By Deborah Borfitz 

March 15, 2023 | Two different perspectives on the participation of women in clinical trials arise when looking at the situation locally and internationally. At the ground level in the U.S., at least on protocols that don’t exclude them, women often outnumber men by a wide margin even if all socioeconomic subgroups aren’t represented. On the other hand, females account for only about 31% of study participants across all 450,000 ongoing global trials, and their enrollment in some of the most highly funded areas of research—including Alzheimer’s disease, cardiovascular disease, and cancer—isn’t keeping pace with real-world disease prevalence rates. 

These are among the present-day realities three decades after the U.S. Food and Drug Administration (FDA) issued its 1993 Gender Guideline calling for assessments of medication responses in both sexes and revoking an earlier recommendation to exclude women of childbearing potential from early clinical studies. Patricia Larrabee, chief executive officer of Rochester Clinical Research, and Sans Thakur, chief growth officer of Medable, both have a first-hand view of the situation over much of that time span. 

Larrabee, a nurse practitioner by training, 29 years ago founded what is now one of the largest independent research sites in the country with 80 employees and a dozen investigators. She has found women overall to be much more willing to participate in most trials while men are more reluctant possibly due to the associated discomfort with study procedures such as blood draws. The ratio of women to men in a study is typically 60/40 or even 70/30, depending on the study indication, she says. 

But many of the protocols also exclude women, Larrabee quickly adds, notably those who are pregnant or in their childbearing years due to the unknown effects of drugs on a fetus. That said, more trials today allow the enrollment of younger women if it can be verified that they are using highly effective contraception rather than excluding them outright. 

Thakur has been working in the life sciences for about 25 years and, prior to joining Medable in 2021, was global life sciences research lead at Accenture where she was heading up the life science industry’s COVID response to ensure patients retained access to studies. Medable offers an industry-leading platform for decentralized clinical trials (DCTs) that are becoming increasingly common in clinical research.  

As a sitting council member on the World Economic Forum, her take on women’s participation in clinical trials is that it correlates more broadly with the evolution of gender and health parity—or the lack thereof. Two-thirds of those currently suffering from Alzheimer’s disease are women, a far higher proportion of the women in randomized controlled trials of experimental drugs for the condition, says Thakur. 

Medicines on the market today are the result of a 10-year R&D cycle that began when women were more often excluded from clinical trials and “effectively don’t represent women equitably” in terms of their benefit, Thakur continues. Estimates are that it will take about 132 years to close the overall gender parity gap, a disconcerting reality given that “every human on this planet is born of a woman who [broadly speaking] isn’t receiving the right health services.” 

Until women are included in clinical trials at parity—meaning, better than 50/50 with diseases disproportionately affecting them—"we won’t be making medicines for them,” she says. How to execute on the FDA’s broad new diversity policy to appropriately grow the number of women in studies will remain difficult without a better understanding of what’s working to change the paradigm.   

Breaking Barriers 

On a practical level, there are any number of steps sites can take to make clinical trials more convenient and family-friendly for women, says Larrabee. At Rochester Clinical Research, these include toys in the waiting room, exam rooms big enough to accommodate a mom with kids, the provision of snacks, and staff who provide childcare during exams. 

When children were being recruited for COVID vaccine studies, the investigative team made sure site visits could be flexibly scheduled and the participants all received hero T-shirts, she says. The facility also has an extra person available to, as needed, take kids out of the exam room when it’s the mom who is making study visits. 

Rochester Clinical Research will additionally arrange for transportation via Uber Health if women are otherwise unable to get to the site, says Larrabee. If dad has driven the family’s only car to work, his spouse is unlikely to volunteer to travel by bus with multiple kids in tow. 

Thakur’s focus is on the results of women’s lower participation in trials, including exacerbation of diseases, epidemics, and adverse drug reactions (ADRs). In fact, women experience ADRs nearly twice as often as men. Women also account for an estimated 86% of expenditures for treating drug-related interactions because during trials the pharmacodynamics and pharmacokinetics of drugs in the female body were never properly investigated and still not well understood.  

DCT options would certainly help lift the burden of participation for women, Thakur adds. Virtual consent, for example, might save them a 100-mile-plus trip just to sign documents on-site. Yet worldwide adoption of DCTs—invariably, where part of the trial happens at a physical trial site—remains low. “Until it reaches a level of permanence, we are always going to find challenges with [digital technologies] playing well with humans and people at the sites.”  

In the Rochester area, the challenges in DCT adoption are related to the high poverty rate that tends to create participation barriers, says Larrabee. When her site quickly toggled to DCTs during the pandemic, sponsors who wrote the trial protocol asked for diversity, including the elderly, but did not consider the impact of that demand. The technology was still in early stages of development, so lacked consistency, and the populations they were trying to reach didn’t necessarily have the required data plan, Wi-Fi, or familiarity with technology. 

