Global Trials, Local Relevance: A Scientific and Regulatory Framework for Regional Enrollment in Cancer Drug Development.

Overview

abstract

PURPOSE: Global oncology trials face increasing scrutiny over regional enrollment imbalances, as regulatory agencies such as the US Food and Drug Administration, European Medicines Agency, and Pharmaceuticals and Medical Devices Agency demand data reflective of population diversity. This push is grounded in evidence that genetic polymorphisms (eg, UGT1A1*28, CYP2D6), human leukocyte antigen-related toxicities, and biomarker prevalence (eg, epidermal growth factor receptor mutations in approximately 15% of Western v approximately 50% of Asian patients with lung cancer) can significantly influence treatment outcomes. METHODS: We reviewed scientific literature, regulatory case studies, and methodological innovations addressing regional heterogeneity in oncology trials. Particular focus was given to statistical tools such as adaptive randomization for real-time enrollment balancing, Bayesian hierarchical models for data borrowing across regions, and Multi-Regional Clinical Trial designs for structured consistency assessments. Control arm variability because of regional differences in standard of care and drug access was also examined. RESULTS: Recent regulatory setbacks, especially involving Asia-centric trials, underscore the consequences of insufficient regional planning. Emerging statistical approaches, including adaptive and Bayesian methods, show promise in managing heterogeneity while preserving trial integrity. Persistent challenges include disparities in trial infrastructure, molecular subtype distributions, and comorbidity patterns. Broader regional inclusion and integration of real-world evidence are increasingly critical to overcoming these limitations. CONCLUSION: Regional enrollment should be viewed not as a regulatory formality, but as a scientific and ethical priority. The future of global oncology trials hinges on proactive regional planning, innovative methodology, and cross-sector collaboration. Aligning global efficiency with local relevance can enhance scientific robustness, support regulatory alignment, and expand equitable access to novel cancer therapies worldwide.