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 trial participation is overwhelmingly structured by country rather than disease. 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.

翻译：临床试验塑造医学证据并决定谁能获得实验性疗法。这些试验的参与是否反映全球疾病负担仍不明确。本文分析了2000年至2024年间跨越16个主要疾病类别的62,000多项随机对照试验中的参与不平等现象。通过将3,680万试验参与者与国家层面的疾病负担数据关联，我们发现临床试验参与的全球不平等性主要由国家而非疾病因素决定。国家层面因素解释了超过90%的参与差异，而疾病特异性影响微乎其微。即使剔除包括传统认为资金不足的疾病在内的整个疾病类别，对总体不平等的影响也极小。相反，试验参与在地理上高度集中，少数国家在几乎所有疾病中都招募了不成比例的参与者。尽管经过数十年的疾病定向资助以及研究关注度与疾病负担之间日益协调，这些模式依然持续存在。我们的研究结果表明，仅靠疾病纵向策略无法纠正参与不平等问题。减少临床研究中的全球不平等需要在研究能力、卫生基础设施和跨疾病领域的治理方面进行横向投资。