Presentation (CTI)

OBJECTIVES: Randomized controlled trials often lack external validity, limiting their applicability to routine clinical care. The persistent absence of prospective, randomized real-world evidence (RWE) constrains clinical, payer, and policy decision-making. This study describes a pragmatic trial embedded within a US community gastroenterology network designed to generate robust, decision-relevant evidence.
METHODS: INSIGHT-IBD is a prospective, multicenter, cluster-randomized pragmatic study that will be conducted across 20 US community practices using a standardized clinical care pathway. Sites are being randomized to mirikizumab or other inflammatory bowel disease (IBD) indicated biologic therapy, preserving naturalistic prescribing and minimizing contamination. Approximately 400 adults with ulcerative colitis or Crohn’s disease initiating biologic therapy will be enrolled and followed for 18 months.
To reflect routine care, post-initiation treatment decisions remain at the physicians’ discretion. The primary end point is a composite measure of disease management escalation (e.g., treatment switching, dose escalation, IBD-related emergency visits or hospitalizations), capturing clinically meaningful outcomes and healthcare burden. Secondary outcomes include clinical remission, treatment persistence, concomitant medications, and patient-reported outcomes (PROs). Data are integrated from electronic health records (SoNaR-GI), claims, electronic case report forms, and PROs. Analyses will employ multilevel regression models to address clustering and confounding.
RESULTS: This study is expected to generate novel prospective, randomized RWE datasets evaluating biologic therapy within routine practice, enabling direct treatment strategy comparisons and quantification of real-world disease management burden. The study will produce actionable evidence on treatment effectiveness, care pathways, and variability across community settings to inform clinical, payer, and health technology assessment decision-making.
CONCLUSIONS: By embedding randomization within routine care, INSIGHT-IBD represents a necessary evolution in evidence generation, establishing a scalable, high-validity model that bridges the gap between clinical trials and real-world practice. Broader adoption of pragmatic, community-based study designs will be essential to inform guideline development, optimize care pathways, and accelerate value-based care.