Global Inequalities in Clinical Trials Participation

Clinical trials shape medical evidence and determine who gains access to experimental therapies. Whether participation in these trials reflects the global burden of disease remains unclear. Here we analyze participation inequality across more than 62,000 randomized controlled trials spanning 16 major disease categories from 2000 to 2024. Linking 36.8 million trial participants to country-level disease burden, we show that global inequality in clinical trials participation is overwhelmingly shaped by country rather than disease burden. Country-level factors explain over 90% of variation in participation, whereas disease-specific effects contribute only marginally. Removing entire disease categories-including those traditionally considered underfunded-has little effect on overall inequality. Instead, participation is highly concentrated geographically, with a small group of countries enrolling a disproportionate share of participants across nearly all diseases. These patterns have persisted despite decades of disease-targeted funding and increasing alignment between research attention and disease burden within diseases. Our findings indicate that disease-vertical strategies alone cannot correct participation inequality. Reducing global inequities in clinical research requires horizontal investments in research capacity, health infrastructure, and governance that operate across disease domains.

💡 Research Summary

This paper investigates the global distribution of participation in randomized controlled trials (RCTs) from 2000 to 2024, encompassing 62,654 trials, 36.8 million participants, 16 disease categories, and 182 countries. By linking trial enrollment data to country‑level Global Burden of Disease (GBD) estimates, the authors compute a Participation‑to‑Burden Ratio (PBR) for each country‑disease pair, allowing a direct comparison of where disease burden resides versus where trial participants are recruited.

Descriptive maps reveal stark geographic and income‑based disparities: high‑income nations in North America and Western Europe dominate enrollment across virtually all disease areas, even when disease burden is concentrated elsewhere. For cardiovascular disease, regions with the lowest burden contribute the most participants; for HIV/AIDS, African nations bear 65 % of the burden yet contribute only 42 % of participants. Income‑stratified regressions show that high‑income countries exhibit a strong positive correlation between disease burden and trial enrollment (β = 0.466, p < 0.001), whereas low‑income countries display a weak correlation (β = 0.142, p = 0.012).

To determine whether inequality is driven by disease or by country, the authors employ several quantitative decompositions. First, they calculate a Contribution to Inequality Score (CIS) for each disease by measuring the change in the overall Gini coefficient when that disease’s trials are removed. All CIS values are tiny; the largest, cardiovascular disease, accounts for only 1.2 % of total inequality. Some traditionally under‑funded diseases (e.g., neglected tropical diseases) even have negative CIS, indicating they modestly reduce inequality.

Second, variance partitioning and Shapley value analysis attribute 93.5 % of the variance in PBRs to country‑level factors, 2.7 % to disease, and 3.8 % to temporal effects. Temporal decomposition shows that between‑disease inequality fell from 32 % (2000‑2004) to 22 % (2020‑2024), while within‑disease (i.e., geographic) inequality rose from 68 % to 78 %, confirming a shift toward country‑driven disparity.

Third, sensitivity analyses that remove the top 20 % of contributors demonstrate the asymmetry: eliminating the top 20 % of diseases reduces the Gini by only 0.4 %, whereas removing the top 20 % of countries (34 of 173) cuts the Gini by 23.9 % (from 0.884 to 0.672). Lorenz curves corroborate that country‑level concentration is the primary source of global inequality.

The authors argue that disease‑specific “vertical” funding initiatives—while valuable for targeted advances—cannot correct the structural imbalance because participation capacity is fundamentally anchored in national research infrastructure, regulatory environments, and health system strength. They propose a shift toward “horizontal” investments: building trial sites, strengthening ethical review boards, enhancing data management capacity, and improving overall health system governance across all disease domains, especially in low‑ and middle‑income countries.

In sum, the study provides robust empirical evidence that global clinical‑trial participation is overwhelmingly shaped by country‑level determinants rather than disease burden. Addressing this inequity will require coordinated, cross‑disease capacity‑building policies rather than further disease‑specific funding streams.