Racial and ethnic disparities in u.S. chronic lymphocytic leukemia clinical trial enrollment: A participation-to-prevalence analysis

Abstract Background: Chronic lymphocytic leukemia (CLL) is the most prevalent form of adult leukemia in the United States, accounting for 20-30% of all leukemia cases. Ensuring equitable enrollment in clinical trials is essential for generating evidence that accurately reflects the diverse U.S. patient population. Participation-to-prevalence ratios (PPRs) serve as a valuable metric for assessing the representation of different racial and ethnic groups in cancer clinical trials. This measure is crucial for identifying disparities in access to clinical research opportunities, which can lead to biased outcomes and limit the generalizability of findings. Previous research conducted at a Northern California cancer center revealed significant underrepresentation of Black and Hispanic patients with CLL in clinical trials relative to their local and national disease prevalence. Methods: We conducted a retrospective analysis of 42 interventional clinical trials for CLL registered on ClinicalTrials.gov between 2015 and 2025, focusing exclusively on studies that enrolled adult participants in the United States. We systematically aggregated baseline demographic data, including race, sex, and age, from each trial to create a comprehensive dataset. To assess representation, we calculated PPRs for each racial group by dividing the proportion of trial participants from that group by their corresponding prevalence in the U.S. CLL population, using 10-year limited-duration prevalence data sourced from the Surveillance, Epidemiology, and End Results (SEER) program. A PPR between 0.8 and 1.2 is generally considered to indicate adequate representation, meaning the study population reflects the prevalence of the condition in the broader population. A PPR below 0.8 suggests underrepresentation, while a PPR above 1.2 indicates overrepresentation. This method allowed us to quantify disparities in clinical trial enrollment among different racial and ethnic groups. Results: Our analysis identified 42 U.S.-based trials that collectively enrolled 2,130 participants, yielding a median enrollment of 29 participants per trial. The demographic breakdown of the trial population was as follows: 77.6% White, 4.8% Black, 2.4% Asian, 0.4% Hispanic, 0.6% Native American, and 3.4% categorized as Other (including unknown or multiple reported races). Across all racial groups, there was an approximate 62% predominance of males, consistent with the sex-specific distribution of the disease. The calculated PPRs were 0.86 for White participants, 0.65 for Black participants, and 0.92 for Asian participants. These results indicate proportional representation for White and Asian patient populations, while the representation of the Black patient population is significantly lower. Although Hispanic and Native American participants were enrolled, PPRs could not be computed for these groups due to the absence of SEER prevalence estimates. Conclusions: Our analysis reveals that significant racial disparities persist in U.S.-based clinical trials for CLL over the past decade, with the largest underrepresentation among Black patients relative to their disease prevalence. Additionally, the enrollment of Hispanic and Native American participants remains seemingly low, and the lack of SEER data for these groups hinders our ability to quantitatively assess their representation. To address these disparities, it is imperative to implement targeted recruitment strategies that actively engage underrepresented populations. By doing so, we can enhance the diversity of clinical trial cohorts, thereby improving the generalizability of research findings. Ultimately, addressing these disparities is essential for ensuring that clinical research outcomes are relevant and applicable to the diverse CLL patient population in both the United States and around the world, fostering equitable healthcare advancements for all affected individuals.