Percentage area reduction at week 4 as a prognostic indicator of complete healing in patients treated with standard of care: a post hoc analysis

Abstract:

Early indicators of healing provide valuable information on the potential benefit of treatment. In patients with hard-to-heal (chronic) diabetic foot ulcers (DFUs), timely intervention is critical. Ulcers that fail to show measurable progress within four weeks of treatment are considered recalcitrant. These ulcers increase the risk of soft tissue infection, osteomyelitis and lower extremity amputation. A prognostic indicator or surrogate marker allows for rapid evaluation of treatment efficacy and safety. An inverse correlation between a percentage area reduction (PAR) of ≤50% at week 4 and complete healing by week 12 has been previously established; however, the data were derived from a standard of care (SoC) arm of clinical trials that are over a decade old. In this post hoc analysis, data from a large multicentre prospective randomised controlled trial were reviewed to assess PAR at week 4 as a prognostic indicator in patients treated with SoC. Overall, 65.4% (17/26) of patients with PAR >50% at week 4 achieved complete closure at week 12. The receiver operating characteristic (ROC) curve for area reduction by week 4 showed strong discrimination for predicting non-healing (area under the ROC curve: 0.92; p<0.001; positive predictive value: 70.6%; negative predictive value: 87.2%). These findings are consistent with previous studies and support the use of four-week PAR as a prognostic indicator.

Conclusion:

The results of this post hoc analysis confirm previous reports that four-week PAR is a valid surrogate endpoint, predicting healing at 12 weeks. It allows clinicians to discriminate between ulcers that are likely to heal and those that require more advanced therapy. The surrogate endpoint is important in clinical trial design for FDA approval of wound care products. Its use has been recommended by the 2006 FDA guidance document, using an early ‘run in’ period as an early screening tool to identify rapidly healing wounds.24 Ample research has demonstrated its broader potential to inform clinical practice and improve patient outcomes.

Citation:

Serena T, Sadia Y, Yaakov R, et al. Percentage area reduction at week 4 as a prognostic indicator of complete healing in patients treated with standard of care: a post hoc analysis. Journal of Wound Care. 2024 Sep 1; 33(9): S36-42. doi: 10.12968/jowc.2024.0141