Underrepresentation of Women in COPD Pharmacologic Trials Relative to Disease Burden: A Systematic Review and Meta-Analysis.

Abstract

<h4>Background</h4>Although chronic obstructive pulmonary disease (COPD) increasingly affects women, they remain under-represented in randomized controlled trials (RCTs). Understanding enrollment patterns is essential to ensure the generalizability of COPD therapeutic evidence.<h4>Methods</h4>We systematically identified RCTs of pharmacologic interventions for COPD published between 2010 and 2024. For each trial, we calculated the Enrollment Disparity Difference (EDD)-defined as the trial's percentage of women minus the Global Burden of Disease (GBD) sex-specific prevalence. Random-effects meta-analyses were conducted to pool EDD across trials; heterogeneity was explored using subgroup analyses (region, sample size, therapy class, age group, funding source) and meta-regression models. Temporal trends were evaluated, and a weighted annual EDD trajectory with forecasted values through 2026 was generated.<h4>Results</h4>A total of 190 RCTs were included. Women comprised 31.7% of enrolled participants. Pooled EDD was -0.21 (95% CI, -0.22 to -0.19), indicating relative underrepresentation. Heterogeneity was very high (I² = 100%). Underrepresentation varied significantly across regions, with the greatest gaps observed in Asia and Africa and the smallest in North and South America. Age was a significant moderator (β = -0.0070 per year, p = 0.0006), with greater disparities in trials enrolling older patients. Industry funding, sample size, and therapy class were not significant predictors. A continuous-year meta-regression demonstrated an improvement in female representation over time (β = 0.0068 per year, p = 0.0269).<h4>Conclusion</h4>Women remain underrepresented in COPD RCTs. Although modest improvements have occurred, significant gaps persist. Ensuring equitable representation is essential for generating evidence that reflects the COPD population.