A new initiative supported by both the Association for the Advancement of Wound Care (AAWC) and the Wound Healing Society (WHS)—the “Wound Care Expert/FDA-Clinical Endpoint Project” (WEF-CEP)—will take an updated list of primary endpoints for wound care trials to the US Food and Drug Administration (FDA), as revealed at the Symposium of Advanced Wound Care Fall meeting (SAWC Fall 2019; 12–14 October, Las Vegas, USA).
Vickie Driver (Brown University School of Medicine, Providence, USA), one of many clinicians who volunteered as part of the project, began: “Five years ago we approached the FDA, because we realised that in the field of wound care, the only endpoint which is recognised in clinical practice or a clinical trial is complete wound closure.”
“As a clinician, I am judged based on whether or not I close a patient’s wound. I would like to be judged on how well I am practicing medicine and preventing amputations, but we have become very siloed into thinking we should close every wound tomorrow.”
Due to the limitations that current regulations impose on the development of new medicine and therapies for wound healing, especially for patients with a myriad of other complications, the WEF-CEP project was launched. According to Driver, the FDA stipulated that additional endpoints would have to be planned, presented and evaluated using “FDA qualified criteria” for new clinical outcomes. As a result, Driver et al were required to analyse data with a four-point Likert response format, as well as considering factors such as reliability, clinical construct validity and capacity to detect change.
Following advice from the FDA, researchers with the WEF-CEP project conducted a survey of 628 clinicians and researchers, including members of both the AAWC and WHS, over four different time periods between January 2015 and October 2015. “This is the list of the top endpoints that were important to clinicians for clinical practice and what matters to them every single day when treating patients,” said Driver, explaining the findings of the survey.
The list, which was divided into clinical practice and patient-centred outcomes, ranged from percentage area reduction (PAR) reduction in four to eight weeks—described by Driver as an important “predictor of complete closure”—to amputation reduction. Other top endpoints included the reduction of infection, bioburden, recurrence and pain, as well as social factors such as social isolation and depression.
Following the collection of data, the next step was to analyse this information and research the relevant literature. Driver said: “We created four teams of physical therapists, podiatrists, wound care doctors and nurses. We also had a huge team of 40 researches across the USA that entered into one of these teams based on their experience and evaluated the evidence based on FDA regulations.”
Based on the 146 papers that fulfilled FDA requirements and were reviewed, supportive pain was revealed to be an important endpoint in wound healing, as well as time to heal, physical function/ambulation and, once again, amputation reduction. All of these endpoints were looked at as they related to the data, before an IRB-approved survey of patients was conducted, receiving 451 responses from over 26 states.
Turning her focus to the results of this survey, Driver commented: “What is interesting here is the age of these patients. We are obligated to these patients for 20–40 years once they have a wound: it is not the end of their life. For this reason, it is critical that we develop public policy that actually supports and allows us to get payment for therapies that matter, so they are covered and we do not have to put the burden on the patient to pay for these things.”
Summarising the key points of the WEF-CEP project, Driver concluded: “What I want to point out here is that endpoints which mattered to clinicians and the industry also mattered to patients. Fortunately, we are all on the same page, but this had to be done to prove that: not only for the FDA, but for us. This is the final list of primary endpoints that we will take to the FDA that have tools to measure them, because if you add endpoints, there has way to measure them that the FDA and CMS agrees with.”