Surrogate end points for the treatment of diabetic neuropathic foot ulcers.
OBJECTIVE
The goal of this study was to determine whether surrogate markers based primarily on changes in the size of a wound can be used to correctly predict which individuals with diabetic neuropathic foot ulcers will heal after 12 or 20 weeks of care.


METHODS
This is a retrospective cohort study using the Curative Health Services database. As many as 39,918 neuropathic wounds on 20,213 individuals with diabetes were evaluated. Seven surrogates based on changes in wound size were evaluated.


RESULTS
Surrogates measured after 2, 4, or 8 weeks of care and based on percentage change in area, log healing rate, and log area ratio discriminated well with respect to differentiating between those wounds that healed and those that did not heal by the 12th or 20th week of care. For example, after 4 weeks of care, the percentage change in area can be used to correctly discriminate 76% of the time between those that healed and those that did not by the 20th week of care.


CONCLUSIONS
The surrogate markers can be used in clinical trials such that shorter and smaller trials can be conducted with reasonable accuracy in order to determine which potential new therapeutics should be studied in larger, longer trials. In addition, the surrogates may also benefit clinicians when they are trying to decide whether a wound care therapy will ultimately be successful.
Margolis
David J
DJ
Department of Dermatology and Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. dmargoli@cceb.med.upenn.edu
Gelfand
Joel M
JM
Hoffstad
Ole
O
Berlin
Jesse A
JA
D000368:Aged; D000465:Algorithms; D003646:Debridement; D003929:Diabetic Neuropathies / Q000628:therapy*; D016523:Foot Ulcer / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D008875:Middle Aged; D011237:Predictive Value of Tests; D012372:ROC Curve; D013997:Time Factors; D016896:Treatment Outcome; D014945:Wound Healing