Digital twins in IBD-bridging data, biology and trial innovation

Clinical Snapshot

Key Findings

• P Value: Not applicable — no statistical testing performed

• Effect Size: Not applicable — no quantitative effect sizes reported; review is conceptual and narrative in nature

• Primary Outcome: Conceptual demonstration that digital twins — built from multimodal IBD datasets integrating clinical, molecular, imaging and real-world data — could generate synthetic control arms, enable adaptive randomisation, and predict disease relapse or treatment response in IBD clinical trials

• Nnt Or Sensitivity: Not applicable — no NNT, sensitivity, specificity, or hazard ratios reported; early feasibility studies cited from oncology, cardiology and endocrinology are described qualitatively as demonstrating potential to improve statistical power and reduce patient burden without numerical synthesis

• Confidence Interval: Not applicable — no confidence intervals reported

Clinical Application

Currently low for routine implementation. Digital twin technology in IBD requires substantial infrastructure investment including high-quality multimodal data repositories, validated computational models, regulatory-approved validation frameworks, and robust data governance structures. None of these prerequisites are fully established in IBD at present. The technology is more feasible as a research and trial design tool in the medium-to-long term (5–10 year horizon) than as an immediate clinical or trial implementation strategy. Australia has a well-developed IBD research infrastructure through organisations such as the Gastroenterological Society of Australia (GESA) and the Australian IBD Consortium (AIBDC), which maintains prospective cohort data that could theoretically contribute to digital twin training datasets. The Therapeutic Goods Administration (TGA) would need to develop specific guidance on the regulatory acceptance of synthetic control arms generated by digital twins — analogous to evolving FDA and EMA frameworks. The PBS currently funds multiple advanced therapies for IBD (biologics and small molecules including vedolizumab, ustekinumab, infliximab, adalimumab, tofacitinib, upadacitinib, and risankizumab), and digital twin-informed trial design could potentially accelerate access to novel agents by improving trial efficiency. RACGP and GESA guidelines do not currently address digital twin methodology. Australian participation in international IBD trials (e.g., through the ECCO network) positions the country well to contribute to and benefit from digital twin trial innovations, but local regulatory and ethical frameworks will require prospective development. Patients with IBD (Crohn's disease and ulcerative colitis) who are candidates for participation in clinical trials. Potentially applicable to patients with complex, refractory disease where conventional trial recruitment is challenging due to prior biologic exposure, comorbidities, or rare phenotypes. Broader applicability to trial sponsors, regulatory bodies, and clinical research organisations designing next-generation IBD trials.

Abstract

Clinical trials in IBD face difficulties of escalating complexity, high costs and challenges in recruitment. Digital twins are virtual, data-driven replicas of individual patients that model disease trajectories and treatment responses, which offer a potential innovative change in the conduct of clinical trials in IBD. Built from multimodal datasets integrating clinical, molecular, imaging and real-world data, digital twins can generate synthetic control arms, enable adaptive randomisation and predict disease relapse or treatment response. Early studies across oncology, cardiology and endocrinology demonstrate their feasibility and potential to improve statistical power while reducing patient burden. However, the integration of digital twins into clinical trials in IBD will require rigorous validation frameworks, transparent data governance and attention to algorithmic bias and consent. In this review, we explore how digital twins may transform IBD research-from in silico simulation to adaptive, patient-centred trial design-and outline the regulatory, ethical and logistical challenges to be considered in order to successfully integrate them into future trials.

References

1. 1.Colwill, M., Honap, S., Young, A.-M., Magro, F., Jairath, V., Danese, S., & Peyrin-Biroulet, L. (2026). Digital twins in IBD-bridging data, biology and trial innovation. Gut. https://doi.org/10.1136/gutjnl-2026-338447