Suggestions from American Gastroenterological Association Roundtable Meeting on Improving IBD Clinical Trial Design

The American Gastroenterological Association (AGA) recently published a summary of their roundtable meeting discussing current challenges and potential solutions for improving inflammatory bowel disease (IBD) clinical trial design. IBD includes Crohn’s disease and ulcerative colitis. Attendees of the two-day meeting included clinical trial investigators and coordinators, representatives from FDA trial sponsor representatives, patients and patient advocacy group representatives, and other stakeholders, including AGA staff members.

During interviews before the meetings,, attendees agreed that complicated exclusion and inclusion criteria, extended washout periods, the use of placebo controls, and complex trial procedures were significant barriers to IBD clinical trial recruitment. Roundtable participants identified challenges and discussed potential short- and long-term solutions. Discussions focused on the following three essential themes for IBD clinical trial design: improving trial efficiency, increasing clinical trial diversity, and examining alternative clinical trial designs.

For improving trial efficiency, the participants focused on adjusting drug washout periods and minimizing endoscopy burden. They agreed that long drug washout periods that typically range from 8 to 16 weeks are inconsistent with real-world clinical practice. Additionally, stopping treatment for extended periods can lead to worsening disease and render patients ineligible for the trial.

Instead, the roundtable members suggest determining a maximum blood drug concentration acceptable for trial entry and allowing a subset of patients to enroll in the trial with a shorter washout period.

IBD clinical trials often require numerous endoscopies for both initial screening and monitoring throughout the trial. These procedures are burdensome for patients and clinical trial sites alike. The group proposed using video-recorded routine care endoscopies and digitally stored biopsies for trial screening as a solution. They also recommended reducing the number of endoscopies required during the clinical trial or replacing them with noninvasive markers of disease activity.

The discussion also turned to broadening the presence of underrepresented groups in IBD clinical trials and expanding trial networks.

Increasing enrollment of more diverse groups in clinical trials would help mitigate disparities, promote equity in IBD care and treatment, and reveal differences in disease manifestation and treatment response in diverse populations, the roundtable members agreed. Proposed solutions include engaging trusted community organizations and patient advocates for trial recruitment, developing patient-centered communication and education that uses inclusive or translated language, and reducing logistical barriers to trial participation.

To expand trial networks, the group proposed sponsor-supported efforts to identify and include new trial sites and investigators that focus on underserved populations.

Lastly, when discussing alternative clinical trial designs, the meeting attendees agreed that the use of placebo-controlled trial designs and strict inclusion criteria significantly limit participation in IBD clinical trials. Solutions proposed include minimizing the number of participants receiving placebo in clinical trials and simplifying early escape criteria from the placebo study arm.

Citing previous research, the group noted that up to 74% of patients with ulcerative colitis visiting a referral center would not qualify for an IBD clinical trial due to stringent exclusion criteria. To expand the type of patients included in trials, the attendees proposed developing a consensus on patient-centered trial endpoints and designing sub-studies that evaluate endpoints specific for traditionally excluded groups.

The group also acknowledged other areas of importance, such as pediatric trial design, trial endpoints for patients with Crohn’s disease that is mild to moderate, and using real-world data to inform label.