Is Complete Wound Healing a Valid Endpoint for Clinical Trials of Venous Stasis Ulcer Treatment?

Abstract

Complete wound healing is often used as an endpoint in clinical trials comparing different treatments of venous stasis ulcers. The authors have found, however, that determining exactly when a wound is completely healed is often difficult and quite subjective. Because of this concern, they undertook the following survey.

Photographs of 46 venous stasis ulcers were classified by the authors as obviously healed (H, n=5), obviously not healed (NH, n=7), and ambiguous (Amb, n=34). Blinded reviewers were instructed to judge the wounds as if they were conducting a clinical trial, and were asked: (1) Is the wound healed? (yes/no/can't tell), and (2) If forced to decide yes or no for question 1, which would you choose? (yes/no).

Forty-eight reviewers took part in the study: 29 physicians or nurse clinicians with a specialty in wound care (MD/RN) and 19 medical students (MS). When given the three options, they classified 17% of the wounds as "can't tell" (H 27%, NH 5%, Amb 17%). The percentage of reviewers disagreeing with the majority opinion was determined for each wound, when the reviewers were forced to choose either "healed" or "not healed." (The least amount of consensus would be 50% disagreement, with the reviewers split 50/50 on the classification. The greatest consensus would be 0% disagreement, with all reviewers agreeing.) The overall percentage of disagreement was 24%. The percentage of disagreement on Amb wounds was 29%, for H wounds 18%, and for NH wounds 7%. The results were similar when reviewed by MD/RN (Amb 25%, H 9%, NH 4%) or MS (Amb 27%, H 30%, NH 10%). There was >90% consensus for only 3% of Amb wounds (MD/RN 9%, MS 3%).

The precise determination of complete wound healing is quite subjective and variable, even among observers with great experience in wound care. There is great potential to introduce bias into clinical trials that employ complete wound healing as an endpoint. It should, therefore, be used only with great caution.