Global disparities in access to randomized controlled trials for pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a rare and life-threatening pulmonary vascular disease. Randomized clinical trials (RCTs) have been crucial in developing pharmacological therapies for PAH, but the global geographic distribution of PAH clinical trials has not been systematically characterized and may highlight disparities in access to clinical research. Analyzing patterns of trial availability may elucidate disparities in global research infrastructure in PAH and access to novel therapies. This study was a systematic review and cross-sectional analysis of randomized, parallel-group phase II, phase III, or combined phase II/III trials of pharmacological interventions in adults with PAH registered on ClinicalTrials.gov from inception through February 2026. RCT access was determined using recruiting locations reported on ClinicalTrials.gov. Countries and recruiting sites were classified according to United Nations geographic regions and continents. Country-level demographic and development indicators, such as population size, PAH prevalence, urban population percentage, Healthcare Access and Quality (HAQ) Index, Socio-demographic Index (SDI), and World Bank Income classification, were linked to country-level trial counts and recruiting-site counts. Associations between country characteristics and PAH trial counts and recruiting-site counts were evaluated using negative binomial regression models. A total of 294 clinical trials were identified, of which 97 RCTs met inclusion criteria. Most trials and recruiting sites were in North America and Europe. Many countries across Africa, Central Asia, and parts of South America had little or no representation in PAH clinical trials. In adjusted models, each one-unit increase in Healthcare Access and Quality (HAQ) Index was associated with a 5.2% increase in the expected number of phase II trials (β=0.051, 95% CI 0.016-0.089; p=0.006). For phase III trials, each one-percentage-point increase in urban population was associated with a 2.7% increase in expected trial count (β=0.027, 95% CI 0.011-0.043; p<0.001), and each one-unit increase in HAQ Index was associated with a 4.0% increase (β=0.039, 95% CI 0.013-0.066; p=0.003). Similar associations were observed for recruiting-site counts. Greater healthcare system capacity and urbanization were associated with increased PAH trial counts and recruiting-site counts, highlighting persistent geographic disparities in clinical research access. PROSPERO registration number CRD420261298884.