With treatment responses differing among men and women, it is critical to consider sex differences in clinical studies

By Kristen Snipes, Director, Clinical Operations, Health Decisions 

Is being female a pre-existing condition? In the world of clinical research that was once the prevailing notion. In the past, researchers excluded women from trials because they believed their fluctuating hormones might cause them to respond differently to treatments, complicating the trial design and study results. Since control is the goal in any clinical environment, an all-male cohort of patients made sense.  

For decades, drugs were approved without being tested on women or factoring in whether women would have different reactions or require different dosages than men. Well-meaning policies, such as this 1977 U.S. Food and Drug Administration (FDA) policy, previously recommended women of childbearing potential be excluded from Phase I and early Phase II drug trials due to fears about the effects of experimental drugs on unborn children. This was true even for drugs specifically targeting women. In one famous study of the interaction between alcohol and flibanserin – also known as ‘female Viagra’ – 23 of the 25 study participants were male

 This male-dominated research culture has resulted in a shortage of data about the long-term effects of medicines on women, putting women at risk and making manufacturers vulnerable to the consequences of unexpected outcomes. For instance, the U.S. Government Accountability Office found that 80 percent of drugs pulled from the market due to unacceptable health risks between 1997 and 2001 were discovered to be more harmful to women than to men.  

Attitudes around involving women in clinical trials have evolved significantly in the past 25 years as research emerged proving the importance of studying biologic, physical and behavioral differences between genders. However, despite new expectations from regulators pushing for women to be involved in studies, parity has yet to be achieved.  

One 2018 study published in the Journal of the American College of Cardiology (JACC) found that in trials supporting 36 cardiovascular approvals, just 34 percent of trial participants were women, despite the fact that cardiovascular disease is the leading cause of death among women.  

The same study found that while men and women pass screenings for trials at roughly the same rate, fewer women go through screening. This suggests women may be less aware of opportunities, more skeptical of the benefits of participation, or they may face additional barriers, including transportation and child or elder care, that prevent their involvement. 

Even when women are adequately represented in clinical research, analysis of data based on gender is uncommon, which means the industry is missing opportunities to identify gender differences in response to medical treatments, and to uncover new insights into the benefits and potential risks of treatments based on gender.  

As an industry we need to continue promoting the benefits of involving women in clinical research, both for patients and sponsors, and adapting the trial environment to accommodate their needs.  

We have seen a number of advocates for women in research emerge in the public and private sectors in recent years, including the NIH’s Office of Research on Women’s Health and the Society for Women’s Health Research. Organizations, regulatory agencies and study sponsors are amplifying the conversation around the importance of involving women in clinical trials and helping the industry understand how best to recruit and retain female studies participants.  

At Health Decisions, we’re actively participating in this discussion and sharing our expertise from more than 29 years of experience in women’s health research. Many of the challenges for recruiting women can easily be addressed through more thoughtfully planned recruiting communication strategies and more adaptive trial settings, including: 

  • Posting recruiting messages in pediatrician’s offices, senior centers, grocery stores, salons, and other places with largely female clientele 
  • Partnering with female-driven patient advocacy groups to communicate about these opportunities, and to have conversations about the safety, value, and expectations of trial participation 
  • Extending trial site hours into evenings and weekends, and offering child care, travel stipends, and free parking to ease the burden of site visits 
  • Leveraging telemedicine where appropriate to reduce the number of site visits 
  • Using social media platforms to promote trial participation and what it involves, and to share real-life stories of women who have participated in trials to make an emotional connection with readers 

“If sponsors want to reduce the risk of unexpected real-world treatment outcomes, they need to adapt their recruiting methods to attract more female subject and set-up trial environments that accommodate women’s needs.” 

Good for research 

Efforts to involve women in research are critical as these initiatives can help sponsors understand gender differences in response to treatment and allow them to uncover potential adverse events that could impact a treatment’s market status and labeling claims. If sponsors want to reduce the risk of unexpected real-world treatment outcomes, they need to adapt their recruiting methods to attract more female subjects and set-up trial environments that accommodate women’s needs. Doing so will ensure the data needed to prove a treatment is safe and effective across gender lines is gathered. 

Learn more about the importance of including women in clinical trials, read: Addressing the New Imperative to Include Females in Clinical Trials.