[show abstract][hide abstract] ABSTRACT: Regulatory requirements for new products should be guided by clinical trials that protect the public by a thorough evaluation of safety and efficacy, while not creating unnecessary barriers to their development and ultimate approval. While healing a wound is the ultimate goal of treating an individual with a diabetic foot ulcer, achieving this goal is physiologically complex requiring the initiation and interaction of many events and therefore unlikely to be achieved by one compound. We believe that developing new, more meaningful, study outcomes or end points in wound care trials would both aid in determining the true efficacy of wound management modalities and facilitate the product development cycle. The primary guidance from the US Food and Drug Administration to industry in this field was published in 2006. This document, while helpful and largely in concert with current knowledge of wound healing, needs to be substantially improved. We therefore convened an interdisciplinary task force comprising experts in various aspects of wound care to attempt to achieve consensus in defining primary outcomes and potential secondary endpoints for various classes of wound-healing modalities.
International Wound Journal 07/2009; 6(3):211-3. · 1.60 Impact Factor
[show abstract][hide abstract] ABSTRACT: The purpose of this manuscript was to determine whether the change in wound surface area over time could be described through nonlinear mathematics.
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.
[show abstract][hide abstract] ABSTRACT: Wound geometry measurements have long been associated with wound-healing outcomes but there is little published evidence to support this. We studied serial wound tracings of 338 venous leg ulcers (VLUs) that had been followed during a controlled, prospective, randomized pivotal trial of two topical wound treatments, to determine whether the relationship between wound surface area and wound perimeter planimetry measurements, as well as the qualitative assessment of wound shape, could be correlated to wound-healing outcomes. VLUs that transitioned to a more convex wound shape, and maintained a linear relationship between their wound margin size and wound surface area size, had faster healing rates and were more likely to completely heal by 12 weeks (odds ratio=4.84, p=0.001). VLUs that initially presented with isolated areas of epithelium within the wound margins, large concavities, or were segmented into multiple ulcers typically had a poorer linear correlation between their margins and their surface area. Only 18 out of 134 (13%) VLUs with a linear r(2)<0.80 eventually reached full wound closure, vs. 43% (102 of 270) of the remaining wounds with an r(2)> or =0.80 (Fisher's exact p<0.001). We believe our results show that the proportional relationship between one-dimensional perimeter and area measurements accurately correlates to the healing progress of the wound. Wounds that do not correlate to this linear relationship (concave geometries or multiple islands of healing) may be physiologically different than wounds that have good linear correlation, which we concluded through the analysis of wound acetate tracings.
Wound Repair and Regeneration 01/2009; 17(2):173-8. · 2.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: This investigation was conducted to determine if a correlation exists between wound healing outcomes and serial debridement in chronic venous leg ulcers (VLUs) and diabetic foot ulcers (DFUs). We retrospectively analyzed the results from two controlled, prospective, randomized pivotal trials of topical wound treatments on 366 VLUs and 310 DFUs over 12 weeks. Weekly wound surface area changes following debridement and 12-week wound closure rates between centers and patients were evaluated. VLUs had a significantly higher median wound surface area reduction following clinical visits with surgical debridement as compared with clinical visits with no surgical debridement (34%, p=0.019). Centers where patients were debrided more frequently were associated with higher rates of wound closure in both clinical studies (p=0.007 VLU, p=0.015 DFU). Debridement frequency per patient was not statistically correlated to higher rates of wound closure; however, there was some minor evidence of a positive benefit of serial debridement in DFUs (odds ratio-2.35, p=0.069). Our results suggest that frequent debridement of DFUs and VLUs may increase wound healing rates and rates of closure, though there is not enough evidence to definitively conclude a significant effect. Future clinical research in wound care should focus on the relationship between serial surgical wound debridement and improved wound healing outcomes as demonstrated in this study.
Wound Repair and Regeneration 01/2009; 17(3):306-11. · 2.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study was undertaken to determine if healing rates are reliable early predictors of ultimate complete wound closure in venous leg ulcers and diabetic foot wounds. We conducted a retrospective analysis of 306 venous leg ulcers and 241 diabetic foot ulcers enrolled in two large controlled, prospective, randomized pivotal trials to compare topical wound treatments, to determine whether certain early markers of healing could be correlated with later total wound closure. Two-sided tests at 95% confidence demonstrated that wound margin advance, initial healing rate, percent wound surface area reduction, and wound healing trajectories (all p<0.001) were powerful predictors of complete wound healing at 12 weeks. Wounds with poor healing progress by these criteria at 4 weeks were highly likely to remain unhealed after 8 additional weeks of treatment. Analysis of the diabetic foot ulcers and venous leg ulcers subgroups separately demonstrated consistent statistical test results with high significance; similarly, the results remained valid independent of the topical treatment used. The early prediction of eventual wound healing or nonhealing using early healing rates may enable more efficient triage of patients to advanced healing technologies. We believe that these surrogate markers are robust predictors of healing regardless of wound etiology and that they merit wider use in clinical trials and routine patient care.
Wound Repair and Regeneration 01/2008; 16(1):19-22. · 2.76 Impact Factor