By Deepak Behera, MD, president & chief executive officer, and Melissa Andrews, project manager, Adaptive Research Inc.

Calls from the FDA, patient advocacy groups, and industry leaders to improve patient access to clinical trials have grown increasingly urgent. These calls for democratization are not just about equity but also about science, because studies that underrepresent certain groups lessen the predictive quality of the results for those groups.

What Studies Say About Diverse Patient Enrollment

Enrollment efficiency and diversity data point to an industry still struggling. Williams et al. examined clinical trial invitation and participation in a nationally representative sample of U.S. adults and found that only 9% of Americans reported having ever been invited to participate in a clinical trial¹. Meanwhile, studies exploring cancer trial enrollment suggest that more than 70% of patients are willing to participate in clinical trials while fewer than 5% of patients with cancer participate in clinical trials.² These statistics indicate a clear disconnect between patient interest and participation. According to a 2023 IQVIA report, Black enrollment in mid- and late-stage clinical trials declined over the last 10 years, “with a 46% decline in U.S. Census indexed inclusion between 2018 and 2022.” In fact, their enrollment levels have never been proportional to their representation in national demographics. Hispanic inclusiveness hasn’t declined as significantly, but it too never reached representative levels. In 2022, Hispanic patients were enrolled in clinical studies at 53% of national demographic levels.

To improve enrollment, site selection is frequently invoked as a tactic by industry, government, and researchers. To tap into a broader, more representative, and appropriately diverse patient population, it will be helpful to look beyond the traditional academic medical centers and bring research into the community setting — where a significant majority of patients receive healthcare — rather than continue to put the onus on patients to visit the AMCs.

Community Trial Sites Enable More Diverse Enrollment

Where companies have employed non-academic sites as a strategy to improve diversity, they have met with success. Last year, Genentech announced positive results from its Phase 4 CHIMES trial evaluating ocrelizumab in Black and Hispanic/Latinx people with relapsing multiple sclerosis (MS). The results were less of a revelation than the company’s ability to complete the first-ever clinical trial exclusively in Black and Hispanic/Latinx people living with MS. The company attributed the trial’s success to the inclusion of a wide range of study sites, including AMCs, hospitals, outpatient clinics, community centers, and healthcare provider practices.

While employing strategies to reach beyond AMCs has been shown to work, the overwhelming majority of trials continue to ignore community settings³. Potential contributing factors to this include:

• AMCs have dedicated clinical trials offices that provide regulatory, administrative, and operational support that make study start-up easier for sponsors.
• Sponsors may feel intimidated by the perceived increase in administrative commitments they take on with multiple community sites (i.e., contracts, negotiations, feasibility studies, etc.).
• Sponsors may prefer to keep their studies with experienced sites because they lack the means to mentor first-time or infrequent investigators.

To demonstrate that even a small or midsize sponsor can complete a trial in the community setting — thus lowering barriers and potentially increasing economic, racial, and cultural diversity — we present a case study of a successful trial in a rare disease fully enrolled in the community setting. Rare disease presents an elevated level of difficulty, as expertise in these conditions often lies within specialized centers of excellence. The trial’s ability to successfully locate eligible patients and suitable investigators in the community setting shows that it’s possible to target other types of specific populations outside of rare diseases.

Community Investigators Augmenting AMCs: A Case Study

For a Phase 2 trial for an investigational agent in development for the management of a rare cardiac disease, the sponsor needed swift execution to make a timely strategic development decision. However, initiating the trial at AMCs, where these patients are typically treated, posed a significant time challenge due to the extensive bureaucracy involved.

To address this, we suggested and worked with the study sponsor to implement a hybrid approach by partnering with leading AMCs. These rare disease experts, who usually manage these patients, provided support with the standard-of-care procedures requiring specific expertise. Meanwhile, community physicians, serving as the trial’s investigators, conducted the trial procedures, including administration of the investigational agent, which did not necessitate rare disease expertise. We provided the turnkey research support needed by the community physicians, enabling them to be effective without imposing on the academic experts’ time and effort.

Thanks to the excellent coordination and prompt communication channels, a well-designed pathway for enrolling and managing patients through various trial processes, and removal of all logistical and administrative burdens from community physicians, the team received unsolicited gratitude from the sponsor, physicians, and, most importantly, the patients. Seeing s smile in the face of pain is our ultimate reward!

This approach is successful when community sites have proper clinical trial administrative support. We provided comprehensive training (e.g., GCP and HSP), regulatory guidance, and managed all logistics and administration to ensure the study was conducted compliantly.

The sponsor was able to engage three sites under a single contract, significantly shortening the study start-up timeline. Rapid recruitment, patient concierge services, and proactive site management further accelerated the study. In collaboration with the sponsor, we used multiple channels to reach eligible patients – through AMCs, engaging with patient advocacy groups, and spreading the word at both local and national chapters. We set up a hotline/email for patient volunteers to reach out, with a dedicated team to respond, answer questions, and guide them towards their best options for enrolling in the trial. We continued providing guidance and support for trial participants during and after the trial procedures until closeout.

