Of Endpoints and Equipoise: Reforming Clinical Trials in Colorectal Polyp Resection.

Purpose of review: To review and assess current design approaches in endoscopic mucosal resection (EMR) trials, identify areas where traditional methodologies may limit relevance or generalizability, and propose a forward-looking framework that incorporates methodological innovations aligned with clinical and stakeholder priorities.

Recent findings: Despite major procedural advances in EMR, trial design has evolved more slowly - employing binary endpoints, limited patient and clinician input, and enrollment models often led by high-volume proceduralists. Critical design innovations, such as ordinal recurrence classifications, composite outcomes ranked by clinical severity, and proceduralist-aware statistical models can help to overcome these limitations. Introducing methodology such as generalized pairwise comparisons yielding a win ratio, while useful for analyzing hierarchical composite endpoints (HCEs), represent just one facet of a broader strategy. Drawing from innovations in cardiovascular and other procedural disciplines, this review highlights how diverse design elements can be adapted to the EMR space. Improving EMR trials demands a shift in trial architecture. By combining stakeholder-informed outcome hierarchies, advanced analytic methods, and strategies to mitigate operator bias, a modern framework capable of producing more meaningful, reproducible, and generalizable evidence is possible. This evolution in design reflects a necessary progression for procedural trials and sets the stage for a new standard in colorectal polyp resection research.