Study Shows Progress in Women’s Inclusion in Clinical Trials

Women are now substantially represented in clinical trials for FDA-approved drugs, according to a new study led by Sophie Zaaijer, PhD. Yet gaps persist, signaling there’s more to be done in making medicine truly equitable.

There’s good news to report when it comes to women’s health. A new study provides encouraging evidence that most clinical trials have substantial female representation relative to disease burden. The study also shows an increase in therapeutic investment for diseases affecting women.

“These results show promise — the field has moved beyond widespread exclusion,” says Sophie Zaaijer, PhD, who led the study as a research specialist in the Division of Hematology and Oncology at the UC Irvine School of Medicine. “At the same time, the work also signals a shift in thinking.”

As women are increasingly included in trials, Zaaijer and her colleagues are now challenging the field with a deeper question: Are we truly studying women — or simply counting them?

The Good News

Zaaijer worked with Simon C. Groen, an assistant professor of evolutionary systems biology at UC Riverside, to analyze data from 2015–2023 for 195 FDA-approved drugs across 98 disease indications. Their findings, published in Nature Communications, show that 67% of pivotal trials met or exceeded expected female participation relative to disease burden. They also found a 5.5-fold higher FDA approval rate for therapies addressing female-specific indications.

“We saw several areas where clinical trial representation is working well,” says Zaaijer. For example, in oncology, approximately 83% of trials aligned with disease burden, and in neurology, representation often exceeded expected levels. The study also revealed balanced enrollment relative to disease burden for conditions with clear diagnostics and objective endpoints.

Zaaijer points (in the “extensive discussion” section of the paper) to key factors that allow for this progress in cancer-focused clinical trials:

• Precise diagnostics and biomarkers that define patient populations;
• Objective clinical endpoints (such as survival or tumor response); and
• Older patient populations, reducing barriers related to reproductive safety.

“These areas suggest that when diseases are well-characterized and measurable,” she says, “representation improves.”

Where Gaps Persist

Despite overall progress, disparities remain concentrated in specific areas. The study found that approximately 73% of cardiovascular disease trials and 68% of autoimmune and inflammatory disease trials under-enroll women.

“Many of the methods and benchmarks used in clinical research were developed around male physiology, which can unintentionally disadvantage women throughout the clinical trial process,” says Zaaijer.

Most clinical trials still rely on a single protocol and set of enrollment criteria for both men and women. While trial results often report the proportion of women enrolled — and sometimes analyze efficacy by sex — adverse events are typically reported in aggregate.

“As a result, we may be missing female-specific biological variables that influence diagnosis, eligibility for clinical trials, treatment response and toxicity,” says Zaaijer, “which could explain the under-enrollment in certain disease areas.”

Tracking how people respond to a drug can also be impacted, as clinical trials continue to rely on static, single-timepoint measurements rather than tracking physiology over time, potentially overlooking important biological variation in women.

According to Zaaijer, key dimensions of female biology — including the dynamic hormonal state of women during pregnancy, menopause and other life-stage transitions — are not consistently incorporated into trial design or data reporting. So how do we find out if these are important if they’re not measured?

Inclusion Is Only the First Step

“Counting women in clinical trials is important, but we also need research methods and reporting standards designed to understand how women experience disease, treatment response and toxicity,” explains Zaaijer. “By measuring what matters, we can uncover new biological insights and improve care for millions of patients.”

Zaaijer further explores these questions with School of Medicine colleagues Arash Rezazadeh Kalebasty, MD, and Shera Feinstein, MD, alongside David Benjamin, MD, of Hoag — all leaders in genitourinary (GU) oncology. They wrote a Nature Reviews Urology commentary together titled, “Why Counting Women Is Not Enough: From Inclusion to Equity in Oncology Trials.”

“A number of studies have shown that women receiving chemotherapy, immunotherapy or targeted therapies experience significantly higher rates of severe adverse events than men,” says Benjamin, a medical oncologist who was the commentary’s lead author. “In one large analysis, women had a 34% higher risk of severe treatment-related toxicities.”

Researchers are still trying to figure out why women experience higher rates of severe adverse effects than men.

“Female physiology remains understudied and underreported in oncology research,” says Benjamin.

Bladder cancer is three to four times less common in women than in men, which inherently limits female representation in clinical trials. However, Benjamin stresses that “reporting and disseminating sex-specific adverse event data can provide clinicians with valuable guidance on what to anticipate, monitor and manage in female patients.”

Rezazadeh, also a medical oncologist, adds that there is a need for clinicians to publish evidence that guides the management of treatment-related toxicities. “Ultimately, a more sex-specific approach to understanding and managing cancer care may improve outcomes for patients,” he says. “It could also potentially reduce the burden on the healthcare system.”

Radiation oncology provides a clear example of this gap. “Most women experience some degree of sexual dysfunction following pelvic cancer treatment, yet these effects are rarely assessed in a systematic way,” says Feinstein, a radiation oncologist. “Without consistent measurement and reporting, we miss opportunities to better understand and address complications that can significantly impact quality of life.”

The team is excited to work on clinical trial frameworks to better address this in the future.

A New Era in Women’s Health

At the Health Equity & Research Summit (HERS), Zaaijer continued the discussion as moderator of a panel talking about “Why Counting Women Is Not Enough.” The panel brought together leaders from clinical development, digital health, molecular diagnostics and patient-centered research to explore what comes next after improving representation in clinical trials.

Panelists emphasized that future progress will require expanding both how clinical trials are designed and what they measure. Discussions ranged from challenges associated with one-size-fits-all trial protocols to opportunities for incorporating additional biological variables, longitudinal data, and digital health technologies.

The panel also explored longer-term priorities, including building large-scale women’s health datasets, integrating more nuanced biological data into healthcare systems, and developing new frameworks for data collection and collaboration.

“The discussion was incredibly insightful, getting to practical steps to the needs beyond improving representation in clinical trials,” said Zaaijer. “I hope this marks a turning point, opening the door to a new generation of research questions about how clinical studies can better reflect human biology and make medicine more equitable.”

— Shani Murray