Diversifying Diabetes Trials with DAPs, Omics, And Community Engagement
A conversation with Luke Twelves, MA, MB BChir, MRCGP, PGDipBA, general practitioner and medical director
More often than we’d like, clinical trials aren’t reflective of the populations they serve. Take type 2 diabetes. The CDC reports that 12.1% of Black people are affected by diabetes, but clinical trials are generally composed of 4%-7% Black participants. What that amounts to in this therapeutic area, as with many others, is trial data that doesn’t reflect the experiences of the patients sponsor companies are seeking to treat.
In this Q&A, general practitioner and medical director Dr. Luke Twelves emphasizes the importance of more inclusive clinical trials, discussing the role of -omics (or the study of biological fields such as genomics and proteomics) and the potential impact of FDA-mandated diversity action plans (DAPs) in achieving this goal.
Clinical Leader: Despite type 2 diabetes disproportionately affecting minority groups, a recent article published in Springer Nature confirmed that they are underrepresented in both government- and industry-funded type 2 diabetes trials. What do we know about the prevalence of type 2 diabetes in minority patients and those same patients’ inclusion in clinical trials?
Dr. Luke Twelves: Research consistently reveals significant disparities in both the prevalence of type 2 diabetes and the representation of minority populations in clinical trials. According to the CDC’s most recent National Diabetes Statistics Report, the age-adjusted prevalence of diabetes is as follows: 13.6% for American Indian or Alaska Native populations, 9.1% for Asian, non-Hispanic individuals, 12.1% for Black, non-Hispanic individuals, 11.7% for Hispanic individuals, and 6.9% for white, non-Hispanic individuals. Despite these stark differences in disease burden, studies published in journals like Springer Nature, Diabetes Care, and Diabetologia have consistently shown that minority participation in clinical trials remains disproportionately low. For instance, a study examining enrollment between 2007 and 2017 found that African Americans comprised only 4%-7% of study populations on average, while the U.S. Census estimates African Americans at 13.7%. Similarly, Hispanic participation rarely exceeded 6%, despite their population share of 19.5%. This underrepresentation is especially concerning given the disproportionate burden these populations bear in terms of diabetes-related complications and mortality.
While analyzing individual trial data and linking it to various health, race, and ethnicity data sets can be challenging due to gaps in data across sources, the overwhelming evidence still points to a clear conclusion: For many type 2 diabetes trials, recruitment rates of minority groups fall far below what would be expected if recruitment matched the disease prevalence rates within society.
Understanding that, what’s the importance of improved inclusion of minority patients in clinical trials? In other words, what’s at risk if sponsors don’t adapt to our enrollment goals?
The implications of inadequate minority representation in clinical trials go well beyond mere demographic disparities. As our understanding of the importance of -omics, including genomics, deepens, it is becoming very clear that the inclusion of a broad range of minority groups is essential for robust scientific research. Studies have shown that certain diabetes medications may have varying efficacy profiles across racial groups due to genetic polymorphisms that affect drug metabolism. Additionally, side effect profiles can differ significantly. Without sufficient representation in clinical trials, these variations may go undetected until after drug approval, potentially leading to suboptimal treatment recommendations for minority populations. Conversely, effective drugs with acceptable safety profiles may be rejected simply because the trials lacked sufficient diversity. The notable exception of this is the 2005 FDA approval of BiDil, the first drug approved specifically for a minority group. However, nearly 20 years later, debates continue around this approval. It remains the only example of this happening — possibly because of the paucity of research in minority groups.
Research published in the Journal of Clinical Investigation also has emphasized how social determinants of health, dietary patterns, and cultural practices can influence treatment adherence and outcomes. While the post-approval debates surrounding BiDil underscore the complexity of focusing solely on race, it should undoubtedly serve as a reminder of the importance of capturing more comprehensive data. Understanding these multifaceted factors requires more inclusive clinical trials, paired with improved data capture and analysis.
Ultimately, payers and patients must be confident that the drugs they use are both safe and effective and, consequently, cost-effective. Achieving this confidence can only be accomplished through more inclusive clinical trials.
The article mentioned that industry enrolls a smaller proportion of minority participants compared with white participants. Government trials fair a bit better. Why do you think that is?
Analysis across several journals, including the recent paper in Springer Nature, reveals a consistent pattern: minority enrollment is higher in government-sponsored trials compared to industry-sponsored studies in the U.S. Government-funded trials, particularly those sponsored by the NIH, typically achieve 15%-20% minority participation, while industry-sponsored trials often report less than 10%. Some aspects of the analysis are complex; for example, in the Springer paper, industry trials were not limited to those based in the U.S., and assumptions about ethnicity data were sometimes necessary. However, these factors do not significantly alter the overall conclusions drawn from the research.
