Overview
Hematology and oncology trials have undergone rapid globalization, shifting from academic centers in high-income countries to hundreds of sites across diverse regions worldwide.
While globalization potentially accelerates enrollment, increases accessibility, and broadens market access, it can paradoxically alter relative participation among different regions. Underrepresentation of populations in clinical trials based on race and regional imbalances can mar the generalizability of findings.
How has globalization altered geographic representation in pivotal cancer trials, and is North America's patient contribution disproportionately less relative to its site representation?
Key Findings
High-Income Countries
HICs comprised 77% of all trial sites but enrolled only 65% of patients (P < 0.0001). Contribution was disproportionately low relative to site representation.
US/Canada Specifically
US/Canada constituted 24.3% of all sites but contributed only 15.6% of patients -the largest disparity of any region (P < 0.0001).
Asia Over-Contributing
Asia comprised 24% of sites but enrolled 35% of patients -contributing more patients relative to their site representation.
Subgroup Analysis
Only 36% of global trials that reported geographic distribution performed subgroup analysis of primary endpoint based on region.
Regional Breakdown
Analysis of site representation versus patient contribution across major regions:
| Country/Region | Sites | Patients | Disparity | P-value |
|---|---|---|---|---|
| North America (US/Canada) | 23.5% | 15.9% | -7.6% | < 0.001 |
| Europe | 49.3% | 47.0% | -2.3% | 0.010 |
| Australia | 3.2% | 2.2% | -1.0% | < 0.001 |
| Asia | 24.0% | 35.0% | +11.0% | < 0.001 |
Trial Characteristics
90% of trials were global in nature, run across a median of 16 countries (range: 2-38) involving a median of 114 sites (range: 1-597). The number of sites in participating HICs was significantly higher than others (median: 25 vs 16; P = 0.008).
Methods
I conducted a systematic review of all Hematology and Oncology FDA drug approvals between June 2022 and June 2025:
Data Source Identification
FDA approvals were identified using the publicly available Hematology/Oncology Approvals and Safety Notifications archive. Primary reports obtained from PubMed and ClinicalTrials.gov.
Variable Extraction
Extracted key variables including drug name, approval type, phase, sponsor, trial design, duration, number of sites, participating countries, total enrollment, and patient demographics by race and country.
Income Classification
Global enrollment was analyzed by country income classification per World Bank classification and region to assess trial diversity and representation.
Statistical Analysis
Used descriptive statistics and Fisher exact test to evaluate proportional global representation and identify disproportionate participation between income groups.
Standardized Methodology
Developed standardized methodology using ClinicalTrials.gov to ensure data consistency. Trials without full publications or clinical registry entries were excluded from analysis.
Why This Matters
The FDA has recently emphasized US representation in clinical trials. Drug applications have had unfavorable outcomes for failing to meet this standard. Understanding these trends is critical for ensuring equity and generalizability of research.
Generalizability of Results
When populations are underrepresented in clinical trials, findings may not be generalizable to the broader patient population who will ultimately receive these treatments.
Regulatory Implications
The FDA's emphasis on US representation means trials with disproportionate enrollment may face regulatory challenges during the approval process.
Health Equity
Systematic exclusion of certain populations from cutting-edge treatments perpetuates health disparities and limits access to innovative therapies.
Scientific Efficiency
Missing genetic diversity that could reveal important treatment variations reduces the scientific value of trials and may miss population-specific effects.
Plain Language Summary
Clinical trials for cancer drugs are performed worldwide. While this increases accessibility to research globally, it's not clear how this has affected participation of individual countries. We found that nearly half of trials don't report patient contribution by region, and high-income countries like US/Canada contribute fewer patients than expected based on their number of trial sites. With globalization, it's important to ensure patients across the world are well represented so that results are generalizable to the population.
Mentorship
Dr. Kanwal Raghav, MD
Gastrointestinal Medical Oncology, MD Anderson Cancer Center
Dr. Raghav's guidance was instrumental in developing the research methodology and interpreting the clinical significance of our findings. His expertise in oncology clinical trials provided essential context for understanding global trial dynamics.