Advancing Clinical Trial Design and Implementation in Resource-Limited Settings

Clinical trials are essential for developing new therapies and advancing medical knowledge since they produce the evidence for successful patient treatments. However, many trials face challenges such as complex study designs, restrictive eligibility criteria, and limited participation from underserved populations. These issues can slow enrollment, reduce the usefulness of results, and limit the benefits for patients, especially in resource-limited settings. Since 2008, Clinical and Translational Science Awards (CTSA) research has contributed important work to improve how trials are designed and conducted, and to make them more broadly applicable to patients.

Five key publications highlighted here were selected for their role in identifying barriers to successful clinical trial completion and their contribution to new medical policy, demonstrating the impact of CTSA-supported research over time.

CTSA-supported investigators have helped strengthen the methodological foundations of clinical trial design. The study Design and Endpoints of Clinical Trials in Hepatocellular Carcinoma (PMID: 18477802, 2008) provided widely adopted guidance on selecting appropriate measurements of outcomes and the right patient populations for liver cancer trials. By recommending standardized measures such as time-to-progression and overall survival, the work improved the consistency and comparability of clinical studies and has been cited in 18 policy documents, three patents, and 12 clinical trials, reflecting its influence on more successful clinical trial practices.

Research has also highlighted how trial eligibility criteria can unintentionally limit which patients can volunteer to participate. A study examining thoracic oncology trials (PMID: 28802905, 2017), which has been cited in two policy documents, found that eligibility requirements have become increasingly complex over time. While these criteria are intended to protect patient safety and ensure rigorous study results, excessive requirements can restrict enrollment and reduce how well trial findings apply to real-world patient populations.

CTSA-supported studies have also examined operational barriers that affect the recruitment of patients. Analysis of a multi-site randomized clinical trial that closed early due to low enrollment (PMID: 22155024, 2012) identified several factors that hindered participation, including complex protocols, limited staffing, and competing clinical studies and has been cited in a policy document. Understanding these barriers has helped researchers develop strategies to improve trial feasibility and participant recruitment.

In addition, CTSA-supported research has addressed the challenges of conducting trials in resource-limited areas. A study examining intervention research in disadvantaged communities (PMID: 23262157, 2013) identified barriers such as unstable living conditions, transportation limitations, and competing daily needs that can affect participation in clinical research. The study provided recommendations for adapting recruitment strategies and trial protocols to better support broad inclusion and has been cited in one policy and one clinical trial.

Finally, CTSA-supported research has examined the global distribution of benefits from clinical research trials. A cross-national analysis of trials supporting U.S. Food and Drug Administration drug approvals (PMID: 33950209, 2021), cited in one policy document, found that many trials enroll participants from middle- and lower-income countries, yet new therapies often become available much later—or not at all—in those same regions. These findings highlight the importance of policies that ensure the benefits of clinical research are shared worldwide.

Together, these CTSA-supported studies demonstrate how improving trial design, simplifying eligibility criteria, addressing recruitment barriers, and promoting participation can strengthen the clinical research enterprise and ensure that new therapies benefit more patients in a greater variety of clinical and resource settings.