Unveiling the truth: A journey into women’s representation in clinical trials

When we explore the history of our clinical trial world, it’s no secret, the voices and experiences of those assigned as women at birth have been missing for far too long.  

But what sparked this in the first place? Let’s journey back in time together.  

Back in the day  

In the 1970s, decision-makers of clinical trials believed women’s hormonal cycles would twist, turn, and skew data. Men were seen as the ‘normal’ study population, while women were considered more biologically complex. Even more interestingly, people held an assumption that there were no significant differences in how men and women responded to treatment. It’s hard to believe these misguided thoughts existed, given how far our industry has advanced. ^1,2

What’s more, even before the 1970s, women were often sidelined in medical research. And as some of us remember, the situation worsened after the thalidomide tragedy, sparking fears, leading to much stricter rules and regulations.¹

Then 1977 happened.  

This is when the FDA took a drastic step to ban women of reproductive potential from taking part in early-phase clinical trials. Originally intended as a protective measure, the policy was overly broad, also barring single women and those on contraception. Effectively shutting women out from crucial medical advancements.¹

An incomplete picture

Of course, there are huge consequences to this which we all care about.

Excluding women from clinical trials limits understanding of how conditions manifest and how treatments work differently. And as we know, knowledge is power. So when we don’t have the insight and info we need, suboptimal treatment efficacy and undesirable adverse events become the stark reality.  

But let’s dive deeper.  

The missed opportunities

Not representing women in the way they deserve has left us with big gaps.  

Take cardiovascular disease, for example. The leading cause of death for women in the US but with different symptoms, risk factors, and outcomes in women compared to men. Yet only one-third of all cardiovascular clinical trial participants are women. And only 31% of these trials report data by sex. And, as we all live and breathe, data is how we progress.³

What else?  

As we know, women and men process drugs differently due to differences in body composition, hormonal cycles and enzyme activity. For example, women generally have a higher percentage of body fat and less body water, which can change how drugs are distributed and eliminated. When women are left out of clinical trials, we miss out on crucial insights into these differences. This can lead to dosing recommendations and safety profiles that aren’t tailored for women, risking overmedication or undermedication. Increasing the likelihood of adverse events and efficacy issues.⁴

But the saga continues.  

We know women experience changes throughout life, such as with the menstrual cycle, pregnancy, and menopause. These hormonal fluctuations can influence how diseases manifest and how treatments work. For instance, the efficacy and side effects of certain medications can vary depending on the phase of the menstrual cycle.⁴

To get even more specific, we know hormonal changes throughout a woman’s life are linked to an increased risk of conditions like depression. And as we mentioned, women metabolise drugs in a different way to men, so why is it fewer than 45% of preliminary studies in depression and anxiety use female lab animals?⁵

Hypertension tells a similar tale too. We know the same approach to managing the condition is recommended in both men and women. But given how, historically, we’ve overlooked biological differences, this can’t be the most effective solution.⁵

So what can we do to address women’s representation?  

In 1988 the FDA shone a spotlight on the importance of examining data for gender-based differences in safety and efficacy within their guidelines. And by 1993, they lifted the ban on women participating in clinical research. A crucial step forward. Following this, the National Institute of Health (NIH) outreach ‘Notebook’ was created to help support recruitment of women, advancing our strategy for women’s health.⁶

But even though women can now participate in most clinical trials they’re eligible for, representation still varies.⁶

How can we continue to make progress and improve representation?  

It’s about making our communications clear, empathetic and personal. It’s about making everyone feel at home and included. And speaking of inclusion, we have to include everyone, including those who have been marginalised for far too long, such as the non-binary and transgender community. In fact, we’ll be diving into this further in our next blog, so stay tuned!

Ultimately, if we take these steps, we can make women feel like true partners and at the very heart of clinical trial design. As they always should have been.  

References

1. AAMC. Why we know so little about women’s health. Available here. Accessed: June 2024.
2. wellandgood. Women were left out of clinical trials until the ‘90s – this is how it’s impacted our health. Available here. Accessed: June 2024.
3. The Guardian. The medical research gender gap: how excluding women from clinical trials is hurting our health. Available here. Accessed: June 2024.
4. DigitalCommons. A history of the representation of women in clinical trial: Implications for modern health care. Available here. Accessed: June 2024.
5. Mastroianni AC, et al. Health Consequences of Exclusion or Underrepresentation of Women in Clinical Studies. In Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies. Vol. 2; National Academies Press, 1999. DOI: 10.17226/2343.
6. NIH. NIH Inclusion outreach toolkit: How to engage, recruit, and retain women in clinical research. Available here. Accessed: June 2024.

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