P664 Analysis of Clinical Trial Screen Failures in IBD: Real World Results from the IOIBD
Vieujean, S.(1)*;Lindsay, J.O.(2,3);Rubin, D.(4);D’Amico, F.(5,6);Ahuja, V.(7);Silverberg, M.S.(8);Sood, A.(9);Yamamoto-Furusho, J.K.(10);Nagahori, M.(11);Watanabe, M.(12);Koutroubakis, I.E.(13);Foteinogiannopoulou, K.(13);Walsh, A.(14);Outtier, A.(15);Abreu, M.T.(16);Dubinsky, M.(17);Siegel, C.(18);Louis, E.(1);Dotan, I.(19);Reinisch, W.(20);Danese, S.(5);Peyrin-Biroulet, L.(21);
(1)CHU Liège- Sart Tilman, Department of Gastroenterology, Liège, Belgium;(2)Blizard Institute, Barts and the London School of Medicine and Dentistry, London, United Kingdom;(3)The Royal London Hospital- Barts Health NHS Trust, Department of Gastroenterology, London, United Kingdom;(4)University of Chicago, Medicine Inflammatory Bowel Disease Center, Chicago- IL, United States;(5)IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Department of Gastroenterology and Endoscopy, Milan, Italy;(6)Humanitas University- Pieve Emanuele, Department of Biomedical Sciences, Milan, Italy;(7)All India Institute of Medical Sciences, Department of Gastroenterology, New Delhi, India;(8)Toronto Immune and Digestive Health Institute, Toronto Immune and Digestive Health Institute, Toronto, Canada;(9)Dayanand Medical College and Hospital, Department of Gastroenterology, Ludhiāna- Punjab, India;(10)Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Inflammatory Bowel Disease Clinic- Department of Gastroenterology, Tlalpa, Mexico;(11)Tokyo Medical and Dental University, Department of Gastroenterology and Hepatology, Tokyo, Japan;(12)Tokyo Medical and Dental University, Advanced Research Institute, Tokyo, Japan;(13)University Hospital of Heraklion, Department of Gastroenterology, Heraklion- Crete, Greece;(14)Oxford University Hospitals NHS Foundation Trust and NIHR Biomedical Research Centre, Translational Gastroenterology Unit- John Radcliffe Hospital, Oxford, United Kingdom;(15)University Hospitals Leuven- KU Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium;(16)University of Miami Miller School of Medicine, Division of Gastroenterology- Department of Medicine, Miami- FL, United States;(17)Icahn School of Medicine, Division of Pediatric Gastroenterology and Nutrition, Mount Sinai- New York, United States;(18)Dartmouth-Hitchcock Medical Center, Inflammatory Bowel Disease Center- Section of Gastroenterology and Hepatology, Lebanon, United States;(19)Rabin Medical Center- Sackler Faculty of Medicine, Division of Gastroenterology, Tel Aviv, Israel;(20)Medical University of Vienna, Department of Internal Medicine III, Vienna, Austria;(21)Nancy University Hospital- University of Lorraine, Department of Gastroenterology NGERE INSERM U1256, Vandœuvre-lès-Nancy, France;
Background
Recruitment rates for phase 2b/3 randomized controlled trials (RCTs) in IBD have substantially dropped over time. Several steps are required prior to successful patient randomization. Initially the physician must propose a trial to a potentially eligible patient during a pre-screening process (step 1). This is followed by patient’s acceptance or refusal (step 2). Finally, after informed consent the patient undergoes trial screening to ensure they meet all eligibility criteria (step 3). Evaluating each step separately, this study aims to assess reasons why IBD patients are not included in RCT and patients’ outcome after screen failure (SF).
Methods
All IOIBD member physicians (n=58) were invited to participate. To assess steps 1 and 2, consecutive IBD patients in relapse for whom a treatment change was required were prospectively included over a 4-week period. Reasons that prevented the IBD physician offering a sponsored multicenter phase 2b/3 RCT (step 1) and reasons why the patient accepted or refused to participate (step 2) were assessed through a physician and a patient survey, respectively. Reasons for SF (step 3) from the last 6 months, including the 4 weeks of steps 1-2, were collected retrospectively.
Results
A total of 104 (59 male, 62 CD, mean age of 37.2 years) and 102 patients (58 male, 63 CD, mean age of 40.6 years) from 12 centers were included in steps 1-2 and 3, respectively (Tables 1 and 2). Among 104 patients in relapse for whom a treatment change was required, 41 (39.4%) were offered a RCT. Of the 28 who consented to RCT, 5 failed their screening (SF rate of 17.9%) and 23 were included. Main reason that prevent IBD physicians from offering an RCT (step 1) are shown in Figure 1. After receiving information about RCT, major reasons why patients accepted or refused to participate included the trust they had in their IBD specialist and the risk of being assigned to a placebo, respectively (step 2). Regarding 102 patients included in step 3, main reasons of SF were insufficient disease activity (n=37), concurrent infection (n=15) and dropout (n=12) (Figure 2). Half of SFs could have been avoided by thorough prescreening. After SF, 51 patients were treated with commercially available therapy, 14 were rescreened for the same RCT (after resolution of the issue leading to SF), no treatment was required for 14, 10 were referred to surgery and 6 were screened for another RCT (the outcome was unknown for 7).
Conclusion
This first multicentric study reported a SF rate of 17.9%. Insufficient disease activity and the risk of assigning the patient to a placebo seem to be barriers to inclusion. Half of SFs could have been avoided by better pre-screening. After SF, most of patients were treated with commercially available therapy.