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

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.

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.

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).

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.