Trial characteristics associated with under-enrolment of females in randomized controlled trials of heart failure with reduced ejection fraction: a systematic review

Sera Whitelaw, Kristen Sullivan, Yousif Eliya, Mohammad Alruwayeh, Lehana Thabane, Clyde W. Yancy, Roxana Mehran, Mamas A. Mamas, Harriette G.C. Van Spall*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

5 Scopus citations

Abstract

Aims: To 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 results: We 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. Conclusions: Females 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.

Original languageEnglish (US)
Pages (from-to)15-24
Number of pages10
JournalEuropean Journal of Heart Failure
Volume23
Issue number1
DOIs
StatePublished - Jan 2021

Keywords

  • Enrolment
  • Heart failure
  • Randomized controlled trials
  • Sex and gender

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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