Trial of SiTes to IncreAse diversity in clinical TriaLs (TOTAL): A study protocol paper

The Trial Of Sites to Increase Diversity in Clinical Trials (TOTAL) addresses the critical issue of underrepresentation in cardiometabolic clinical trials. Despite existing initiatives, disparities in trial participant racial and ethnic diversity persist, limiting the generalizability of findings and health equity. This study aims to evaluate the effectiveness of three diversity-enhancing recruitment strategies (DERS)-virtual community ambassadors, population-based research registries, and social media ads-compared to usual recruitment methods. A hybrid implementation-effectiveness cluster RCT design will randomize 36 cardiovascular clinical trial sites across the US to one of these 4 arms. The main outcome assessed is the proportion of underrepresented participants pre- and during the intervention. Using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework, the study will assess recruitment effectiveness for historically underrepresented participants. Data collection includes de-identified demographic, screening, and enrollment information analyzed through robust statistical methods, including logistic regression and generalized estimating equations. Qualitative interviews with site teams will provide additional insights into implementation challenges and successes. The study aims to identify the most effective recruitment methods, refine these strategies, and disseminate findings to enhance future clinical trial diversity. The TOTAL study's findings will provide evidence-based recommendations for increasing representation in trials, addressing a long-standing barrier to equitable healthcare innovation. By improving diversity, TOTAL will contribute to the broader goal of ensuring that treatments are effective and safe for all populations, fostering inclusivity in scientific research, and advancing precision medicine. This research is supported by the American Heart Association, underscoring its importance in achieving health equity.