In addition to study start up (regulatory, financial, legal and operational activities), we supported the community sites and physicians throughout the study with on-site research coordinators, helping patients navigate the study procedures, guiding physicians with study activities and documentation, ensuring adherence to protocol, and minimizing errors. Most importantly, we successfully conducted this rare disease trial in a community setting where patients felt comfortable, thereby enhancing the diversity of the trial pool.

Tips For Sponsors And CROs

Our experience highlights a few valuable lessons:

• Expand your horizons: Community practices treat a vast and diverse patient population and offer a unique opportunity to collect scientific evidence in relevant clinical and cultural contexts. Yet, they are an untapped frontier. Find ways to engage them in clinical trials. One approach, as demonstrated in this case study, is to consider how your investigational agent or device will potentially be used after receiving clearance and engage with those physicians to serve as investigators rather than rely on dedicated research centers.
• Collaborate, don't dictate: Build strong partnerships with community PIs, offering clear expectations and tailored support. Some investigators will have clinical trial experience and will only need administrative support while others will need training (e.g. GCP, HSP) and direct coaching about communication, documentation, and screening. In order to ensure success, it’s important to have an accurate assessment of each PIs needs on an individual basis.  
• Invest in infrastructure: As community sites are unlikely to have their own Clinical Trials Office or Clinical Research Coordinators, the Sponsor, CRO or a third party will need to plan to provide these resources regulatory guidance, or technology setup. Part of study planning will be ensuring these resources are in place, either directly or indirectly.
• Tailor expectations: Community sites will require significant training and guidance to conduct the trials in a GCP-compliant manner. An approach that accounts for the level of support present in AMCs (either provided directly through the sponsor or via enabling vendors or technologies) will reap more dividends.
• Partner with patients: Patient advocacy groups are invaluable for both finding potential participants and raising awareness among community physicians with whom they have a rapport. Outside of the rare disease space, other advocacy and community groups can provide the bridge to target patient populations

The Way Forward With Community Sites And AMCs

True diversity and efficiency in clinical trials demand fresh thinking in site selection. While challenges exist, our project demonstrates it's feasible —and beneficial — to include community practices. The FDA recognizes this, offering guidance and initiatives to support community-based research. The recent focus on hybrid/pragmatic clinical trial models and the FDA framework for real-world evidence (RWE) to harmonize real-world data further supports this approach. Decentralization in clinical trials offers a patient-centric approach, allowing patients to be met where they are, oftentimes in rural and community practices, which improves convenience and efficiency. This fosters a responsive, more diverse, and equitable patient pool, which empowers communities, improves resource allocation by removing many of the bureaucratic challenges academic sites face, and enhances overall health outcomes. With the right strategy and partnerships, sponsors and CROs can make this work for them, bringing new treatments to patients faster and more equitably.

References:

1. Williams CP, Senft Everson N, Shelburne N, Norton WE. Demographic and Health Behavior Factors Associated With Clinical Trial Invitation and Participation in the United States. JAMA Netw Open. 2021 Sep 1;4(9):e2127792. doi: 10.1001/jamanetworkopen.2021.27792. PMID: 34586365; PMCID: PMC8482053.
2. Ebrahimi H, Megally S, Plotkin E, et al. Barriers to Clinical Trial Implementation Among Community Care Centers. JAMA Netw Open. 2024;7(4):e248739. doi:10.1001/jamanetworkopen.2024.8739
3. The IQVIA Institute. (2023, February 15). Global trends in R&D 2023. IQVIA. https://www.iqvia.com/insights/the-iqvia-institute/reports-and-publications/reports/global-trends-in-r-and-d-2023

About The Author:

Deepak Behera, MD is co-founder and CEO of Adaptive Research, a company with a mission to democratize clinical trials by transforming community-based clinical practices and hospitals into clinical trial sites. Deepak began his industry journey as a medical director launching a product in Alzheimer’s disease, later expanding to full-time consulting and advisory roles, such as senior medical director, head of medical affairs, and chief medical officer across oncology, neurology, cardiology, and rare diseases. His industry experience ranges from guiding regulatory and clinical development strategies to commercial medical affairs launches as well as evaluating the clinical and market potential of in-licensing and investment opportunities through clinical and regulatory due diligence.

Deepak volunteers on the advisory/executive committees of various non-profit organizations at the intersection of healthcare and technology and is also an advisor to pharma/biotech startups. Deepak and his family make their home in the San Francisco Bay Area.

Melissa Andrews joined Adaptive Research Inc. in 2022, where she holds the positions of project manager and certified nuclear medicine technologist. Prior to that, she worked as a consultant at Medical Imaging Consultancy. She also has an extensive tenure at the Biomedical Research Foundation of NW Louisiana, where she served as a nuclear medicine technologist from September 2005 to July 2022. Melissa attended the University of Arkansas for Medical Sciences.