In 2013, the FDA took the uncommon step of requiring manufacturers of certain zolpidem-based insomnia drugs like Ambien to reduce the recommended starting doses for women. The decision came more than 20 years after the drug hit the market when fresh research found that female users cleared the drug more slowly than men, potentially putting them at higher risk for impaired driving the morning after they took it.
“One reason for the roughly two-decade delay in taking this measure was that crash reports were too confounded — by uncertainty around dose, timing and co-ingestants — to isolate risks attributable to the drug,” the authors of a study published in Nature Communications wrote.
The late reaction by the FDA showcased why it’s critical to ensure that women participate in clinical trials, and that trials are designed to pick up on impactful sex-specific differences.
But after years of exclusion from many early-stage drug trials, women are still making up ground when it comes to playing a role in R&D.
Progress and setbacks
The thalidomide tragedy helped drive restrictions on women’s participation in drug trials. The drug, used to treat morning sickness, caused severe birth defects, contributing to a 1977 FDA recommendation to exclude women of childbearing potential from phase 1 and early phase 2 trials.
The federal government began to reverse course a decade later, starting with a 1986 NIH-funded study that encouraged researchers to bring women back.
Pharma and biotech drug R&D is also helping to turn the tide.
Among drugs analyzed between 2015 and 2023, treatments for female-predominant conditions received about 1.5 times as many approvals as those for male-predominant conditions, according to the Nature Communications research.
Female enrollment matched or exceeded women’s share of the disease population in about two-thirds of the trial cohorts analyzed, the Nature research authors wrote.
But not all trends have been moving in the right direction.
The researchers detected no significant improvement during the period studied and participation in different therapeutic areas was inconsistent. For example, women made up their fair share, or more, based on disease prevalence in 67% of all the trials researchers reviewed. But women were underrepresented in 73% of cardiovascular and 68% of autoimmune/inflammatory trials.
Participation also varied by disease within these areas. In rheumatoid arthritis, for example, where women make up 71% of cases, there was high female participation — between 79% and 82%. But in plaque psoriasis, where women make up around half of the patient population, women only accounted for about 30% of participants on average.
Attracting women into clinical research
While the data shows progress, the enrollment process is too often reactive instead of proactive, according to Katrina Rice, chief delivery officer of biometric services at eClinical Solutions, a clinical data software and biometrics services provider. Women often seek out studies when they are looking for treatment options, she said, rather than pharma companies effectively recruiting them for trials.
A major barrier is how healthcare is delivered, Rice said. While many women get care in community-based practices, physicians in those clinics face challenges getting patients into trials because they lack the needed trial infrastructure and information.
Technology can help bridge this gap, Rice said. Many community practices are now digitally linked to larger hospital networks through electronic health records, offering an opportunity to deliver personalized recommendations to patients about their care and potentially about available trials. AI tools can also better tailor recommendations to individual patients, she added.
Increasing trial visibility also remains critical. When people see that others like themselves are in a trial, it can change how they feel about participating, Rice said. Trial sponsors that share participation data and patient testimonials can make clinical research feel more accessible.
“I think people like to hear from people,” she said.
But improving health outcomes will require more than just bringing in more women. Trials also need more diverse groups of women, Rice noted.
And study design is another important consideration. Trial design should be structured to capture efficacy or safety signals, including sex differences in metabolism, hormones, immune response, pharmacokinetics and how disease progression impacts treatment response and side effects, Rice said. This will require an intentional approach by pharma.
“I think the needle is moving, but there is always more work that we can do,” Rice said.
