DE&I and Drug Safety: Surprising Connections to Improve Patient Health

Leesha: Specifically, from the perspective of the pregnant population… there’s a lot of work that can be done. It’s become quite a hot topic, particularly in the post COVID-19 era where a lot of pregnant people and their healthcare providers had no data on whether it was safe to provide vaccines to this population, and/or whether it would be effective for them. Many of them were left confused and concerned.

Over 200 million women become pregnant per year, with many of these women being prescribed a medication to use while pregnant. However, over 80% of these clinical trials routinely exclude pregnant populations.

What barriers does the industry face when seeking to include pregnant people in clinical research?

Erin: One barrier that I often hear cited is an unwillingness of diverse populations to participate in clinical research. However, a 2021 study showed that 75% of black and Latinx residents expressed a willingness to participate in clinical research. Yet over 90% of this study’s population had never even been approached for participation.

It is important that we take an evidence-based approach to identifying the true barriers to diverse populations joining clinical research. In my opinion, the true barriers that come to mind are:

• Strict eligibility criteria
• Costs related to clinical trial participation
• Limited community outreach
• Implicit English-language prerequisites
• Systematic disparities in healthcare access

Leesha: We are seeing a similar situation with pregnant populations, which is a direct result of the thalidomide disaster of the 1950s and 60s. The resulting birth defects from thalidomide use contributed to legislation that can routinely exclude women from clinical trials to protect them. I would say the biggest barrier is regulatory legislation not allowing us to perform research, when appropriate, on pregnant people. Whether or not they are included in the research, women still take these drugs during pregnancy and there is not data to inform them on potential risks to themselves or the fetus.

As Erin said, another barrier is the lack of education and awareness resources available. The existing policies are making decisions on behalf of patients, listing women as a vulnerable population. Ultimately, these are intelligent people who should have autonomy in their own medical decisions. They can make informed decisions if they are provided with the information.

What are some recent successes?

Erin: Many groups have generated substantial quantitative data that highlight the extent of issues concerning underrepresentation in research. Yet, there is a significant absence of data regarding the factors contributing to the successful representation of clinical researchers themselves. This data is crucial for the development of robust science of inclusion, leading to the development of effective clinical trial strategies.

There are some other notable achievements. The U.S. Food & Drug Administration’s (FDA) annual Drug Trials Snapshots show gradual improvement through increased awareness and action in regards to diversity and inclusion post-COVID.

Leesha: With respect to the pregnant population, we have seen some changes in recent European Medicines Agency (EMA) and International Council of Harmonisation (ICH) guidelines to help organizations better understand how and when it is appropriate to conduct research with pregnant people. This updated guidance is beneficial to the industry and, ultimately, the patients receiving these medications.

What considerations should organizations have in mind when designing an inclusive trial?

Erin: There’s always buzz about innovative protocol designs. But at the core of designing an inclusive trial is a substantial commitment of time, effort, and resources. A consistent and ongoing investment in these populations, rather than transactional efforts aimed at fulfilling study enrollment targets, will help to establish and restore trust. Investment should also extend to the technologies and systems that can alleviate patient burdens and enhance physical accessibility.

Biopharma organizations should allocate resources towards cultivating a diverse workforce that mirrors the diversity of global populations. It not only impacts personnel at study sites or between PIs and patients, but also gives us an opportunity to influence research questions that emerge, determine which research we focus on, and equip ourselves to better address health disparities or inequities. Approaches should be both bottom up and top down.

Leesha: I completely agree with that. It cannot be a “tick the box” exercise. These efforts need to be built into an organization’s operating frameworks to have meaningful inclusion. For pregnant populations, the industry should think about how to engage with external organizations that advocate for the inclusion of pregnant women in clinical trials. How can we take some of their learnings and apply them to how we run our trials?

In addition to the typical questions asked when designing a clinical trial, sponsors should consider what is appropriate to study in this population. For example:

• Is this going to be an indication that pregnant women would receive medication for?
• Are we seeking to treat an indication that is a problem in pregnancy (i.e., mastitis) or is it a chronic condition that occurs during pregnancy?

What needs to change to drive progress for under-represented groups in both clinical trials and drug safety?

Erin: It’s twofold. In addition to the practical approaches, there is a larger aspirational vision that embraces a fundamental shift in perspective. This entails transferring the locus of power from institutions to the community’s priorities and interests.

I think a true clinical trial model should actively pursue justice through transparency, accountability, and invested resources into these communities and through outreach programs. This will require a cultural mindset shift, policy changes, and the transparency and trial awareness education Leesha mentioned before.

Leesha: Yes! A mindset shift is needed in treating pregnant populations as well. We are not actually protecting women by not including them in clinical trials. We are potentially exposing them to harm. Truly protecting this population comes via including them in clinical trials and generating data from their participation. The FDA’s task force on Research Specific to Pregnant Women and Lactating Women (PRGLAC) is currently an advocate for this in the U.S.

What innovative or novel approaches do you think are a critical path for designing more inclusive clinical trials?

Erin: In my role as U.S. Innovation Lead, I have seen a huge influx of digital health technologies for remote monitoring, remote biomarker collection, artificial intelligence for patient recruitment, and hubs surrounding decentralized clinical trials.

At the end of the day, there is nothing more innovative and impactful than community outreach or partnering with existing grassroots efforts to reach key groups. There is no “one size fits all” approach for every single patient population. Patients want options.

Leesha: In my role, I am in support of a uniform consent process for enrolling pregnant women in clinical trials. Current legislation in the U.S. requires both parents to provide informed consent for any research to be done on a fetus.

A uniformed consent will help educate how these women will be monitored for adverse events, inform them on how to weigh information about potential effectiveness and safety[BP1] [HW2] , and encourage a dialogue to answer any ethical or legal concerns that they have.

How is TransCelerate progressing advancement in diverse and inclusive clinical trials?

Erin: Since I joined the Diversity of Participants in Clinical Trials Initiative in 2022, I have watched TransCelerate and its member contributors move beyond awareness and education to creating actionable tools and frameworks for organizations to implement. I am proud to be a part of creating these solutions.

Leesha: The IGR PV Initiative created a Points to Consider resource to help organizations know what current legislation exists around the world and what they need to consider when including pregnant or breastfeeding women in their clinical research.

TransCelerate has advanced advocacy through directly engaging global health authorities to share our findings, including gaps and ambiguities in the regulations, along with some suggestions to address them. We have received positive feedback from them and I’m proud and grateful to be a part of it.

Can you offer any parting advice?

Erin: Diversity and inclusion in trials is bigger than just ethics towards a moral good. It’s good science. Challenge the status quo and think larger than the individual or a site. How can we challenge the historical, institutional and social barriers that have shaped research accessibility in the past through our everyday work?

Leesha: Help change the current mindset. We don’t protect people by excluding them from clinical trials. We protect them by giving them the information they need to best inform their own healthcare decisions.

Erin Stackowitz is the U.S. Innovation Lead at Sanofi. She is responsible for finding digital and non-digital solutions that support clinical trials across all of Sanofi’s non-vaccine therapeutic areas.

Leesha Balramsingh-Harry is a Safety Data Acquistion Lead at Roche. She is responsible for monitoring safety data on platforms like social media, blogs, and other sources to ensure Roche is aware of all the potential additional sources of safety data that are being informally reported and may inform regulatory requests during drug applications.