Evidence supporting wound care end points relevant to clinical practice and patients’ lives. Part 2. Literature survey

Abstract

Patients with wounds bear significant clinical, personal, and economic burdens yet complete wound healing is the only United States Food and Drug Administration (FDA) recognized primary clinical trial end point. The overall goal of this project is to work with FDA to expand the list of acceptable primary end points, recognizing that new and innovative treatments, devices, and drugs may not have complete healing as the focus. Part 1 of the project surveyed 628 wound care experts who identified and content‐validated 15 end points most relevant to clinical practice and benefitting patients’ lives as primary outcomes in clinical trials. Part 2 is focused on critical appraisal of the evidence in the wound care literature supporting FDA criteria to qualify these 15 end points as primary end points in clinical trials. Further research involved systematic review of the literature regarding the most promising end points. Forty volunteer, interdisciplinary, wound healing experts in fields related to the end points compiled evidence from systematic MEDLINE searches and society databases supporting the FDA criteria of reliability, clinical construct validity, capacity to detect concurrent or longitudinal change, and responder analysis. The search revealed 485 references involving over 462,000 subjects supporting FDA‐required parameters for all 15 end points More than 50 references supported FDA‐required parameters qualifying the following outcomes for use in clinical trials supporting interventions for FDA clearance: Pain reduction, Physical function and ambulation, Infection reduction, Time to heal, and Percent wound area reduction in 4–8 weeks. Among these, only Time to heal is currently recognized by the FDA as a primary wound outcome in clinical trials. These results suggest that wound science is already serving patients and professionals by improving these content‐validated outcomes that merit regulatory consideration.

Evidence supporting wound care end points relevant to clinical practice and patients' lives. Part 3: The Patient Survey

“…From this published work, 15 wound care endpoints that were rated most relevant (CVI 0.85 or greater) for clinical practice and/or patient benefit were subjected to a rigorous systematic literature review, rating each endpoint based on the FDA criteria for new endpoints, that is, reliability, clinical construct validity, capacity to detect change, and responder analysis. This published literature review found considerable evidence supporting FDA criteria for their suitability as primary endpoints in clinical trials 10 . The results highlight the endpoints that healthcare professionals and educators in the field of wound care believe are relevant to clinical practice or patients' lives.…”

Accelerated Wound Healing in Minipigs by On-Site Production and Delivery of CXCL12 by Transformed Lactic Acid Bacteria

“…Other factors such as exudation, inflammation, and the presence of necrotic tissue or slough may also give an indication on how the healing is progressing [30][31][32]. Thus, extensive efforts have been made to identify appropriate new primary endpoints for wound healing studies [15,16,33]. Even though the primary endpoint of complete healing remains, the FDA recently announced that it is open to discussing new primary endpoints, including (1) Percentage area reduction (PAR), (2) Reduced infection, (3) Reduced pain/reduced analgesia usage, (4) Increased physical function and ambulation, and (5) Quality of life [14].…”

“…Furthermore, additional information collected during monitoring of the healing process forms an untapped resource, which complements the conventional documentation of wound appearance and area [3]. An ongoing collaborative effort with the FDA therefore aims to identify new primary endpoints with improved clinical relevance and patient value [15], and has so far recognized reduced pain, fewer infections, and increased physical function/ambulation as the three most important parameters [16]. Based on these results and the work of the Wound Healing Endpoints Committee led by Driver et al, the FDA recently acknowledged five new endpoints [14].…”

How can we optimize the development of drugs for wound healing?

“…Thus, a collaborative effort (Wound Experts/FDA Clinical Endpoints Project, WEF-CEP) was formed in 2014, with the objective to identify and validate clinically meaningful and patient-centered primary endpoints. As a result, 12 additional endpoints were identified as unmet needs in wound patients [16], and in 2020, the FDA agreed to open up five new primary endpoints for discussion with Sponsors: 1) percent wound area reduction, 2) reduced infection, 3) reduced pain/reduced analgesia use, 4) increased physical function and ambulation, and 5) quality of life together with the evaluation and validation of the instruments for assessment of the above.…”