Trends and Characteristics of Clinical Trials Participation for Inflammatory Bowel Disease in the United States: A Report From IBD Partners.

Background And Aims: There are currently several recruitment challenges in randomized controlled trials (RCTs) for inflammatory bowel disease (IBD), which prolong the drug approval process and affect the generalizability of study results. The purpose of this study is to characterize individuals who participate in IBD RCTs and identify factors that could influence future recruitment strategies.

Methods: We performed a cross-sectional study within the IBD Partners cohort comparing patients with current or prior participation in an RCT of medical therapy for IBD to those without any RCT participation. Bivariate statistics were used to compare RCT participation by IBD subtype and by other demographic and disease characteristics, and predictive modeling was used to identify factors predictive of RCT participation. We calculated the percent of the cohort that participated in an RCT during each calendar year from 2011 to 2018 and accessed Clinicaltrials.gov to determine the number of active RCTs for IBD therapies per year during that same period.

Results: A total of 14,747 patients with IBD were included in the analysis and 1116 (7.6%) reported RCT participation at any time. Demographic factors predictive of RCT participation included following at an academic institution [odds ratio (OR) = 1.8; 95% confidence interval (CI) 1.51-2.04) and age 36-75 (OR = 1.7; 95% CI 1.46-1.92). Patients with Crohn's disease were more likely to participate than those with ulcerative colitis (OR = 1.5; 95% CI 1.35-1.77). Patients with more severe disease were more likely to participate, including those with prior IBD-related hospitalization (OR = 2.6; 95% CI 2.19-2.99), IBD-related surgery (OR = 2.5; 95% CI 2.24-2.87), biologic exposure (OR = 3.2; 95% CI 2.76-3.65), and "Poor" or worse quality of life (OR = 1.7; 95% CI 1.45-1.93). Steroid-free remission was associated with a lower likelihood of RCT participation (OR = 0.6; 95% CI 0.53-0.70). Although the number of active RCTs for IBD more than doubled between 2011 and 2018, RCT participation rates during that same time period decreased from 1.1% to 0.7% of the cohort.

Conclusions: RCT participation declined within this cohort. Groups underrepresented in RCTs for IBD included younger patients, patients followed in community settings, and patients with more mild disease. The non-RCT group had mean disease activity scores that did not meet remission thresholds, demonstrating populations in need of alternate therapies for whom clinical trials could be an option. Given anti-tumor necrosis factor (TNF) exposure rates in this national cohort, studies should focus on anti-TNF failure populations. Investigators should make every effort to offer RCTs to all patients and network with community providers to increase awareness of RCTs.