Borrowing from the cancer playbook: a master protocol basket trial for hard-to-heal wound therapeutics targeting shared pathobiology.
Hard-to-heal wounds, such as diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs), remain associated with poor healing outcomes despite optimised standard care. Although classified by aetiology, these wounds share common pathophysiological features that may be amenable to mechanism-targeted therapies. This manuscript aims to describe the design, scientific rationale and statistical framework of a mechanism-driven basket trial evaluating wound therapies across multiple wound aetiologies.
This multicentre, randomised, sham-controlled clinical trial was designed under a master protocol using aetiology-specific baskets. Adults with hard-to-heal DFUs or VLUs who failed to demonstrate adequate healing during a standardised run-in period were randomised 1:1 within each basket to standard care plus active therapy or standard care plus sham. Subject and assessor blinding, harmonised standards of care, and centralised endpoint adjudication were employed. The primary endpoint within each basket was complete wound closure by 12 weeks, confirmed at two consecutive visits. Bayesian statistical methods incorporating conservatively discounted historical control data via power priors were used to enhance efficiency while preserving indication-specific inference.
The basket design enabled simultaneous evaluation of a single mechanism-targeted intervention across heterogeneous wound aetiologies while maintaining methodological rigour, regulatory alignment and interpretability. Independent analysis of each basket preserved aetiology-specific conclusions while benefiting from shared infrastructure and standardised procedures.
This master-protocol basket trial adapted principles established in oncology to wound care, offering an innovative and scalable framework for evaluating therapies targeting shared biological barriers to healing. The approach may accelerate evidence generation and inform future clinical development strategies in hard-to-heal wounds.
This multicentre, randomised, sham-controlled clinical trial was designed under a master protocol using aetiology-specific baskets. Adults with hard-to-heal DFUs or VLUs who failed to demonstrate adequate healing during a standardised run-in period were randomised 1:1 within each basket to standard care plus active therapy or standard care plus sham. Subject and assessor blinding, harmonised standards of care, and centralised endpoint adjudication were employed. The primary endpoint within each basket was complete wound closure by 12 weeks, confirmed at two consecutive visits. Bayesian statistical methods incorporating conservatively discounted historical control data via power priors were used to enhance efficiency while preserving indication-specific inference.
The basket design enabled simultaneous evaluation of a single mechanism-targeted intervention across heterogeneous wound aetiologies while maintaining methodological rigour, regulatory alignment and interpretability. Independent analysis of each basket preserved aetiology-specific conclusions while benefiting from shared infrastructure and standardised procedures.
This master-protocol basket trial adapted principles established in oncology to wound care, offering an innovative and scalable framework for evaluating therapies targeting shared biological barriers to healing. The approach may accelerate evidence generation and inform future clinical development strategies in hard-to-heal wounds.