Trial characteristics associated with under‐enrolment of females in randomized controlled trials of heart failure with reduced ejection fraction: a systematic review
Journal Articles
Overview
Research
Identity
Additional Document Info
View All
Overview
abstract
AbstractAimsTo evaluate temporal trends in the enrolment of females in randomized controlled trials (RCTs) of heart failure with reduced ejection fraction (HFrEF) published in high‐impact journals, and assess RCT characteristics associated with under‐enrolment.Methods and resultsWe searched MEDLINE, EMBASE and CINAHL for studies published from January 2000 to May 2019 in journals with impact factor ≥10. We included RCTs that recruited adults with HFrEF. We used a 20% threshold below the sex distribution of HFrEF to define under‐enrolment. We used multivariable logistic regression to assess trial characteristics independently associated with under‐enrolment. We included 317 RCTs. Among the 183 097 participants, mean (standard deviation) age was 63.0 (7.0) years and 25.5% were female. Females were under‐enrolled in 71.6% [95% confidence interval (CI) 66.6–76.6%] of the RCTs; enrolment did not increase significantly between 2000–2019. Sex‐related eligibility criteria [odds ratio (OR) 2.05, 95% CI 1.01–4.16; P = 0.046]; recruitment in ambulatory settings (OR 2.56, 95% CI 1.37–4.81; P = 0.003); trial coordination in North America (OR 4.44, 95% CI 1.09–18.07; P = 0.037), Europe (OR 6.79, 95% CI 1.63–27.39; P = 0.018) and Asia (OR 9.33, 95% CI 1.40–12.40; P = 0.033); drug (OR 1.76, 95% CI 1.96–7.36; P < 0.001) and device/surgical interventions (OR 1.69, 95% CI 1.16–9.43; P = 0.002); and men in first and last authorship position (OR 1.32, 95% CI 1.12–3.54; P = 0.047) were associated with under‐enrolment of females.ConclusionsFemales were under‐enrolled relative to disease distribution in a majority of high‐impact HFrEF RCTs, with no change in temporal trends between 2000 and 2019. Trial characteristics and gender of trial leaders were associated with under‐enrolment.