It's important to consider the potential causes of these disparities, even if the exact percentages are subject to discussion around confidence intervals. Disparities may arise from several factors: NIH trials often include specific diversity requirements tied to funding, the trial sites selected may reach a more diverse population, and NIH-funded trials tend to have longer recruitment timelines, allowing for more extensive community engagement. In contrast, industry trials typically prioritize rapid enrollment and often rely on established research networks that historically serve predominantly white populations.
These challenges can be addressed with innovative recruitment strategies and strategic site selection, especially when both the sponsor and the CRO acknowledge the importance of diversity.
What strategies or approaches should sponsor companies use to improve the enrollment of racial minorities?
Evidence-based strategies for improving minority enrollment have emerged from several successful initiatives. The Jackson Heart Study, one of the largest and most successful studies of cardiovascular disease in African Americans, demonstrated the effectiveness of comprehensive community engagement. Their model, published in the American Journal of Public Health, highlighted the importance of building trust through sustaining a community presence, employing diverse research staff, and addressing practical barriers to participation such as transportation and scheduling flexibility. Similarly, the Hispanic Community Health Study/Study of Latinos has shown that culturally tailored recruitment materials, bilingual staff, and partnerships with community organizations can significantly enhance Hispanic participation rates.
The location of research sites is also critical. When assessing site feasibility, sponsors should not only consider the disease focus but also the patients served, incorporating assessments of ethnicity, race, and socioeconomic factors. Understanding relationships at the site is equally important. Scoring sites based on their proactive community outreach, education efforts, and relationship-building initiatives can help identify those most likely to engage diverse populations. It is crucial to emphasize to the site network the importance both sponsors and forward-thinking CROs place on these aspects when evaluating a site. Individual site recruitment strategies should then be integrated into a broader strategic recruitment plan aimed at ensuring balanced representation.
Trial staffing is also essential. Ensuring that trial teams are diverse and well-trained in cultural competencies that could affect participant engagement and progression is key. Additionally, patient-facing materials should be multilingual to accommodate the needs of diverse participants.
Effective diversity in trials goes beyond race, ethnicity, or language; it also requires CROs and sponsors to consider socioeconomic factors and adopt a respectful, participant-centered approach. For instance, in socioeconomically challenged areas with high levels of shift work or limited childcare, it may be necessary to provide transportation support, flexible scheduling, and adequate compensation to enable participants to afford to take time off work. After all, if someone is juggling multiple jobs and struggling to pay bills, they cannot afford to take time off unless that "lost" income is replaced by trial compensation.
Finally, while all these actions are vital, they will only be fully effective if key metrics are tracked and acted upon. Recruitment strategies and participant materials should be adjusted as needed to ensure the goal of a representative trial is achieved.
Finally, the FDA has published guidance requiring sponsor companies to begin developing DAPs for their clinical trials. What impact could DAPs have on sponsors’ efforts to design more equitable clinical trial enrollment for diabetes trials?
While the FDA’s requirement for DAPs is relatively recent, similar initiatives in other contexts provide valuable insight into their potential impact. The NIH’s Revitalization Act of 1993, which mandated the inclusion of women and minorities in clinical research, led to measurable improvements in trial diversity, though progress has been inconsistent. Research published in Contemporary Clinical Trials has shown that structured diversity planning can enhance minority recruitment when supported by adequate resources and accountability measures. The success of DAPs will likely depend on several factors identified in the literature, including clear metrics for success, enforcement mechanisms, and the development of standardized best practices for implementation.
The field of clinical trial diversity is continually evolving, with new research providing valuable insights into effective strategies for improving representation. Future studies will be crucial for evaluating the impact of current initiatives and identifying additional approaches to ensure that clinical trial populations more accurately reflect the demographics of affected groups.
While DAPs are likely to play an important role in driving improvements in diversity, it may ultimately be the growing recognition of the significance of -omics in treatment development and testing that will drive even greater change over the next decade. As the field of -omics uncovers increasing complexity, the movement toward truly personalized medicine may enable patients and clinicians to access treatments optimized specifically for their care. This progress may well surpass the simple (though critical) metrics covered by DAPs over the next decade, fostering a more comprehensive and nuanced approach to clinical trial diversity.
About The Expert:
Luke Twelves, MA (Oxon) MB BChir (Camb) MRCGP (Lond) PGDipBA (Durh), is a general practitioner as well as medical director at Lindus Health, where he combines strategic and operational initiatives. Previously, Dr. Twelves was the CEO of a healthcare provider providing dermatology, ENT, diagnostic, and general practice services to the National Health Service (NHS) in England.