THE CASE FOR INCLUSIVE
COMMUNITY-BASED CLINICAL TRIALS
THE RISK OF INACTION
Clinical trials are the foundation of medical innovation, yet historically, they have not fully represented all populations that may experience disease differently. This lack of inclusivity undermines scientific validity, compromises treatment safety and efficacy, exacerbates health disparities, and impose a significant burden on the U.S. economy. Despite regulatory efforts, significant gaps remain in the participation of racial and ethnic minorities, women, older adults, rural populations, and individuals with comorbidities.
Authors
This white paper is jointly authored by Dr. Anthonise Louis Fields and Ms. Lorena Kuri
THE PROBLEM:
LACK OF REPRESENTATION IN CLINICAL TRIALS
Clinical trials in the U.S. have historically failed to reflect the full spectrum of disease manifestations across populations, impacting treatment safety, efficacy, and generalizability. This under-representation contributes to health disparities, limits drug effectiveness, and reduces the real-world applicability of research.
For instance:
- The FDA (2020) reported that 75% of clinical trial participants were White, while Black (8%), Asian (6%), and Hispanic (11%) groups were significantly under-represented
- Older adults, who account for 60% of U.S. cancer cases, represent only 24% of trial participants, creating gaps in understanding treatment efficacy.
- Women are under-represented in cardiovascular disease trials, comprising just 25-38% of participants despite heart disease being their leading cause of death
- Rural populations (19% of the U.S.) participate in less than 5% of clinical trials, limiting insight into disease progression and treatment responses.
Consequences of Underrepresentation
Scientific and Medical Gaps
Compromised Treatment Effectiveness
A pooled analysis of phase III first-line immunotherapy trials submitted to the FDA found only 1% of participants were African American. This under-representation limits understanding of treatment efficacy in this population and contributes to poorer outcomes (11). Genetic, metabolic and environmental factors influence disease risk, progression, and drug response, meaning a lack of broad representation can weaken trial credibility, increase adverse events, and compromise treatment effectiveness.
Missed Innovation
Overlooking genetic variation and living experience in biomedical research oversimplifies disease mechanisms, disregards critical environmental and epigenetic influences, stifles scientific discovery, and slows the development of more effective, widely applicable therapies.
Under-Researched Conditions
Diseases like sickle cell anemia, primarily affecting Black populations, remain under-studied, delaying advancements in treatment.
Health, Regulatory, and Economic Impact
Higher Healthcare Cost
Health disparities cost the U.S. $451 billion annually, and this was projected to increase to $1 trillion by 2040. Addressing these health disparities in the U.S. is now projected to boost the economy by $2.8 trillion by 2040, translating to a 9.5% increase in projected GDP growth.
Coverage of Ineffective Treatment
When clinical trials exclude key populations, drug performance becomes less predictable in those groups, resulting in insurers covering ineffective treatments, wasted resources, and delaying proper care.
Regulatory Pressures
The FDA and other global agencies have emphasized demographic data in drug approvals. Regardless of potential policy shifts, the scientific rationale remains strong, and growing public awareness ensures continued scrutiny, with patients, advocacy groups, and stakeholders advocating broader representation in clinical research.
Eroded Public Trust
The exclusion of large segments of the U.S. population erodes trust in medical research, leading to lower participation rates and widening health disparities. As awareness grows, and patients are increasingly calling for greater transparency in clinical triasls, with physician-patient discussions increasingly centering on the question: ” Was this tested on people like me?”
Worsening Health Disparities
Already underserved communities will experience even greater inequities, straining public health systems.
Addressing Barriers
To drive meaningful progress, the healthcare ecosystem and broader community must remain committed to overcoming systemic barriers to participate, including:
Access Barriers
Expanding trial sites in underserved areas, strengthining community-based healthcare services, growing the locally trained healthcare workforce, and providing financial and logistical supports to this expanded ecosystem.
Policy and Incentives Gaps
Reinforcing adherence to existing regulations while ensuring proportional prioritization of the needs of underserved individuals and communities disproportionately affected by disease.
Trust Issues
Foster meaningful and sustained partnerships with communities to build enduring trust, especially among populations that have historically experienced medical mistreatment.
Restrictive Inclusion Criteria
Revisiting restrictive trial criteria that exclude individuals based on age, comorbidities, or other factors.
Recommendations
Community Strategic Partnership Approach
Establishing clinical trials strategic partnerships with faith-based and community-based organizations as investigative sites empowers communities to take an active role in research. This model enables communities to participate in conducting clinical trials that align with their priorities. With the necessary knowledge and resources, this approach fosters transparency, promotes community investment, and ensures sustainable engagement in clinical research.
Build Community Capacity for Clinical Research
Companies committed to advancing inclusive research can go beyond traditional recruitment by investing in local infrastructure and develop community-based research capabilities. By supporting research centers in underserved areas and funding dedicated resources (such as training programs, research coordinators, and technology) companies can empower communities to conduct trials aligned with their needs. Organizations can establish exclusive partnerships, sponsor dedicated research teams aligned with their pipelines, and create long-term engagement models that ensure mutual value. Structuring agreements to emphasize strategic collaboration, knowledge-sharing, and aligned research agendas can foster innovation while preserving competitive advantage.
