Insights from Aman Khera: Promoting the Inclusion of Women in Clinical Research

Author: Aman Khera, MBA, FTOPRA, FRAPS – VP, Regulatory Science, Strategy and Innovation

Three years ago, I contemplated the impact of inequality in clinical research for women¹. I emphasized the persistent underrepresentation of women in clinical trials, a gap that can have serious consequences. With biological differences and incorrect dosages insufficiently explored during drug development, the lack of representation can lead to adverse side effects for women. Women experience these adverse drug reactions nearly twice as often as men, resulting in frequent cases of overmedication. My stance was clear: efforts must focus on increasing women’s participation in trials, particularly during early phase research.

As we mark Women’s History Month, I find myself reflecting once more. There have been encouraging shifts in our industry with a new era emerging of Regulatory Agencies, expecting sponsor companies to communicate their efforts to make clinical trials more inclusive. Despite remarkable scientific advancements, why does the health of at least half the global population, women, continue to be overlooked? Why are women’s voices routinely ignored?

The statistics show that women, on average, live longer than men. Yet, they grapple with more chronic illnesses and are frequently misdiagnosed. When presenting symptoms, they are often taken less seriously. Gender bias in medicine perpetuates a troubling pattern: women patients are denied adequate pain relief across various health conditions. But it’s not just about pain; there’s a credibility gap too. Women’s experiences and concerns about their bodies are often dismissed.

We must engage in open dialogue, address these disparities, and empower women to make informed decisions about their health. We must make efforts to bridge the gaps and ensure that women’s well-being receives the attention it deserves.

Inequity in clinical research has reinforced gender bias. For example, throughout history, many scientists have believed that males were the best test subjects because they do not have menstrual cycles and cannot become pregnant. As a result, a vast amount of research has been highly limited by only involving male participants. However, important biological differences between the sexes can influence how diseases, drugs, and further therapies affect people, meaning many studies from the past could be flawed due to their gender bias. The overall consequence of gender bias in healthcare is that women receive worse care than they should, which increases their health inequity^2,3.

The lack of inclusivity in clinical research has led to gaps in knowledge, which means physicians know less about women’s and trans health than male health. Additionally, when physicians do not take women’s symptoms seriously, these delayed diagnoses can keep women from receiving a correct diagnosis.

For us to play our part in having an equitable lens for women, we must continue to make solid strides in clinical research for the unheard voices. Gender equality in clinical research is crucial for ensuring safe and effective treatments for everyone. And we must continue working toward a more equitable future, even with an increasing number of women leading studies⁴.

At Worldwide, we serve to implement effective strategies to recruit and retain women in clinical trials while respecting cultural intersections.

Worldwide’s Health Equity strategies have evolved. We were thinking about this long before the US FDA considered Diversity Action Plans. Now, we are thrilled to work with sponsor companies eager to make a positive impact on Health Equity.

To ensure the inclusion of women as clinical trial participants, we work closely and encourage sponsor companies designing and undertaking clinical trials to consider the following steps:

Consultation with Regulatory Authorities:

• Engage with regulatory agencies during trial planning and design.
• Seek guidance on best practices for including women and analyzing sex differences.

Study Design Considerations:

• Purposeful Inclusion: Companies should intentionally include women in clinical trials from the outset. This inclusion involves considering sex-specific factors during study design, such as hormonal variations, metabolism, and potential side effects.
• Sample Size: Ensure that the sample size includes an adequate representation of women. Current guidelines recommend proportional representation based on the prevalence of specific health conditions⁵.
• Sex-Related Differences: Companies must recognize that women may respond differently to therapeutic products due to biological variations. Design studies to identify these sex-related differences.

Informed Consent and Pregnancy Prevention:

• Informed Consent: Clearly communicate the study’s purpose, risks, and benefits to potential participants. Address any concerns related to participation.
• Pregnancy Prevention: Implement effective strategies to prevent inadvertent pregnancies during clinical trials, including providing contraceptive options and educating participants about their use.

Risk Management and Pharmacovigilance

• Develop robust risk management plans that account for sex-specific adverse events.
• Monitor safety data and address any emerging risks promptly.
• Consider the impact of therapeutic products on pregnant and breastfeeding women. Include them in post-market studies to gather real-world evidence.

Recruitment and Retention Strategies

To optimize recruitment, consider the following:

• Community Engagement: Leverage relationships with community providers, clinics, and local organizations. Host informational sessions or workshops to raise awareness about the disease being treated and a potential trial.
• Patient Advocacy Groups: Collaborate with patient advocacy organizations focused on women’s health. They can help spread the word and encourage participation.
• Tailored Messaging: Propose using a mix of approaches, such as social media, community outreach, and healthcare provider referrals. Develop targeted recruitment materials that resonate with women. Highlight the potential impact of their participation on women’s health.

To consider retention strategies:

• Participant-Centric Approach: Prioritize participant safety, well-being, and trust. Regularly check in with participants and address any concerns promptly.
• Flexible Scheduling: Accommodate women’s schedules by offering flexible appointment times. Consider evenings or weekends to accommodate work and family, as well as caregiving commitments.
• Transportation Assistance: Provide transportation options or reimburse travel expenses swiftly. Lack of transportation can be a barrier to retention.
• Cultural Competence: Train study staff to be culturally sensitive. Understand and respect diverse backgrounds and beliefs.
• Regular Communication: Maintain open lines of communication. Send visit reminders, share study updates, and express appreciation for participants’ contributions.

Finally, evaluate and adapt:

• Monitor Progress: Regularly assess recruitment and retention rates. Identify any drop-offs and address them promptly.
• Feedback Loop: Collect feedback from participants. Understand their experiences and use insights to refine strategies.

Education and Awareness:

• Raise awareness among researchers, investigators, and study teams about the importance of gender equity in clinical trials.
• Promote training on sex-specific considerations and encourage a gender-sensitive approach throughout the trial process.

Above all, to listen to clinical trial participants and allow them opportunities to give feedback, we must place the patient-first lens front. Consider truly involving representatives of the patient population by creating advisory boards with diverse members, including women who have participated in clinical trials. Their insights can guide recruitment and retention strategies.

Another valuable idea is to give peer support and encourage participants to connect with each other. Peer support groups can foster a sense of community and motivation to stay engaged⁶.

Gender equality in clinical research is crucial for ensuring safe and effective treatments for everyone. And we must continue working toward a more equitable future.

Worldwide is proud to play our part in driving health equity in clinical research. We commit to making a positive difference.

We are these women. They are our friends, grandmothers, mothers, sisters, and daughters.

References

1. Let’s Talk About Gender Equality in Clinical Research
2. “Twenty Years and Still Counting: Including Women as Participants and Studying Sex and Gender in Biomedical Research”
3. Making pharmaceutical research and regulation work for women BMJ 2020; 371 doi (Published 27 October 2020),  BMJ 2020;371:m3808
4. “Why More Women Should Lead Clinical Trials”
5. Women in Clinical Trials: Patients
6. Strategies for Enhancing the Representation of Women in Clinical Trials: An Evidence Map Goldstein, K.M., Kung, L.C.Y., Dailey, S.A. et al. Syst Rev 13, 2 (2024). https://doi.org/10.1186/s13643-023-02408-w