Patient-centred and fit-for-purpose clinical trials in rare cancers: lessons from sarcomas for operationalising 2024 WHO Guidance and ICH E6(R3)

Abstract

Rare cancers account for approximately one quarter of cancer diagnoses in Europe, yet prevailing clinical trial governance frameworks were developed for common malignancies and conventional randomised designs. The 2024 WHO Guidance for best practices for clinical trials and ICH E6(R3) reframe trial quality around scientific validity, ethical proportionality, feasibility, equity, and meaningful patient engagement — principles that are structurally tested by rare cancer research. This narrative review examines how these principles are operationalised in representative sarcoma trials, where biological heterogeneity, low incidence, and international collaboration expose the limits of standard approaches. Drawing on examples from Bayesian designs, umbrella and platform trials, registry-based approaches, decentralised participation, and structured advocacy involvement, we identify recurring governance features associated with successful implementation in rare cancer settings. Patient-centred approaches — particularly early integration of patient-reported outcomes (PROs), risk-proportional oversight, and attention to participant burden — emerge as key determinants of feasibility, recruitment, retention, and interpretability. In rare cancers, patient-centred, fit-for-purpose governance is not an ethical adjunct but a structural determinant of operational validity. Lessons from sarcoma trials can be extended beyond rare cancers to molecularly stratified subsets of common malignancies. Funding This work received no specific funding from public, commercial, or not-for-profit organisations.