Innovative Recruitment Strategies
Utilize technology and decentralize trial models to improve accessibility. For instance, telemedicine and mobile health units can reach participants in remote or underserved locations.
Patient-Centric Trial Design
Design trials that consider the specific needs and circumstances of targeted populations, such as flexible scheduling and treatment in places they naturally congregate.
By implementing these strategies, stakeholders can work towards more inclusive clinical trials, leading to treatments that are safe and effective for all populations.
Conclusion
Clinical trials are a vital part of the healthcare continuum, advancing the development of effective treatments, particularly when standard care falls short. Limited participation weakens scientific validity, reduces treatment efficacy, erodes public trust, and raises ethical concerns. Policymakers, industry leaders, and researchers must collaborate to better integrate clinical research into the healthcare system, ensuring it remains a cornerstone of medical innovation and improved patient outcomes.
Reference
Carpten J. CRCHD establishes team of cancer equity leaders. Keystone Symposia on
Molecular and Cellular Biology. Published 2024. Accessed February 3, 2025. Available at: https://www.keystonesymposia.org/conferences/conference-listing/meeting/onpage-
program/a12025- Hughes-Halbert C. USC health researchers rise to the challenge of improving diversity in
clinical trials. Keystone Symposia on Molecular and Cellular Biology. Published 2024.
Accessed February 3, 2025. Available at:
https://www.keystonesymposia.org/conferences/conference-listing/meeting/onpage-
program/a12025 - American Cancer Society. Cancer incidence rate for women under 50 rises above men’s.
Published January 16, 2025. Available at: https://www.cancer.org/research/acs-research-
news/cancer-incidence-rate-for-women-under-50-rises-above-mens.html. Accessed
February 10, 2025. - Association of Clinical Research Professionals' Response to FDA Draft Guidance on
Diversity in Clinical Trials. Food and Drug Law Institute. Published January 2023.
Accessed February 3, 2025. - Winkfield KM, Albrecht TL, Breen-Norris SL, et al. Perceptions of Cancer Care and
Clinical Trials in the Black Community: Implications for Care Coordination Between
Oncology and Primary Care Teams. J Cancer Educ. 2017;32(3):558-566.
doi:10.1007/s13187-016-1054-4. - Groundbreaking' sickle cell disease treatment approved for NHS use in England.
Published January 31, 2025.
https://www.theguardian.com/society/2025/jan/31/groundbreaking-potential-cure-for-
sickle-cell-in-england-approved-for-nhs-use?utm_source=chatgpt.com. - Singh H, Kanapuru B, Smith C, et al. Enrollment of older adults in cancer clinical trials:
Recent trends and future implications. JAMA Network Open. 2022;5(10):e2236756. - Scott PE, Unger EF, Jenkins MR, et al. Participation of women in clinical trials
supporting FDA approval of cardiovascular drugs. Eur J Cardiovasc Nurs.
2024;23(2):107-120. - Charlton M, Schlichting J, Chioreso C, Ward M, Vikas P. Challenges of rural cancer care
in the United States. Oncol Pract. 2015;11(6):486-493. doi:10.1200/JOP.2015.006486 - Kittles RA, Borrell LN, Hudson JI, et al. Genetic ancestry as an effect modifier of
naltrexone in smoking cessation among African Americans. Pharmacol Biochem Behav.
2015;132:92-97. doi:10.1016/j.pbb.2015.02.011. - Winkfield KM. Building Trust Through Community Engagement in Cancer Care. Am J
Manag Care. Published June 2022. - Gondhowiardjo S, Dowlati A, Singh H, et al. Disparities in Enrollment of Black Patients
in Immunotherapy Trials: A Pooled Analysis of Phase III First-Line Immunotherapy
Trials. Oncologist. 2024;29(1):47-56. - Waidmann TA. Estimating the Cost of Racial and Ethnic Health Disparities. Urban
Institute; 2009 - Davis A. US health care can't afford health inequities. Deloitte Insights. Published
August 24, 2020 - Jha AK, Orav EJ, Zheng J, Epstein AM. The characteristics and costs of preventable
hospitalizations in the United States. Health Aff (Millwood). 2004;23(6):239-249 - Lack of Diversity in Clinical Trials Costs Billions of Dollars: Incentives Can Spur
Innovation. USC Schaeffer Center for Health Policy & Economics. Published August
12, 2020. Available at: https://healthpolicy.usc.edu/article/lack-of-diversity-in-clinical-
trials-costs-billions-of-dollars-incentives-can-spur-innovation/?utm_source=chatgpt.com. - Barriers to Representation of Underrepresented and Excluded Populations in
Clinical Trials. National Academies of Sciences, Engineering, and Medicine. 2019.
https://www.ncbi.nlm.nih.gov/books/NBK584407/?utm_source=chatgpt.com. Accessed
February 10, 2025. Representation in Clinical Trials: A Review on Reaching Underrepresented
Populations in Research. Association of Clinical Research Professionals (ACRP). Published August 10, 2020. Available at: https://acrpnet.org/2020/08/10/representation-
in-clinical-trials-a-review-on-reaching-underrepresented-populations-in-
research?utm_source=chatgpt.com.
