On September 16, 2024, the U.S. Food and Drug Administration (FDA) issued draft guidance aimed at improving the conduct of multiregional clinical trials (MRCTs) in oncology, addressing an urgent need to enhance the relevance and applicability of cancer research findings to diverse patient populations.
FDA’s draft guidance on MRCTs in oncology will change approaches to cancer research
MRCTs are critical in evaluating treatment effectiveness and safety across various geographic regions under a unified protocol. However, the FDA has expressed concern over the declining participation of U.S. patients in these trials, which may compromise the applicability of results to American healthcare standards.1,2
- This draft guidance emphasizes inclusivity and diversity within clinical trials. It calls for sponsors to prioritize the inclusion of historically underrepresented groups—such as Black, Hispanic/Latino, Indigenous, Asian, and female populations—ensuring that research findings are generalizable across different demographics.3,4
- The guidance highlights the importance of regional data analysis. FDA is urging sponsors to specify methods for evaluating treatment effects in various populations, which is crucial for developing effective cancer therapies tailored to the needs of all patients.1,4
The guidance also acknowledges some significant challenges, including healthcare access disparities that may hinder participation from diverse populations.
FDA Commissioner Robert Califf has noted that the guidance is intended to be a starting point for dialogue, emphasizing the need for flexibility and ongoing stakeholder engagement to refine these recommendations and achieve meaningful representation in clinical trials.3,5
While FDA sets clear expectations for global trial conduct, implementing these requirements effectively requires experienced partners who understand both regulatory demands and operational realities.
At Precision for Medicine, we've been anticipating and preparing for this direction, addressing the three key areas that the FDA has identified as crucial for successful MRCTs.
Cancer doesn’t respect borders — neither should our clinical trials
There’s an urgent need to rethink how we conduct global research while ensuring results remain relevant for American patients. The FDA’s new guidance addresses this challenge head-on. The guidance focuses on five key areas that will reshape how we approach cancer research.
I. Standardization in MRCT Trial Design Across Regions
Rather than letting each region interpret protocols differently, the FDA envisions a unified approach that maintains flexibility where it matters most. This means implementing consistent methodologies while acknowledging that healthcare systems vary significantly across borders.II. Importance of Cultural Adaptations in Global Oncology Trials
A treatment protocol that works perfectly in Boston might need subtle adjustments in Bangkok or Berlin. The FDA recognizes this reality and encourages thoughtful adaptation without compromising scientific rigor. For instance, a trial might adjust its patient monitoring schedule to account for different healthcare delivery systems while maintaining strict endpoint measurements.III. Navigating Regulatory Compliance Across Borders
Instead of forcing research teams to navigate different requirements blindly, the guidance provides a framework for harmonizing ethical and regulatory practices across regions. This could slash redundant paperwork while maintaining high standards of patient protection.
IV. Inclusion of diverse sites
Considering the varying standards of care across different regions, the range of sites may broaden to encompass community hospitals and primary healthcare centers. Researchers must be prepared to equip these sites and ensure they are ready for audits.
V. Analysis protocols that factor in regional variations
Regional treatment effects should be estimated, and the method for analyzing geographical regional effects should be pre-specified. The guidance suggests that MRCTs do not need to be powered to evaluate efficacy specifically within the U.S. subgroup. However, the FDA requires a sufficient number of U.S. patients to enable robust subgroup analyses.
What FDA MRCT guidelines means for the future of oncology clinical research
Artificial intelligence will likely play an increasing role in adapting protocols across regions while maintaining scientific integrity. Real-time data harmonization tools are already emerging, promising to streamline the process further. But technology alone isn’t the answer.
Success will require a fundamental shift in how we think about global research. Cultural competency becomes as important as scientific expertise. Research teams need to understand not just the science of cancer but also the diverse contexts in which it occurs.
Precision for Medicine’s approach to FDA-compliant MRCTs
Successful MRCTs require more than just compliance. Precision for Medicine delivers global regulatory expertise, expert operational teams, and proprietary data investigation technologies to ensure that each trial site—regardless of location—adheres to the highest standards of data integrity.
As the industry adapts to FDA’s guidance, the key challenge will be striking the right balance between standardization and flexibility, allowing scientific rigor to thrive without losing sight of regional differences.
Success will require commitment, investment, and a willingness to embrace new ways of working. But the potential reward—faster development of effective cancer treatments for patients worldwide—makes it worth the effort.
Discover the ways this guidance might impact your upcoming clinical program.
References
- "FDA Draft Guidance on Conducting Multiregional Oncology Clinical Trials." The ASCO Post, September 2024. https://ascopost.com/news/september-2024/fda-draft-guidance-on-conducting-multiregional-oncology-clinical-trials/.
- "FDA Issues Draft Guidance on Conducting Multiregional Clinical Trials in Oncology." U.S. Food and Drug Administration, March 2024. https://content.govdelivery.com/accounts/USFDA/bulletins/350b816.
- "FDA Issues Draft Guidance on Conducting Multiregional Clinical Trials in Oncology." PR Newswire. https://www.prnewswire.com/news-releases/fda-issues-draft-guidance-on-conducting-multiregional-clinical-trials-in-oncology-302249082.html.
- "FDA Just Published Its Diversity Action Plan Guidance—Here’s What You Need to Know." Friends of Cancer Research. https://friendsofcancerresearch.org/news/agencyiq-fda-just-published-its-diversity-action-plan-guidance-heres-what-you-need-to-know/.
- "Challenges in FDA’s Multiregional Clinical Trials Guidance." Applied Clinical Trials. https://www.appliedclinicaltrialsonline.com/view/challenges-fda-multiregional-clinical-trials-guidance.
