From protocol design to site strategy, early-stage inclusion drives enrollment success, enhances data integrity, and improves health outcomes.

In clinical development, inclusiveness is too often treated like dessert: something optional, added at the end. But what if it were the main course from the start?

As clinical trials become more global and more visible, the demand for broad patient representation has shifted from a moral imperative to a scientific and commercial necessity. Yet despite growing awareness, many sponsors wait until Phase 3 to prioritize this approach when rigid protocols and entrenched site networks make the ability to adapt far more difficult.

For oncology and rare disease trials in particular, the opportunity lies upstream. By embedding equitable practices into early-phase development through protocol design, site strategy, and community engagement, sponsors can enhance data quality, accelerate enrollment, and position their trials for long-term success.

1. Designing for Inclusion Starts with the Protocol

The foundation begins with the protocol. Early-phase designs often include restrictive eligibility criteria, such as narrow lab value thresholds, language requirements, or exclusions for common comorbidities, that inadvertently eliminate large segments of underrepresented populations. While these criteria may be intended to protect patients’ safety, they can undermine broader inclusion goals.

Best practices from regulatory authorities emphasize that flexible, scientifically justified eligibility criteria can broaden participation without compromising safety or data integrity.[i] The National Institutes of Health’s All of Us Research Program exemplifies this approach: by embedding inclusive design principles from the outset, including broad eligibility criteria, multilingual outreach, and community partnerships, NIH enrolled a cohort where nearly 75 percent of participants came from historically underrepresented populations and nearly 50 percent identify as non-White or Hispanic/Latino.[ii] Likewise, designing trials that reflect real-world usage patterns, such as accommodating visit windows and home-based endpoints, helps ensure that diverse populations can participate and adhere to treatment.

Just as protocol design can widen the door for inclusion, where you place that door matters, too. That is where site strategy comes in.

 

2. Prioritize Community-Centered Site Selection

While many sponsors default to academic medical centers, most patients, particularly those from underserved backgrounds, receive care in community settings.[iii],[iv] Relying exclusively on large institutions may result in homogeneous populations and slower enrollment.

Instead, leading sponsors are expanding their footprint to include community health centers, minority-serving institutions, and rural hospital sites that reach diverse, underserved populations. Studies show community-based sites can increase minority enrollment by up to 40 percent compared to traditional academic centers.[v],[vi],[vii]

 

3. Build Relationships Before You Need Them

Trust is not transactional. Especially in rare diseases and oncology, where communities may be small, marginalized, or mistrustful of the research system, early and consistent engagement is crucial.6 Sponsors should partner with community-based organizations, churches, and advocacy groups well in advance of a trial launch.

These groups serve as trusted voices, capable of educating patients, co-creating outreach strategies, and surfacing concerns that might otherwise go unheard. Faith-based engagement has been shown to increase awareness and screening rates in underserved communities significantly.[viii],[ix],[x]

Partnering with organizations like the Akari Foundation, which have demonstrated that culturally resonant outreach led by community members and delivered in native languages helps overcome distrust and drive engagement in rare disease trials.[xi]

 

4. Make Communication Culturally Relevant and Linguistically Accurate

Language barriers and cultural mismatches are significant contributors to both low enrollment and early dropout rates. But the solution is not just translation; it is cultural localization. According to the NIH, trials using linguistically and culturally tailored materials achieved meaningful improvements in participant retention.6,[xii] Best-in-class sponsors co-develop materials with clinicians and native speakers, validate readability, and ensure visual and verbal elements reflect the patient’s lived experience.

Sponsors must go beyond literal translation:

  • Use in-language staff and clinicians to review all patient-facing content
  • Tailor visuals, tone, and messaging to reflect the cultural identities of target communities
  • Build separate educational paths for different language groups when needed

Employing a dual-path strategy for educational content, validating translated materials with clinicians and community representatives to ensure clarity, cultural relevance, and emotional resonance.

 

5. Track Progress and Course-Correct in Real Time

Intent is not impact. Sponsors that successfully operationalize inclusion treat it as a measurable performance driver, not a passive goal. This requires setting clear enrollment targets by race, ethnicity, gender, and age, and tracking progress in real-time. High-performing organizations embed relevant metrics into governance frameworks, define KPIs, and hold CROs accountable throughout the study lifecycle.[xiii]

 

 

Checklist for Clinical Development Teams Operationalizing Equity in Trials

Turning principles into practice requires a structured, repeatable approach. The following checklist distills the strategies outlined above into actionable steps that clinical development teams can implement from day one to embed representativeness throughout the trial lifecycle.

