The number of IBD clinical studies grows each year; however, the number of patients enrolling in these studies has not increased proportionally. Instead, patient enrollment rates for IBD trials in recent years have shown a significant decline: from 1998 to 2018, the average recruitment rate in moderate-to-severe UC decreased from 0.32 to 0.13 patients per site per month, while the average recruitment rate in moderate-to-severe CD decreased from 0.65 to 0 to 0.10 patients per site per month.i
In PSI’s white paper Inflammatory Bowel Disease: Current Status and Future Perspectives, Senior Medical Advisor Maxim Kosov breaks down recent trends in IBD clinical research, including insights into patient recruitment and retention. Read on to discover the top four challenges to consider when enrolling IBD patients for your next trial.
1. Availability of Existing Treatments
The success of FDA-approved treatments, particularly vedolizumab in 2014, ustekinumab in 2016, and tofacitinib in 2018, often leads to a decreased patient enrollment rate in placebo-controlled randomized controlled trials. When the currently approved drug provides effective treatment with minimal side effects, patients will often opt for this method instead of enrolling in a study where they may receive a placebo drug. This is often a leading factor contributing to slow enrollment.
2. Competition Between Trials
3. Country and Site Selection
4. Screen Failure Rates
Over the past decade, screen failure rates in IBD trials have grown, approaching 50% in UC and 70% in CD, primarily due to failure to meet minimal endoscopic or biomarker criteria for active disease and a growing list of exclusionary concomitant medications. In PSI studies, we’ve seen a screen-out rate of 26-48% in UC and up to 64% in CD.
Some general recommendations to minimize screen failure and aid in patient enrollment rates include higher drug-to-placebo rates (such as a ratio of 2:1 or 3:1 rather than 1:1), broader use of patient-reported outcomes as the primary study endpoint, and optimization of study visits’ duration and complexity (including fewer procedures and endoscopies). Additional options for trial design include adding a long-term open-label extension for patients responding to therapy, and more involvement from the patient’s primary GI physicians at local hospitals and private practices. Primary care doctors see patients at the earlier stages of the disease course. There is a better chance that such patients are more likely to meet eligibility criteria than those admitted to larger hospitals or academic institutions, where the disease is often more severe and potential complications more frequent.
IBD patient recruitment and retention depends on the study protocol criteria and complexity, which must be scientifically sound to achieve the goals of the study as well as being attractive to patients. PSI provides a thorough review of the protocol by internal therapeutic area experts and harnesses the power of AI and machine-learning through our INTELIA ™ platform, combined with strong site relationships around the globe, to ensure your study meets enrollment goals. If you’d like to learn more about PSI can support your global Phase 2 and 3 IBD trials, click here.
i Harris, M. S., Wichary, J., Zadnik, M., & Reinisch, W. (2019). Competition for clinical trials in inflammatory bowel diseases. Gastroenterology, 157(6), 1457–1461. https://doi.org/10.1053/j.gastro.2019.08.020
ii Heyman, M., Terdiman, J., Lewin, S., Verstraete, S. G., & Mahadevan, U. (2022, November 7). UCSF inflammatory bowel disease clinical trials – San Francisco Bay Area. UCSF Clinical Trials. Retrieved November 21, 2022, from https://clinicaltrials.ucsf.edu/inflammatory-bowel-disease
iii Ng, S. C., Shi, H. Y., Hamidi, N., Underwood, F. E., Tang, W., Benchimol, E. I., Panaccione, R., Ghosh, S., Wu, J. C., Chan, F. K., Sung, J. J., & Kaplan, G. G. (2017). Worldwide incidence and prevalence of inflammatory bowel disease in the 21st Century: A systematic review of population-based studies. The Lancet, 390(10114), 2769–2778. https://doi.org/10.1016/s0140-6736(17)32448-0