Nonlinear modeling of venous leg ulcer healing rates

We studied 3,588 serial wound tracings of 338 venous leg ulcers (VLUs) that had been followed during a controlled, prospective, randomized trial of two topical wound treatments.A majority (72%) of VLUs exhibited surface area reduction via an exponential decay model, particularly during the early stages of healing. These results were consistent with the mechanics of wound contraction and epithelial cell proliferation, supported by the higher frequency at which exponential surface area reduction associated with full wound closure (35% of wounds that fit the exponential model healed vs. 21% of wounds that did not fit the exponential model completely healed during the study period, p = 0.018). Goodness-of-fit statistics suggested that much of the individual variation in healing could be described as nonlinear variation from the exponential model.We believe that parameter estimates from a mathematical model may provide a more accurate quantification of wound healing rates, and that similar models may someday reach routine use in comparing the efficacy of various treatments in routine practice and in product registration trials.While sophisticated mathematical analyses have been used to model the kinetics of wound closure, such models have not reached widespread acceptance among clinicians or regulatory authorities. Healing rates continue to be most widely reported as percent surface area reduction over time, and registration trials typically use a binomial outcome (i.e. completely healed vs. not completely healed on a chosen day) to judge product efficacy. Many clinicians realize that such an approach is problematic, and that such analysis fails to describe adequately to what extent a wound has healed in response to its treatment regimen. In addition, a reliable model that would enable one to predict chance of healing and to project the time to complete healing would be useful in the clinical arena. Quantitating intermediate degrees of healing is critical in order to dec