Abstract
INTRODUCTION: Recruitment and retention remain critical challenges in clinical trials, particularly in neurodegenerative diseases, which require large participant populations, rigorous screening, and prolonged follow-up periods. Care Access is a global research site management organization that operates clinical trial sites employing various operational models. This study evaluates the operational performance of Care Access site models-including traditional sites, hub-and-spoke, and decentralized community-integrated research (DCIR) sites-within a Phase 3 neurodegenerative disease trial, focusing on their relative efficiency in recruitment, randomization, and retention. The inclusion of multiple site models within the same trial presents a rare opportunity for direct comparison under uniform study conditions, providing unique insights into their respective advantages and challenges. By analyzing key site performance metrics and the role of innovative operational strategies, this study aims to identify effective approaches to enhancing trial efficiency and overcoming recruitment challenges to inform the design and conduct of future trials. METHODS: The trial involved 32 Care Access sites each employing one of these distinct operational models. Key performance metrics, such as participant screening rates, randomization rates, screen failure rates, and post-randomization discontinuation rates, were analyzed across (a) traditional, (b) hub-and-spoke, and (c) DCIR site models. We also compared the enrollment performance of Care Access to that of 196 non-Care Access sites using publicly available data. RESULTS: DCIR Sites demonstrated the highest recruitment efficiency, screening 20.61 participants per site per month and randomizing 0.79 participants per site per month, compared to 11.78 and 0.50 for traditional sites, and 12.20 and 0.45 for hub-and-spoke sites, respectively. Despite being newly established, and operating in a decentralized model, DCIR sites achieved post-randomization discontinuation rates (28.17%) comparable to those of traditional site models (26.28%), highlighting their effectiveness in maintaining participant engagement. All site models encountered high screen failure rates (~95%), consistent with Phase 3 trials for neurodegenerative diseases. Notably, a community-engaged, research-only facility achieved the lowest discontinuation rate (17.65%) among all sites, highlighting the potential of strong local engagement to significantly enhance retention and participation. Furthermore, when comparing Care Access sites with non-Care Access sites in this trial, Care Access sites achieved an average randomization rate of 15.6 participants per site, outperforming the 8.7 participants per site recorded by non-Care Access sites. Data quality, monitoring practices, and overall data integrity were consistent across all site models, supporting the reliability of findings across both decentralized and traditional approaches. This comparison highlights the effectiveness of the innovative operational framework and decentralized community engagement approach in overcoming traditional recruitment challenges and enhancing trial outcomes. DISCUSSION: DCIR sites exhibited superior participant screening and randomization efficiency while maintaining discontinuation rates comparable to traditional site models. This success was driven by a combination of innovative operational strategies, including decentralized community-based outreach mechanisms that expanded population access to research by bringing trials directly to populations that previously lacked access to clinical research. At the same time, this approach helped reach underrepresented groups, thereby improving both geographic coverage and trial generalizability while enhancing overall trial performance. Additionally, other innovations like the deployment of centralized remote research coordinators also played a role by streamlining remotely-conducted tasks, allowing site staff, in all site models, to focus on participant care and engagement. These findings highlight the effectiveness of a flexible, multi-model site strategy in addressing recruitment and retention challenges in large-scale Phase 3 neurodegenerative disease trials and suggest that this approach may extend to other therapeutic areas facing similar challenges.