Pragmatism in academic gastrointestinal cancer clinical trials: An analysis of trials conducted by the EORTC gastrointestinal tract cancer group and the unicancer gastrointestinal group.

INTRODUCTION: Pragmatism in trials improves their generalizability while reducing complexity through the conduct under real-world conditions with broader patient inclusion. This is particularly critical for gastrointestinal cancers (GI), which are among the most frequently diagnosed tumors worldwide and have one of the highest mortality rates. MATERIALS AND METHODS: We investigated all 19 GI clinical trials performed by the European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Tract Cancer Group and the Unicancer Gastrointestinal (UCGI) Group between 01/01/2010 and 31/12/2023. The level of pragmatism on the latest versions of protocols was assessed by two independent reviewers with the PRECIS-2 toolkit, which scores domains from 1 (very explanatory) to 5 (very pragmatic) covering 9 dimensions. RESULTS: Eligibility was predominantly restrictive (84% scored 1-2), often excluding patients based on ECOG > 1, organ dysfunction, comorbidities, or age. Trial settings ranged from single-country academic centers to international, multi-center designs. Organisation scores varied with more explanatory requirements for additional sampling or centralized assessments. Flexibility in delivery and adherence was moderate. Follow-up was frequently more intensive than routine care. Primary outcomes were mainly PFS/DFS (42%) or OS (21%); no trial combined OS with patient-reported outcomes. Primary analysis was often pragmatic with intention-to-treat analysis (74% scored 5). CONCLUSION: The PRECIS-2 tool offers a structured framework to guide improvements and support more pragmatic designs. Broader eligibility, greater treatment flexibility, focus on patient-centric endpoints, and streamlined organisational demands could enhance applicability of GI trial results to everyday clinical practice.