Sponsors generally supplied too-few eDiaries to go around and participants were therefore expected to use their own smartphone, she explains. They also wanted older people to participate and many of them weren’t good with technology and remembering their passwords, so the site hired folks to troubleshoot phone issues in lieu of a highly paid clinical nurse. “We went ahead and set up new email accounts to enable them to enroll.” 

Larrabee says sponsors offered to hire community nursing companies to send nurses direct to patients’ homes during the pandemic. However, this created an issue for investigators who had the additional work of training, delegation, and oversight with no systems in place to ensure compliance with applicable regulations and ethical standards.  

“DCTs are relatively novel and will continue to mature,” Thakur adds. “Ultimately, this goes back to ... unequal funding of the therapeutic categories that are most relevant to women, which rolls down to the investment in clinical development ... [and] the investment in clinical innovation ... and new methodologies for running clinical trials that are as supportive for women as they should be.” 

The industry also must embrace new ways of working, she adds. For example, in Medable’s partnership with CVS, steps have been taken to ensure appropriate investigator oversight of trials being conducted in nontraditional community settings. 

Politics of the day have had a significant and negative impact on women’s health in general, Larrabee says, including research funding. It doesn’t help that researchers are more often men who aren’t necessarily focused on women’s issues.  

Understanding Women 

Cardiovascular disease is one of the big therapeutic areas that has been monitored for decades, says Thakur, in pointing out that women account for over 49% who are affected but only about 40% of the participants in cardiovascular disease trials. “It is inequitable, but it is getting better.” 

The bigger problem, as Thakur sees it, is that epidemiologists are not effectively measuring many diseases impacting woman globally due to a lack of data. Up until recently, it also wasn’t required to rigorously collect demographic data on clinical trial participants to have a decent baseline for measuring progress—and to “deliver on the promise of precision medicine.”  

So, what can be done to improve the situation? Larrabee first mentions increasing general awareness of the issues that women face in trying to participate in studies as well as the importance of their inclusion. The practice of Rochester Clinical Research is to frequently survey patients to find out what they need and what impacts their ability to participate.  

And the motivation may not be for themselves but the next generation, she points out. When recently contacted about a respiratory syncytial virus (RSV) study, every young healthy woman contacted seemed to know someone—a baby, friend, or relative—who had become “quite sick” from an RSV infection. “That’s why they participate ... the altruism motivator is very strong in women.”  

“Access and awareness are what will ultimately tip the needle when it comes to patient choice or a patient’s ability to make a choice of being part of the making of medicine,” agrees Thakur. But the bigger task at hand, ahead of even knowing a trial will happen, is to better understand the challenges women are facing. 

“The data is very poor, globally, on what patients need,” she continues. “Even epidemiology data is flawed.” 

Trial-sponsoring companies need and want to know where women are and how to get to them faster, says Thakur. “We can’t even design a great protocol to get them into the trial or to give them the right awareness or to open up the access without some of that information.” 

Technology platforms will improve with time, along with data quality and integrity and societal trust in that data, she predicts. But better managing the overarching costs and burdens of making medicines right will require knowing women better and “educating them uniquely based on whether they’re in India or China or the U.S.” 

This is where Medable has a play. Its DCT platform connects patients, sites, and sponsors to enable direct source capture across 60 countries in 40 languages. 

Trial-sponsoring companies can thereby better understand who they are treating and leverage the digital data for future decision-making on similar studies, including the needs of women on their healthcare journey, says Thakur. But many trials are still using a 100-year-old clinical research process, so the shift to a new and different data platform won’t and shouldn’t happen overnight. 

Disjointed Technology 

At Rochester Clinical Research, some DCT elements have been used for well over a decade, starting with telehealth and the use of PalmPilots as eDiaries, Larrabee says. One of the biggest challenges is related to the fact that pharma tools are numerous and don’t communicate with each other or other site technology tools.  

One trial for women with hot flashes required participants to use two or three disconnected devices and the site another five or six, she cites as an example. “It is a bit of a nightmare for sites in terms of the burden of [using] different technologies that simply are not ready for prime time. Industry has been very, very slow in advancing technology ... 20 years behind any other industry in the world,” and Larrabee doesn’t expect significant progress on the access, ease of use, and integration fronts for another five to 10 years.  

To compensate, the site has been deploying mobile technology whereby study staff go to people’s homes, says Larrabee. It has also invested in a mobile van so study-related exams can be done at conveniently located churches and community centers. 

Even then, technology challenges remain. “Rural areas may not even have a consistent Wi-Fi signal,” she notes. “If you are paying for a technology, it has to work where you are” with the enabling infrastructure in place. 

Time will take care of some issues, she says. She has noticed over the past two years that the younger generation of digital natives coming out of college are much better at dealing with technology glitches and finding workarounds than even their 30- and 40-year-old tech-savvy counterparts.  

The wait may not be long, Thakur adds, given that 13 of the top 20 biopharma companies have made or are currently making an investment in digital technologies across all R&D areas. This is what will ultimately reshape medicine, and clinical trials, returning a net present value in the form of medicines that matter.