Clinical Researcher—October 2026 (Volume 40, Issue 5)
PEER REVIEWED
Patricia Fitzgerald, MS
Women remain persistently underrepresented in coronary artery disease (CAD) clinical trials, limiting the generalizability of evidence used to guide cardiovascular care. Despite increased regulatory attention and professional awareness, sex-balanced enrollment has not been consistently achieved.
This article synthesizes evidence from randomized controlled trials evaluating patient-centered and mechanistic interventions in CAD populations to examine patterns of female participation and identify operational contributors to ongoing disparities. Across studies, female enrollment varied widely, with higher representation observed in education-based and supportive care interventions and lower representation in pharmacologic or mechanistic trials.
These patterns appear driven less by patient willingness and more by eligibility criteria, visit burden, recruitment design, and delayed corrective action during trial conduct. Findings are translated into actionable, role-specific strategies for clinical research professionals involved in feasibility assessment, recruitment oversight, monitoring, and site management.
Why This Matters to Clinical Research Professionals
Cardiovascular disease is the leading cause of death among women globally, yet women continue to be underrepresented in CAD clinical trials.{1–4} This imbalance limits external validity and perpetuates sex-based disparities in diagnosis and treatment. While awareness has grown, enrollment practices, particularly in late-phase pharmacologic and mechanistic studies, have changed slowly.{4}
For clinical research professionals, under-enrollment of women is fundamentally an operational issue shaped by protocol design, feasibility assumptions, recruitment planning, and oversight decisions made throughout the trial lifecycle.
Background
Historically, cardiovascular trials disproportionately enrolled male participants due to misconceptions about disease prevalence and concerns related to pregnancy and hormonal variability.{1,3} Although these assumptions have been challenged, their influence persists in eligibility criteria and trial conduct. Regulators and professional organizations now emphasize representative enrollment, yet progress in CAD trials remains uneven. Clinical research associates (CRAs), coordinators, investigators, and site leaders are positioned to address these gaps by identifying and correcting operational barriers.
Purpose and Article Type
This manuscript is a practice-oriented operational perspective informed by a targeted narrative review (qualitative synthesis) of selected randomized controlled trials in adult CAD populations. It is not intended as a formal systematic review; rather, it uses illustrative trials to identify enrollment patterns and translate them into practical, role-specific actions for clinical research professionals.
Methods Overview
A structured search of PubMed and CINAHL was conducted between November 1, 2020, and November 1, 2025, using combinations of terms including coronary artery disease, women, sex differences, randomized controlled trial, enrollment, and participation. Studies were eligible if they were peer-reviewed randomized controlled trials enrolling adults with CAD and reported participant sex distribution and clinical, physiologic, or quality-of-life outcomes.
Studies were excluded if they did not report sex distribution, were not randomized trials, focused on non-CAD cardiovascular conditions, or were non-English publications. Titles and abstracts were screened followed by full-text review.
Five trials met inclusion criteria. Due to heterogeneity in interventions and outcomes, findings were synthesized qualitatively with attention to operational features influencing enrollment.
Key Findings
Female enrollment ranged from approximately 20% to more than 80% across trials, reflecting inconsistent enrollment strategies.{4} Pharmacologic and mechanistic studies enrolled the lowest proportions of women, while education-based and supportive care trials achieved higher representation.{5,9}
Trials incorporating nurse-led education, self-care frameworks, or mobile health tools often reduced visit burden and enabled flexible engagement.{5,9} Studies requiring intensive in-person assessments and rigid schedules consistently enrolled fewer women.{6,7} Importantly, even trials with higher female participation frequently lacked sufficient numbers to support robust sex-specific analyses.
Why Enrollment Imbalances Persist
Persistent under-enrollment of women appears driven primarily by operational decisions rather than patient unwillingness. Restrictive eligibility criteria, exclusion related to pregnancy or comorbidities, rigid visit schedules, and feasibility assumptions that underestimate caregiving and work responsibilities disproportionately affect women.{2,4}
Pharmacologic and mechanistic trials often require intensive in-person assessments and narrowly defined populations, amplifying these barriers. While these constraints are typically identifiable early, they are frequently treated as static limitations rather than dynamic risks requiring timely corrective action.
