It is important that scientific studies represent the diversity of the population, and we will see more equity in clinical trials and new technologies to help increase female participation with minimal disruption of daily life, according to experts in this guest article by Women in Nutraceuticals.
Introduction
Women spend 25% more of their lives in poor health versus men, averaging nine years. Despite women comprising half the population, less than half of research funding goes toward understanding female health. More than half of the health gap for women occurs during their working years; investments addressing the women’s health gap could potentially boost the global economy by $1 trillion annually by 2040.[1,2]
Women are the foundation of healthy families and of prosperous economies, as they make 80% of purchasing decisions and invest their salaries in their families. However, women are underrepresented in clinical trials and conditions affecting them are researched far less than those impacting men,[3,4], which is further exacerbated by underrepresentation of women as principal investigators and researchers. The lack of funds used for women’s health is costing the global economy; thus taking greater stock in women’s health serves as a solid investment for societies and economies worldwide. [5]
Shattering the Status Quo
The lack of inclusion of women in clinical trials is one of the reasons for the aforementioned health gap, which has led to a data gap and inadequate understanding of how drugs affect women. [6,7] This lack of knowledge can escalate healthcare costs due to misdiagnoses, ineffective treatments, and the need for additional medical interventions to manage side effects or complications that otherwise could have been avoided with more gender-specific research.
“Due to a historical exclusion of women from clinical trials, today we have a major gap in our understanding of how medicines influence women differently from men,” explains Cynthia Suarez-Rizzo, PhD, New Product Development expert at Finzelberg.
According to Suarez, women experience adverse events from approved medications 52% more often than men and, rather alarmingly, suffer from serious or fatal events 36% more frequently than men. This underscores the importance of understanding differences between sexes, as she states, “it is important that we understand that women are not just smaller men, but they also have a very different physiology, so we need to study them differently.”
Suarez-Rizzo adds that hormonal differences cause variability in aging and mental health, as well as in the function of the microbiome. Moreover, with some health concerns like cardiovascular disease, physical performance, cancer, and sexual issues, the differences in physiology play a crucial role in their prevention, treatment and responses to treatment, and disease progression.
The lack of a clear understanding of differences between males and females can result in treatments that are less effective at best and harmful at worst. “By increasing the number of studies as well as the participation of more women in clinical trials for supplements and medicine, these issues could be solved way faster than we think,” she said. And part of the solution could lie in AI-based research tools that are tailored to female biology, which can help augment clinical trials by creating more nuanced models and considering a wider range of biological and physiological variables related to sex and gender.
Why are Women Still Underrepresented in Clinical Trials?
Despite efforts to include more women in clinical trials, their representation remains low. In fact, a recent meta-analysis showed less than 50% of participants were women in 300 trials evaluated,4 and that women comprise only 29-34% of participants in phase I trials. [8] While scientists have concerns over female participation in trials, women themselves also have several concerns limiting their own participation.
Pregnancy is a critical safety concern among investigators and study sponsors, according to Suarez-Rizzo, who also cites the financial and legal risks that arise if a woman becomes pregnant during a clinical trial.
“Age-related biological differences and women’s hormonal fluctuations can introduce variability into clinical trial data, adding complexity and potentially increasing costs,” Suarez-Rizzo explains.
While including both sexes in clinical trials might initially seem to increase costs, due to the need for larger participant groups to accommodate variability, the broader perspective suggests this inclusion is crucial for developing more effective and safer treatments. Ensuring more precise and effective treatments will lead to improved healthcare outcomes for women and reduced long-term healthcare costs.
Monica Olivares Martín, PhD, R&D Director Women and Infant Health at Kerry, highlighted some of the reasons for the underrepresentation of women in clinical research, including perceived harm. [9] Harrison et al. analyzed survey data from 97 women who were invited to participate in at least one of four heart failure studies but declined. [10] The study found four major deterrents to patients' participation: (1) lack of interest, (2) lack of time, (3) poor health, and (4) travel burden.[5]
“Females, especially those who are underrepresented minorities, often have decreased trust in the healthcare system due to poor interaction and communication with healthcare providers,” according to Olivares Martín.
To that end, she insists that improved communication and building a trusting relationship with women should be a priority for investigators, including open discussions between the research site staff and patient when discussing trial enrollment and properly disclosing risks and benefits of trial participation. Additionally, support with transport, childcare, and flexible hours for clinical visits would help to increase the participation of women.
