The under-representation of women in cardiovascular clinical trials: State-of-the-art review and ethical considerations

Abstract

• The Status quo: The under recruitment of women to clinical trials has an impact on the generalizability of trial data, limiting the detection of sex-based interactions and appropriate sex specific recommendations. • The clinical implications: Addressing under-recruitment of women is an important step toward closing the data gap for women with cardiovascular disease, with the potential to improve outcomes and achieve equity of care for women with cardiovascular disease. • The power of change to address disparity and data gaps: Strategies to address representation of women as investigators and authors in these trials are needed, as higher inclusion of women has been shown to increase recruitment of women as participants. • The timing of this article: the Diversity Action Plans for clinical trials announced by the United States (US) Food and Drug Administration (FDA) in 2024, with requested public comments, the inclusion of MINOCA recommendations in the ESC 2024 guidelines, 2021 US Chest Pain guidelines, and the 2023 US guidelines for the Management of Chronic Coronary Disease, all demonstrate the need for increased awareness of the under-representation of women, and solutions for change. This review describes and evaluates the representation of women in cardiovascular randomized controlled trials (RCT), it reports significant under-representation of women in clinical trials both as participants and researchers and discusses the ethical implications of under-representation. The under-representation of women as participants in cardiovascular RCTs is evident in trials investigating cardiovascular drugs, acute coronary syndrome, heart failure and interventional procedures and devices. Under-representation of women is also evident in the authorship of cardiovascular clinical trials and in trial leadership roles, and under-representation of women as trial investigators is independently associated with under- recruitment of women as trial participants. A notable lack of RCTs investigating conditions that disproportionately affect women is also evident, this triad of underrepresentation for women as participants, and investigators, and the lack of RCTs into conditions predominantly experienced by women, all contribute to the gender gap in cardiovascular outcomes. Better representation of women in clinical trials, in trial leadership and authorship is a key factor to address to equity, distributive justice and improve outcomes for women with cardiovascular disease.

Topics & Concepts