Paper Information

Diabetic foot ulcers (DFUs) are the leading cause of amputations in people with diabetes, mainly due to poor wound healing. This study evaluated DFU trial designs and analysed observational data from the two prospective Diabetic Foot Consortium (DFC) studies to estimate longitudinal healing and amputation rates, assess the effects of wound surface area and duration on healing, and inform sample size considerations for future trials. We analysed data from Open Wound Master Protocol (MP, n = 419) and c-Myc Biomarker (n = 140). The primary outcome was complete wound healing. Time-to-event analysis estimated healing and amputation rates, with amputations classified as non-healed. Logistic regression assessed the prediction of healing based on baseline wound characteristics, with model performance evaluated using AUC (area under the curve). Sample size calculations were performed to achieve 80% power. In the MP study, healing rates were 26% by week 12% and 49% by week 32; amputation rates were 4% and 10%, respectively. The c-Myc study showed 38% healing and 2.5% amputation by week 12. Wound area and duration significantly predicted healing (AUC ≥ 0.70 by 24 weeks). For smaller treatment effects, predicted healing rates varied by up to 40% between small and large wounds, impacting sample size. Contemporary DFU trial designs and healing times remained largely unchanged over two decades. While shorter trials (e.g., 12 weeks) theoretically require smaller sample sizes due to reduced outcome variance, they risk failing to capture the full treatment effect. Trial design must account for baseline wound characteristics, which should inform eligibility criteria and follow-up.