What the research community has known for a long time recently became front-page news: Biomedical research has a diversity problem. Historically, clinical trials have enrolled primarily younger, white male participants. This has led to gaps in understanding treatment effectiveness in various populations and is also concerning from a health equity and public health perspective. Against this backdrop, the updated draft guidance on diversity in clinical trials issued by the FDA in June this year came as welcome news. Although the new guidance improves clarity and is stronger and more specific, it is not yet final. How, then, are sponsors and CROs responding to this situation? What will implementing diversity action plans (DAP) mean for sites, patients, and research in general? How are clinical operations and regulatory affairs teams applying this US-directed guidance in a global setting?
This panel, hosted by Vistatec’s Karen Tkaczyk, brings together a trio of experts from various organizations to decipher the real-world impact of the latest FDA guidance on clinical research.
Host
- Karen M. Tkaczyk, PhD, Director of Sales – Life Sciences, Vistatec
Panelists
- Lya Rebelo, Commercial Enablement Manager, Citeline
- Aman Khera, VP Regulatory Science and Innovation, Worldwide Clinical Trials
- Joan A. Chambers, Senior Consultant, Tufts Center for the Study of Drug Development (Tufts CSSD)
FDA Guidance – Background
Lya Rebelo of Citeline, who identifies as a Latina woman and “a chemist at heart” with an innate passion for diversity and health equity, anchored the conversation with a high-level overview of the evolution of FDA guidance on diversity. The 2024 draft guidance on diversity, which has just been publicized with some delay, was first mandated under the Food and Drug Omnibus Reform Act (FDORA), signed into law by President Biden in late 2022. Once the final guidance is released, likely in Q3 of 2025, sponsors will be required to submit DAPs for all phase 3 studies with protocols submitted within 180 days after publication of the guidance. This mandate and the new guidance are already actively shaping the future of clinical trials. Both propagate a concept of diversity beyond race and ethnicity to include age, sex, gender identity, and other demographic characteristics.
Clinical research, of course, does not stop to wait for FDA guidance. Therefore, many sponsors began to submit DAPs after the 2022 guidance was released. Now that another non-final guidance has been published, they lack a binding playbook, which Aman Khera calls “the gray zone.” This creates a new level of complexity for all stakeholders, who must move from a “check box exercise” to shifting their entire mindset around diversity and enrollment.
New OMB Race and Ethnicity Definitions
After receiving numerous comments on the difficulty of harmonizing and standardizing data in global studies based on race and ethnicity categories, the Office of Management and Budget released updated standards on collecting and reporting race and ethnicity in March 2024 that will apply to the new guidance. One of the key changes is combining the question of race and ethnicity into a single question. Multiple responses will be permitted in the future, and a new category, “MINA” (Middle Eastern or North African), has been added.
In the context of international trials, translating and applying these categories to participants in non-US countries is notoriously challenging. German speakers will know, for instance, that the direct translation of the term “race” is not acceptable, as it implicitly references biological racism. In addition, race and ethnicity categories frequently do not reflect or apply to a given region’s population.
Although the guidance applies exclusively to the United States in principle, collecting reliable data requires harmonization. This is made more challenging because different rules may apply in different countries. For instance, trial participants in Europe are not required to select a category for race and ethnicity.
Diversity + Health Equity
Regulatory agencies worldwide have also begun to address the issue of diversity, with EMA coining the term “diversity by design.” It is important to note that race and ethnicity are not the only characteristics that need to be considered to achieve diversity and inclusivity in clinical trial enrollment. Social determinants of health (SODH) such as income, education, access to transportation, and age must also be considered. This raises the question of bringing these disparate dimensions of diversity together when conducting global trials while ensuring a respectful approach to cultures and data privacy.
As Lya Rebelo argues, diversity is always about equity: “It’s not about ‘I want to have a seat at the table.’ I also want to be part of it. I also deserve to get the treatments that white male patients are getting.” The FDA guidance addresses this by encouraging sponsors to consider factors such as socioeconomic status, disabilities, comorbidities, geographic location, gender identity, sexual orientation, and pregnancy when developing enrollment goals.
In this context, crafting and submitting a DAP is only the beginning. This document is likely to go through multiple revisions, a process summarized by Aman Khera as “what you thought you were going to do, what actually happened, and how you’re going to move forward.” This then leads to the question of operationalization.
