrollment.
Our white paper, “Multi-Regional Clinical Trials: Addressing Standard of Care Variability,” explained a structured "funnel approach" to comparator selection that progressively filters the broad landscape of potential SOCs into a justified, feasible choice. This seven-step framework guides sponsors through clarifying the target setting, identifying plausible SOC options, screening for feasibility and ethical acceptability, prioritizing regional applicability, assessing timing and adaptation risks, engaging regulators early, and reassessing periodically during trial conduct.
Comparator discussions are best addressed during the pre-phase 3 meeting with the FDA, when trial design can still be meaningfully influenced. Once a study is underway, implementing mid-trial changes is rarely feasible—protocol amendments can take six months to a year to operationalize across global sites. This structured process helps ensure comparator selection remains scientifically justified, ethically sound, and operationally feasible, while supporting transparency and consistent dialogue across sponsors, regulators, and patients.
Read the full white paper to explore the complete framework, practical scenarios, design strategies, and critical considerations for successful MRCT comparator selection: https://friendsofcancerresearch.org/wp-content/uploads/Multi-Regional-Clinical-Trials-Addressing-Standard-ofCare-Variability.pdf.
