Across 310 European CTIS Phase II and Phase III gastroenterology trial entries, safety/adverse-event endpoints were the most frequent overall, appearing in 195 entries (62.9%). Patient-reported outcomes and quality of life followed in 175 entries (56.5%), while biomarker/laboratory/inflammation endpoints appeared in 146 entries (47.1%). The endpoint strategy is strongly disease-shaped: inflammatory bowel disease trials concentrate on clinical remission and endoscopy, while GI oncology trials concentrate on survival, safety, and tumor response.
Safety/adverse-event endpoints appeared in 195 of 310 entries (62.9%), patient-reported outcomes or quality-of-life endpoints in 175 (56.5%), and biomarker/laboratory/inflammation endpoints in 146 (47.1%). These were the three most common endpoint families across European gastroenterology Phase II and Phase III trials.
European gastroenterology endpoint packages are not driven by one disease-specific measure. They combine safety, patient-reported burden, laboratory biology, and disease-specific efficacy signals, which is important for CTIS/EU submissions because endpoint descriptions often need coordinated clinical, eCOA, laboratory, imaging, and safety documentation.
Primary endpoints were split between safety/adverse events (67 of 310, 21.6%) and clinical remission (65, 21.0%). Secondary endpoints were more expansive: patient-reported outcomes or quality of life appeared in 168 entries (54.2%), safety in 146 (47.1%), and biomarkers/laboratory/inflammation in 118 (38.1%). Exploratory endpoints were uncommon, led by biomarker/laboratory/inflammation endpoints in 8 entries (2.6%).
The primary endpoint layer is narrower and more confirmatory, while secondary endpoint layers carry much of the patient-experience, safety, laboratory, and operational measurement load. Exploratory endpoint fields were present but sparse, mainly used for biomarkers and mechanistic follow-up.
The largest disease groups were GI oncology with 108 entries (34.8%), inflammatory bowel disease with 102 (32.9%), and liver/biliary/metabolic disease with 46 (14.8%). IBD was remission/endoscopy-led, GI oncology was survival/response-led, and liver/biliary/metabolic trials were biomarker/laboratory-led.
A single “gastroenterology endpoint strategy” is too broad for CTIS planning. IBD submissions need strong remission, endoscopy, and disease-score definitions; GI oncology submissions need survival, tumor response, and safety definitions; liver/metabolic submissions need laboratory, biomarker, imaging, and histology clarity.
The largest sub-disease groups were ulcerative colitis (50 entries), Crohn’s disease (47), colorectal/rectal cancer (50), pancreatic cancer (20), esophageal cancer (19), and MASH/NASH (14). Crohn’s disease had the strongest endoscopy signal at 41 of 47 entries (87.2%), while MASH/NASH had the strongest biomarker/laboratory signal at 12 of 14 entries (85.7%).
| Sub-disease | Entries | Most frequent endpoint families |
|---|---|---|
| Ulcerative colitis | 50 | Clinical remission 38 (76.0%); disease activity 34 (68.0%); endoscopy 31 (62.0%) |
| Crohn’s disease | 47 | Endoscopy 41 (87.2%); clinical remission 38 (80.9%); disease activity 33 (70.2%) |
| Colorectal / rectal cancer | 50 | Survival/event-free 36 (72.0%); safety 34 (68.0%); tumor response 23 (46.0%) |
| Pancreatic cancer | 20 | Safety 17 (85.0%); survival/event-free 15 (75.0%); surgery/rescue care 11 (55.0%) |
| Esophageal cancer | 19 | Safety 13 (68.4%); survival/event-free 13 (68.4%); tumor response 12 (63.2%) |
| MASH / NASH | 14 | Biomarkers/labs 12 (85.7%); histology 9 (64.3%); imaging 7 (50.0%) |
The most operationally demanding sub-disease endpoint sets differ sharply: Crohn’s disease requires central endoscopy and disease activity rigor; ulcerative colitis emphasizes remission and Mayo-based disease scoring; MASH/NASH depends on biomarkers, histology, and imaging; GI oncology depends on survival and response frameworks.
The dataset included 157 Phase II entries and 153 Phase III entries. Phase II was more safety-heavy, with safety/adverse-event endpoints in 113 of 157 entries (72.0%); Phase III was more balanced, with safety in 82 of 153 entries (53.6%), PRO/QoL in 80 (52.3%), and biomarkers/labs in 66 (43.1%).
Phase II gastroenterology trials place more emphasis on safety, laboratory biology, PK/PD, and mechanistic endpoints. Phase III trials shift toward clinically interpretable outcomes such as remission, disease activity, surgery/rescue care, and sustained patient-reported benefit.
Small molecules were the largest modality group with 138 entries (44.5%), followed by monoclonal antibodies with 57 entries (18.4%) and monoclonal antibody plus small-molecule combinations with 40 entries (12.9%). Monoclonal antibody entries were strongly IBD-shaped, with clinical remission and endoscopy each present in 32 of 57 entries (56.1%).
| Modality | Entries | Most frequent endpoint families |
|---|---|---|
| Small molecule | 138 | Safety 96 (69.6%); PRO/QoL 83 (60.1%); biomarkers/labs 67 (48.6%) |
| Monoclonal antibody | 57 | Clinical remission 32 (56.1%); endoscopy 32 (56.1%); PRO/QoL 27 (47.4%) |
| mAb + small molecule | 40 | Safety 32 (80.0%); PRO/QoL 28 (70.0%); survival/event-free 28 (70.0%) |
| Peptide/protein/enzyme | 29 | Safety 18 (62.1%); biomarkers/labs 16 (55.2%); PRO/QoL 14 (48.3%) |
Modality effects largely reflect disease mix. Monoclonal antibody programs are concentrated in IBD-like remission/endoscopy packages, while small-molecule and combination programs span broader safety, PRO/QoL, biomarker, survival, and tumor-response endpoints.
Endpoint complexity is a major CTIS/EU submission issue in gastroenterology. The data contain 182 entries authorized in 2024 (58.7%), 101 in 2025 (32.6%), and 27 in 2026 (8.7%). Across all years, 175 entries (56.5%) included PRO/QoL endpoints, 146 (47.1%) included biomarker/laboratory/inflammation endpoints, 81 (26.1%) included endoscopy endpoints, and 68 (21.9%) included PK/PD endpoints.
For European gastroenterology submissions, endpoint readiness is not only a protocol-writing issue. It affects CTIS consistency across Part I documentation, eCOA deployment, central lab setup, endoscopy/pathology reads, safety reporting, and country/site feasibility.
The same endpoint/context data also show where endpoint execution is likely to be more operationally complex across pediatric, orphan, and modality-defined trial groups.
The highest operational burden appears when pediatric, orphan, IBD, and biomarker-heavy programs intersect. These submissions need earlier alignment on endpoint wording, assessment schedules, instrument licensing, central services, and country-level CTIS consistency.
AE/SAE/AESI: adverse event, serious adverse event, adverse event of special interest. CTIS: Clinical Trials Information System for EU/EEA clinical trial submissions. IBD: inflammatory bowel disease. PRO/QoL: patient-reported outcome / quality of life. CDAI/PCDAI: Crohn’s Disease Activity Index / Pediatric Crohn’s Disease Activity Index. SES-CD: Simple Endoscopic Score for Crohn’s Disease. RECIST: Response Evaluation Criteria in Solid Tumors. OS/PFS/ORR/DCR/DOR: overall survival, progression-free survival, objective response rate, disease control rate, duration of response. PK/PD: pharmacokinetics/pharmacodynamics.