> ## Content Index
> Fetch the complete content index at: https://www.fdaweb.com/llms.txt
> Use this file to discover other available public pages before exploring further.

# Improving Cancer Trial Comparators: White Paper
- URL: https://www.fdaweb.com/improving-cancer-trial-comparators-white-paper/
- Published: 2025-10-30T12:00:00.000Z
- Updated: 2026-09-14T15:25:29.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5160131

A Friends of Cancer Research working group on determining a standard of care (SOC) comparator in multi-regional oncology trials says that while perfect solutions may not be attainable, “a thoughtful and ongoing process can improve applicability and transparency in comparator selection, ensuring trials remain feasible, meaningful, and representative across regions. In a new white paper, “Multi-Regional Clinical Trials: Addressing Standard of Care Variability,” the working group says the standard of care can vary widely across regions due to differences in regulatory approvals, clinical guidelines, real-world practice, access, and reimbursement. “It is often not a single treatment but a range of acceptable, context-dependent options that evolve over time as new evidence emerges…,” the group says.

The working group had representatives from FDA, drug companies, academia, and patient advocacy organizations

The paper lists these key considerations:

- comparator arms should reflect a clinically meaningful standard and not be inferior to therapies demonstrating clinical benefit;
- strategy for comparator selection and design should evaluate possible SOC evolution during trial planning and conduct;
- factors such as regulatory approvals, clinical guidelines, real-world use, feasibility, reimbursement, and patient and clinician preferences should all be considered; and
- balancing regional applicability, particularly in the U.S., with global feasibility is crucial, as SOC in one region may not be approved or practiced in another.

The paper suggests a guided approach to comparator selection through several proposed steps:

- clarify the target setting, reviewing disease, line of therapy, key jurisdictions, and trial purpose;
- identify plausible SOC options;
- screen for feasibility and ethical acceptability;
- assess timing and adaptation risks;
- engage regulators at early key milestones; and
- reassess periodically.

The working group concludes that “there are no universally applicable solutions for comparator selection in multi-regional clinical trials. The challenges created by evolving and heterogeneous SOCs are unlikely to be resolved by a single approach, and sponsors, regulators, and other stakeholders will need to pressure-test a range of strategies to identify workable paths forward. A shift toward totality of evidence approaches that integrate prospective trial data with contextual external data or descriptive analyses may offer a practical way to address evolving SOC landscapes without undermining the core trial design.”