Influence of Gender Disparity Among Investigators
Another important factor influencing the participation of women in clinical trials are gender disparities among principal investigators of clinical trials, which can affect trial enrollment. According to Bharat Rawlley et al., gender makeup of principal investigators can have a significant influence on the area of investigation of a clinical trial as well as its design, conduct, and interpretation of results. [11]
Data from Stanford professor Celina Yong et al. showed studies involving women investigators enroll 7% more women patients than studies without women investigators. [12] Meanwhile, 45% of studies led by women enrolled women, only 38% of studies led by men enrolled women.7
Although there has been a notable increase in the proportion of women principal investigators over time, the overall representation of women investigators remains relatively low at 14-22%, depending on the subgroup analyzed. [7,13] This indicates the need to address underrepresentation of women leading clinical trials — not just hurdles keeping women from participating — in order to produce better data and offer better treatments.
Conclusion
Addressing the above-mentioned issues will not only improve healthcare outcomes and quality of life for women, but it will also reduce long-term healthcare costs, according to The Global Alliance for Women’s Health, which firmly believes that investing in women’s health is in the best interest for societies and economies. [3]
Closing the data gap is imperative to ensure development of safe and effective treatments, leading to more precise and effective healthcare for women. Regulatory enforcement, new research approaches and tools, inclusive recruitment practices, financing of research in women’s health, and involvement of female investigators all are essential for the inclusion of women in clinical trials.
In March 2024, US President Joe Biden signed an executive order and the National Institutes of Health pledged $200 million to better understand women’s health issues; to improve the recruitment, enrollment, and retention of women in clinical trials; and to identify and erase gender gaps in research. [14]
This is an important step that will hopefully lead to more studies on women led by women. Olivares Martín confirms this, noting we will see more equity in clinical trials in the future, as well as new technologies to help increase female participation with minimal disruption of daily life. “A high-quality study has to represent the diversity of the population and researchers need to drive this change, including in their clinical programs strategies to facilitate the enrollment of women,” she said.
Authors:
Devon Gholam, PhD, is the Vice President of Science and Innovation at Step Change Innovations and Co-Chair of the Science Content Subcommittee for Women in Nutraceuticals
Julia Wiebe, PhD, is the Managing Director red otc development GmbH and founding Board Director of Women in Nutraceuticals
Contributing Experts:
Cynthia Suarez-Rizzo, PhD, is an Expert for New Product Development at Finzelberg, a German supplier of science-backed branded ingredients and botanical APIs
Monica Olivares Martín, PhD, is the Research and Development Director for Women and Infant Health at Kerry and a member of the Women in Nutraceuticals Science Committee.
References
[1] World Economic Forum. 2024. Why the women’s health gap exists—and how to close it—according to experts at Davos. Available online: https://www.weforum.org/agenda/2024/01/women-health-davos-2024/.
[2] McKinsey Health Institute. 2024. Closing the women’s health gap: A $1 trillion opportunity to improve lives and economies. Available online: https://www.mckinsey.com/mhi/our-insights/closing-the-womens-health-gap-a-1-trillion-dollar-opportunity-to-improve-lives-and-economies
[3] Yakerson, A. 2019. Women in clinical trials: a review of policy development and health equity in the Canadian context. Int. J. Equity Health 18: 56.
[4] Daitch, V., et al. 2022. Underrepresentation of women in randomized controlled trials: a systematic review and meta-analysis. Trials 23: 1038.
[5] World Economic Forum. 2024. The Global Alliance for Women’s Health. Available Online: https://initiatives.weforum.org/global-alliance-for-womens-health/home
[6] Ravindran, T.K.S., et al. 2020. Making pharmaceutical research and regulation work for women. BMJ 371: m3808.
[7] Schiebinger, L. 2003. Women’s health and clinical trials. J. Clin. Invest. 112 (7): 937-977.
[8] Fultinavičiūtė, U. 2022. Sex and science: underrepresentation of women in early-stage clinical trials. Clinical Trials Arena. Available online: https://www.clinicaltrialsarena.com/features/underrepresentation-women-early-stage-clinical-trials/.
[9] Peterson, E.D., et al. 2004. Willingness to participate in clinical trials. Am. J. Geriatr. Cardiol. 13 (1): 11-15.
[10] Harrison, J.M., et al. 2016. Refusal to participate in heart failure studies: do age and gender matter? J. Clin. Nurs. 25 (7-8): 983-991.
[11] Rawlley, B., et al. 2023. Investigation on Gender Differences in Leadership of Stroke-Related Clnical Trials. Stroke 54 (2): 295-303.
[12] Yong, C.M., et al. 2022. Sex of Principal Investigators and Patients in Cardiovascular Clinical Trials. JACC 79 (9 suppl A): 1470.
[13] Whitelaw, S., et al. 2020. Characteristics of heart failure trials associated with under-representation of women as lead authors. J. Am. Coll. Cardiol. 76 (17): 1919-1930.
[14] National Institutes of Health. 2024. President Biden Issues Executive Order on Advancing Women’s Health Research and Innovation. Office of Research on Women’s Health. Available online: https://orwh.od.nih.gov/in-the-spotlight/all-articles/president-biden-issues-executive-order-on-advancing-womens-health-research-and-innovation.
