Evaluation of eligibility criteria in randomized controlled trials for chronic lymphocytic leukemia over 15 years.

Abstract

e23024 Background: Efforts to address disparities in clinical trial participation have increased over the past 30 years. Strict eligibility criteria in phase III interventional trials may exacerbate these disparities, limiting access and raising concerns about generalizability. Chronic lymphocytic leukemia (CLL), the most common chronic leukemia in adults, primarily affects older individuals and those with comorbidities, emphasizing the need for inclusive research. This study aimed to explore changes in eligibility criteria for phase III interventional CLL trials over 15 years. Methods: Clinical trial data were obtained from ClinicalTrials.gov, focusing on Phase 3 interventional studies related to CLL. The search used "chronic lymphocytic leukemia," filtered for adults aged 18–64 and older adults aged 65+. Trials enrolling patients between January 1, 2004, and December 1, 2019, were included. Trial designs, endpoints, and eligibility criteria were primarily extracted from published protocols when available and supplemented with information from ClinicalTrials.gov. Studies not specific to CLL, those evaluating supplements or vaccines, lacking a control arm, being single-center, or without investigational products were excluded from the data analysis. Data were grouped into three periods (2004–2008, 2009–2013, 2014–2019), and one-way ANOVA was used to assess differences in average eligibility criteria across these periods. Results: A total of 103 clinical trials were identified, with 47 included in the final analysis. Most were industry-funded (37 trials, 81%), while 10 (19%) were non-industry-funded. Regarding treatment settings, 60% targeted untreated patients, 32% focused on relapsed/refractory patients, and 9% included both. Interventions included chemoimmunotherapy (40%), targeted therapies (21%), combined approaches (36%), and other types (2%). The average number of eligibility criteria increased over time: 23.86 (IQR 14; range 12–39) in Period 1, 32.05 (IQR 19; range 18–59) in Period 2, and 46.25 (IQR 26.5; range 13–70) in Period 3. One-way ANOVA confirmed a significant difference across periods (F = 7.35, p < 0.001), showing a significant increase in the average number of criteria over time. Conclusions: Over 15 years, the number of eligibility criteria in phase III interventional CLL trials significantly increased, nearly doubling from 23.86 (2004–2008) to 46.25 (2014–2019). While this may improve internal validity, it risks excluding older patients and those with comorbidities, who are most affected by CLL. These findings highlight the need to balance scientific rigor with equitable access to ensure generalizability.