Burden on Investigative Sites
With the implementation of DAPs, investigative sites face added complexities: They will need to collect more demographic information and develop specific strategies to engage diverse populations. This added burden could potentially overwhelm staff already facing high workloads. From an operationalization perspective, this means that sites will need added resources in the form of staffing and improved communication around guidance. Partnerships with patient advocacy organizations can help provide training and support.
Ensuring diversity will also mean addressing things as basic as transportation and as complex as culturally sensitive communication and engagement strategies to build trust in communities. This is particularly true in communities with historically high levels of mistrust. Partnering with professional translation and interpretation service providers is critical to ensure culturally and linguistically appropriate communication with communities and persons of limited English proficiency. This serves not only to build trust and help patient communities learn more about clinical trials but is also mandated for obtaining informed consent, which is necessary to ensure data integrity.
Sponsors and Their Response
Clinical trial sponsors range from large pharmaceutical companies to small biotech firms. These differ as much in terms of their resources as they do in their response to the need for DAPs. While large sponsors are actively developing diversity teams and strategies, they continue to face challenges in defining what constitutes acceptable diversity outcomes. There is some pressure to balance transparency and data accuracy without creating excess complexity.
Smaller and medium-sized sponsors tend to face more limited budgets. Outsourcing and partnering with niche providers as well as CROs (Contract Research Organizations) can help these organizations implement diversity strategies. While they may lack dedicated teams, they can benefit from adopting best practices and making use of collaboration and relationship-building initiatives such as fostering long-term relationships and building trust with patient advocacy groups. This requires a longer-term rather than a transactional approach to demonstrate genuine interest in a community. Consistent, transparent engagement is necessary to gradually allay skepticism, especially in communities with a history of mistrust. Advancing diversity requires personal responsibility on behalf of everyone in the clinical research space, not just dedicated teams and experts – everyone needs to ask themselves what they can do to move the needle forward.
While sponsors’ abilities to implement diversity plans may vary, collaboration and relationship-building are key across the clinical research ecosystem.
The Role of Language Access
Much of what Vistatec does centers on advancing diversity through language access and cultural competency. Historically, those who did not speak English were often excluded from clinical trials. This has undergone a noticeable shift, with a growing recognition of the importance of language access in clinical trials. Both the FDA and other regulators are now encouraging the inclusion of diverse languages and translation services to facilitate participation. In addition to partnering with language service providers, hiring bilingual staff and interpreters can help facilitate this, and modern tools such as translation apps can – to a limited degree – help encourage participation and communication. Generally speaking, two-way communication between sites and sponsors is key to determining what resources sites need in order to successfully implement language access strategies.
Decentralization
Decentralized clinical trials can help increase diversity and inclusion by improving accessibility and reducing the burden of travel. However, this requires careful planning: Decentralization can refer to multiple approaches, from choosing diverse and accessible sites to allowing for home-based, local, or telehealth-based assessments or using technology such as wearables. In addition to patients, families and caregivers also have a role in the clinical trial process and must be appropriately supported. It is noteworthy that the new guidance has highlighted the need for regulation to drive diversity, which underscores systemic issues and a lack of measures that should already be in place.
Consequences and Challenges
After an extensive discussion, it was time for audience members to have their say. Asked what they believed would be the most significant consequence of the FDA guidance, most respondents agreed it would improve enrollment of participants from underrepresented communities. There was less consensus regarding the major challenges, with answers evenly split across three options:
- Data standardization for global studies
- Working on I/E criteria and avoiding protocol amendments
- Accessing social determinants of health to inform recruitment strategies
Conclusion
The FDA’s guidance on Diversity Action Plans (DAPs) is viewed as a powerful catalyst for change in how trials are designed and conducted. Although DAPs represent just one aspect of health equity, they serve as a much-needed disruptor that encourages a forward-thinking approach to enhancing diversity and inclusivity in research. By fostering accountability, the new guidance will help ensure that treatments are effective and safe for diverse populations, including future generations.
However, achieving true diversity in clinical trials requires more than compliance. Proactive education and guidance are necessary, especially for sponsors unfamiliar with current regulations and best practices or those based outside the US. Language access, also highlighted in the draft guidance, is critical for ensuring that communities with limited English proficiency fully understand trial processes, meet consent requirements, and build trust. CROs can play a crucial role by helping sponsors allocate resources effectively and tailoring effective outreach strategies that meet the needs of diverse communities. Even before the release of the final guidance in 2025, the draft guidance is already driving a much-needed mindset shift, ensuring that sponsors take a proactive rather than a reactive approach to clinical trial diversity.