 

Protocol Design: Build for Inclusion

  • Engage KOLs and community clinicians early to identify barriers to participation
  • Use science-based eligibility criteria; avoid overly restrictive lab values or exclusions that disproportionately impact underrepresented groups
  • Design for real-world accessibility (e.g., flexible visit windows, telehealth, wearable devices, home-based assessments)
  • Incorporate translated, literacy-appropriate consent forms and educational materials from the outset

 

Site Selection: Think Beyond the Academic Medical Center

  • Select sites that include community health centers, rural hospitals, and minority-serving institutions
  • Prioritize locations with a proven record of serving Medicaid, uninsured, and multilingual populations
  • Evaluate cultural competency and local trust alongside performance metrics
  • Engage site staff early to tailor outreach strategies to local demographics

 

Community Engagement: Start Early, Stay Consistent

  • Identify patient advocacy organizations, community organizations, and faith-based partners at least 6 months before study launch
  • Co-create recruitment materials and education campaigns with these partners
  • Maintain consistent communication throughout the study to foster trust and transparency
  • Track and document engagement outcomes for future trial planning

 

Participant Communication: Prioritize Cultural and Linguistic Relevance

  • Develop culturally localized materials tailored to each target group
  • Validate content with native speakers, clinicians, and patient advisors
  • Use culturally relevant visuals, language, and messaging that resonate with lived experiences
  • Create multiple education tracks where needed to reflect linguistic and cultural diversity

 

Metrics & Monitoring: Make It Measurable

  • Define enrollment targets by race, ethnicity, gender, and age
  • Monitor demographic metrics in real time, starting with the first patient enrolled
  • Equip clinical operations to adjust recruitment strategies as needed
  • Embed appropriate KPIs into CRO/vendor contracts and performance reviews

 

Partner with Ergomed to Build Inclusive, High-Performing Trials

Ergomed’s experienced team helps sponsors operationalize diversity from the ground up, aligning with regulatory guidance, enhancing site performance, and co-developing culturally resonant educational materials that drive engagement and retention. Contact us to learn how we can support your program from protocol to close-out.

 

 

 

 

[i] U.S. Food and Drug Administration. (2020). Enhancing the Diversity of Clinical Trial Populations — Eligibility Criteria, Enrollment Practices, and Trial Designs.

[ii] Mapes, B. M., Foster, C. S., Kusnoor, S. V., Epelbaum, M. I., AuYoung, M., Jenkins, G., Lopez‑Class, M., Richardson‑Heron, D., Elmi, A., Surkan, K., Cronin, R. M., Wilkins, C. H., Pérez‑Stable, E. J., Dishman, E., Denny, J. C., & Rutter, J. L. (2020). Diversity and inclusion for the All of Us research program: A scoping review. PLOS ONE, 15(7), e0234962.

[iii] Tufts Center for the Study of Drug Development. (2023). The State of Clinical Trials. Tufts University.

[iv] Center for Information and Study on Clinical Research Participation. (2020). CISCRP Perceptions & Insights Study 2020.

[v] Scharff, D. P., et al. (2010). More than Tuskegee: Understanding mistrust about research participation. Journal of Health Care for the Poor and Underserved, 21(3), 879–897.

[vi] George S, Duran N, Norris K. A systematic review of barriers and facilitators to minority research participation among African Americans, Latinos, Asian Americans, and Pacific Islanders. Am J Public Health. 2014 Feb;104(2):e16-31.

[vii] Loree, J. M., Anand, S., Dasari, A., et al. (2019). Disparity of race reporting and representation in clinical cancer trials. JAMA Oncology, 5(10), 1392–1398.

[viii] Johnson, L. B., et al. (2015). A faith-based educational intervention to improve clinical trial participation among African Americans: A cluster randomized study. Journal of the National Medical Association, 107(5), 374–381.

[ix] Campbell, M. K., Hudson, M. A., Resnicow, K., Blakeney, N., Paxton, A., & Baskin, M. (2007). Church-based health promotion interventions: Evidence and lessons learned. Annual Review of Public Health, 28, 213–234.

[x] Schoenberg NE. Enhancing the role of faith-based organizations to improve health: a commentary. Transl Behav Med. 2017 Sep;7(3):529-531.

[xi] The Akari Foundation. (2024).

[xii] National Institutes of Health. (2022). Culturally and Linguistically Appropriate Services (CLAS) in Research.

[xiii] National Academies of Sciences, Engineering, and Medicine. (2022). Improving representation in clinical trials and research: Building research equity for women and underrepresented groups. The National Academies Press.