Prescriptions for Translating Evidence into Action
Study Coordinators
Maintain screening and enrollment logs stratified by sex, identify early imbalances, tailor recruitment messaging to reflect women’s symptom experiences, and proactively offer flexible scheduling or remote visit options when allowable by protocol.
CRAs/Study Monitors
Treat sex-based enrollment imbalance as a quality and feasibility risk. Review enrollment trends early and often, document barriers, escalate concerns promptly, and collaborate with sites and sponsors on corrective actions such as protocol clarifications or recruitment adjustments.{2,4}
Investigators
Advocate for prespecified sex-based enrollment targets during protocol development, reassess exclusion criteria for unintended bias, and support adaptive recruitment plans if enrollment skews early.
Study Site Leadership
Incorporate enrollment equity into feasibility assessments, training, and quality oversight. Allocate resources to support flexible visit models and recognize enrollment practices that improve representative participation.
Operational Constraints and Real-World Pressures
Contract research organizations and study sites often face pressure to meet enrollment timelines and budgets, which can deprioritize balanced recruitment. Framing enrollment equity as an early feasibility and quality risk, rather than a late-stage aspiration, allows teams to intervene proactively, reducing downstream delays, screen failures, and protocol deviations.
Limitations
This qualitative synthesis is limited by heterogeneity of study designs and outcomes and by reliance on English-language publications. A formal risk-of-bias assessment was not performed; however, potential sources of selection and attrition bias were considered when interpreting enrollment patterns. Several trials enrolled small numbers of women, limiting sex-specific inference.{1,4}
Conclusion
Women remain underrepresented in CAD clinical trials despite established cardiovascular risk and regulatory emphasis on representative enrollment.{1–4} Patient-centered interventions alone are insufficient to correct these disparities.
Clinical research professionals play a central role in advancing sex-balanced enrollment through intentional feasibility assessment, proactive monitoring, and operational flexibility. Addressing enrollment equity during trial planning strengthens data validity, improves efficiency, and advances equitable cardiovascular research.
References
- Tsang W, Alter D, et al. 2012. The impact of cardiovascular disease prevalence on women’s enrollment in landmark randomized cardiovascular trials: a systematic review. J Gen Intern Med 27(1):93–8.
- Matthews S, Cook S, et al. 2024. Factors affecting women’s participation in cardiovascular research: a scoping review. Eur J Cardiovasc Nurs 23:107–14.
- Harris DJ, Douglas PS. 2000. Enrollment of women in cardiovascular clinical trials funded by the National Heart, Lung, and Blood Institute. N Engl J Med 343(7):475–80.
- Rivera F, Magalong J, et al. 2025. Participation of women in cardiovascular trials from 2017 to 2023: a systematic review. JAMA Netw Open 8(8):e29104.
- Bernal-Jiménez A, Calle G, et al. 2024. Effectiveness of an interactive mHealth app in improving lifestyle after a coronary event: a randomized controlled trial. JMIR Mhealth Uhealth 12.
- Li Y, Li C, et al. 2025. Tai Chi as a mind–body exercise modulates endothelial function in coronary artery disease: a randomized clinical trial. Complement Ther Med 92.
- Mury P, Dagher O, et al. 2025. Quercetin reduces vascular senescence and inflammation in symptomatic coronary artery disease patients. Aging Cell 24.
- Stewart S, Patel S, et al. 2024. Vulnerability to environmental and climatic health provocations among women and men hospitalized with chronic heart disease: insights from the RESILIENCE trial cohort. Eur J Cardiovasc Nurs 23:278–86.
- Yildiz F, Kasikci M. 2020. Impact of training based on Orem’s theory on self-care agency and quality of life in patients with coronary artery disease. J Nurs Res 28(6).
- Sterne JAC, Savović J, Page MJ, et al. 2019. RoB 2: a revised tool for assessing risk of bias in randomized trials. BMJ 366:l4898.
Patricia Fitzgerald, MS, is a PhD student in the Clinical Research program at the University of Jamestown in North Dakota and a Clinical Research Associate Assistant Manager with Abbott.
