Standardizing Clinical Trial Endpoints in Wound Healing Protection Status
standardizing clinical trial endpoint

by Thomas E. Serena MD, FACS, FACHM, FAPWCA

Recently, I had the pleasure of attending Puccini's opera Turandot at New York's Metropolitan Opera House. In my favorite scene, young prince Calef comes upon a gruesome tableau: Potential suiters for the princess Turnadot must answer three questions correctly in order to win her hand. On the downside, one incorrect answer is rewarded with a beheading. Calef takes the challenge and answers all three questions flawlessly. Yet, the princess begs her father not to force her to marry the stranger. Calef intercedes saying that if she can guess his name before dawn he will release her from her obligation. Confident of conquest, he sings Nessun dorma (none shall sleep), the opera's most famous aria.

Endpoints: Wound Closure and Quality of Life

The parallels between Italian Opera and the field of wound healing are endless. If only investigators in our space would attend more operatic performances! I would advocate CME for Puccini and Verdi. Puccini understood clinical trial endpoints: one wrong answer and it's "off with your head." In order to obtain the answers to the innumerable questions in our world of wound care we must all use the same validated clinical trial endpoints. The validated endpoints currently available include:

  • Complete closure of the wound at 12 weeks.
  • Surrogate endpoints: 40% closure of venous leg ulcers at 4 weeks and 50% closure of diabetic foot ulcers at 4 weeks.
  • Improvement in patient quality of life.

However, recently an article appeared in Diabetes Care, "Hyperbaric Oxygen Therapy Does Not Reduce Indications for Amputation in Patients With Diabetes With Non healing Ulcers of the Lower Limb: A Prospective, Double-Blind, Randomized Controlled Clinical Trial."

The authors clearly have never seen an opera.

The endpoint they employed: send a picture to a single vascular surgeon and ask him if he would amputate the patient's leg based on the photo. They concluded that hyperbaric oxygen therapy did not prevent amputations. You might ask what happened to the patients who were photographically amputated? Many of them went on to complete wound closure. In contrast, a recent article from Europe determined that a vast majority of patients with diabetic foot ulcers do not require amputation either minor or major. This article suggested that we are too quick to ply the surgeon's trade.

In short, photographic amputation is not a valid clinical trial endpoint and is not supported by the literature.

Initiating Standardized Clinical Trial Endpoints in Wound Care

We cannot simply make up our own endpoints – what should have been amputated in the example above was the person's head who thought this was a good idea! If only Puccini were still alive. The Association for the Advancement of Wound Care (AAWC) under the leadership of current president Vickie Driver has undertaken an initiative along with the FDA to clearly define and standardize clinical trial endpoints in wound healing. I applaud the AAWC and as President-elect, I look forward to continuing this important effort. Clinical trials in wound and hyperbaric medicine are too precious to throw away because we as a group have not standardized our endpoints.

Calef's fabulous aria ends with vincero (victory). I hope through the efforts of clinical investigators across the globe we settle on clear-cut endpoints in wound healing. Perhaps then, we can be spared the silliness and the peril of trials with invented endpoints.

About The Author
Dr. Thomas Serena has published more than 75 peer-reviewed papers and has made in excess of 200 presentations worldwide. He has been elected to the Board of Directors of both The Wound Healing Society and the American College of Hyperbaric Medicine (ACHM), the leading academic society in the field of Hyperbaric Medicine. In 2014 Dr. Serena was elected president of the American Professional Wound Care Association (APWCA). Dr. Serena has opened and operates Wound Care and hyperbaric oxygen treatment clinics across the United States.

The views and opinions expressed in this blog are solely those of the author, and do not represent the views of WoundSource, Kestrel Health Information, Inc., its affiliates, or subsidiary companies.


I do not have a problem with the endpoint used in this study. Although it was not the one I would have chosen, it was fair across all groups. The bigger problem was that the generous inclusion criteria meant that the patients chosen for the study were not necessarily good candidates for hyperbaric therapy. Because most of the patients did not have a non-healing wound due to low oxygenation, they diluted the results of the patients who required additional oxygen for their wounds to remain uninfected and close.

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