Diversity and inclusivity in clinical trial populations for maintenance inhaler therapy in people with COPD: a systematic review

Introduction Social determinants of health (SDH) influence chronic obstructive pulmonary disease (COPD) prevalence, progression, and treatment, yet their inclusion in clinical trials is poorly understood. This study examined recruitment strategies for diverse populations in COPD trials of long-acting muscarinic antagonists (LAMA) and/or long-acting beta agonists (LABA), with or without additional therapy including inhaled corticosteroids (ICS) and assessed SDH reporting in primary trial documents and publications. Methods Four clinical trials databases (CENTRAL, Clinicaltrials.gov, ISRCTN and ANZCTR) were searched to identify LAMA and/or LABA clinical trials with or without ICS in adults with COPD registered between 01/01/2000 and 08/05/2023. Extracted data included: study locations, recruitment strategies, study outcomes, eligibility criteria, participant demographics and subgroup analyses. Results 1822 records were identified, with 491 primary trials included. Of these, 407 trials (256 271 participants) had results available, and 341 trials had associated publications. 439 trials (89.4%) were completed. Age (n=387, 95.1%) and sex (n=386, 94.8%) were well reported, with a male preponderance (n=176 285, 68.8%). Inclusion of women improved from 22.6% (2006) to 46.5% (2020). Ethnicity was reported in 209 (51.4%) trials, with over-representation of White individuals (n=130 086, 83.2%) and no change over time. Only one trial reported socioeconomic status or occupation; none reported education or rurality. Most trials (97.5%) were conducted in high/upper-middle-income countries. Conclusions SDH, other than age and sex, were under-reported in LABA/LAMA COPD trials, and when reported, demonstrated a longstanding lack of diversity. Extrapolating efficacy from narrow populations may risk suboptimal care for diverse groups. Future trials must include and report on diverse populations to demonstrate safety and efficacy for all people in all contexts.