“Wounds” has just released The Wound Care Collaborative Community’s (WCCC) proposed addendum to the now 20 year old Food and Drug Administration (FDA) Guidance document on chronic wounds. The 2006 FDA guidance predates two decades of scientific progress, so the WCCC has proposed a modernizing addendum. This non-binding, consensus document is intended to spur dialogue among sponsors, investigators, and regulators – not to replace official guidance. There’s a lot to unpack in these suggestions, but I will focus on the ones that I am most passionate about:
- Cross-wound-type data: Because different wound etiologies share overlapping demographics, comorbidities, and healing biology, the authors urge the FDA to consider broader acceptance of clinical data across wound types when strong scientific and clinical justification exists, rather than requiring fully separate evidence for each indication: [While we all understand the fact that “standards of care” may differ from one wound type to another, the idea that the body’s healing mechanism is completely different from one wound type to another and thus necessitates a different trial for every “named wound” is silly, increases the cost of developing novel therapies and limits access for patients. Remember that the LARGEST wound type is the generic “nameless” chronic wound on which there are no trials. CF]
- Study populations: The WCCC’s Natural History Project shows trial populations are persistently narrower and healthier than real-world patients — DFU trials often enroll only low-grade ulcers and exclude common comorbidities, and VLU wound care clinical trials typically cap follow-up around 12 weeks — limiting generalizability. [Stay tuned for much more on the Natural History Project which utilized Intellicure’s real world data repository – the realities of the real world which are well known to every clinician are going to be front and center in upcoming publications from the WCCC! This is why the field needs real world wound care data! CF]
- Endpoints: The FDA still regards complete wound closure as the most meaningful primary endpoint. Alternative endpoints must reflect how patients feel, function, or survive; PAR alone is not clinically meaningful but might work paired with a patient-reported or other clinically meaningful co-primary. The Wound-care Experts/FDA-Clinical Endpoints Project validated 15 patient-centered endpoints. [This one will continue to be a challenge. In 2012, The Alliance of Wound Care Stakeholders published the results of the Panel on Wound Care Evidence-Based Research (POWER™) – “Consensus Principles for Wound Care Research Obtained Using a Delphi Process” establishing a set of principles for wound care research. One ongoing frustration is that the trials on drugs and devices directed at specific barriers to healing – like negative pressure wound therapy – must still report wound closure as an endpoint, rather than an endpoint which measures what they are designed to do! Also, we are going to have to have a lot of discussion around the use of PAR and quality of life which can fail miserably in the real world. CF]
- New elements to consider: Appropriate study length (with recurrence/durability follow-up), optional run-in phases, sound sample-size/power, decentralized trial methods, robust data-analysis plans handling missing data, simplified stratification for small trials, and clearer rules on vehicle/comparator arms.
- Innovative trial designs: Because healing barriers vary even within one wound subtype (infection, poor perfusion, excess inflammation, etc.), the paper recommends biomarker-stratified umbrella trials (multiple targeted therapies in one wound type), basket trials (one therapy across wound types sharing a mechanism), and platform trials (multiple arms under one adaptive master protocol). These points are reinforced by written communication from an FDA/CDER reviewer.
Limitations and conclusion. The authors acknowledge many recommendations lack extensive validation in chronic wound populations and the document doesn’t replace formal FDA guidance. The overall aim is to align regulatory pathways with modern science to accelerate safe, effective wound therapies, with continued regulator–clinician–industry collaboration.
Thank you, Dr. Windy Cole for your tireless leadership coordinating 16 authors!
- Windy Cole, DPM — College of Podiatric Medicine, Kent State University, Kent, OH
- Mitch Sanders, PhD — ProDevLabs, Southborough, MA
- Vickie Driver, DPM — Wound Care Collaborative Community, Malvern, PA
- Marissa Carter, PhD — Strategic Solutions, Inc, Oak Brook, IL
- Peggy Dotson, RN — Wound Care Collaborative Community, Malvern, PA
- Caroline Fife, MD — Intellicure, LLC, The Woodlands, TX
- Sarah Griffiths Langbord, PhD — NOxy Health Products, San Mateo, CA
- Francis James, BFA — TRUE-See, New Orleans, LA
- Holly Korzendorfer, PT, PhD — Marist University, Poughkeepsie, NY
- Maribel Henao, DPM, MSPT — Organogenesis, Canton, MA
- Alisha Oropallo, MD — Northwell Health, New Hyde Park, NY
- Joseph Rolley, MSIA — JTR Business Consulting, LLC, Doylestown, PA
- Robert Snyder, DPM, MSc, MBA — MediWound, Wilmington, DE
- Marjana Tomic-Canic, PhD — Miller School of Medicine, University of Miami, Miami, FL
- Zweli Tunyiswa, BA — Open Wound Research, Puyallup, WA
- Howard Walthall, JD, BSE — Venture Medical, LLC, Missoula, MT
Additional Resources:
If you want to know more about how to use real world data to design a trial, or if you are interested in external controls from a real world repository, contact me! Cfife@intellicure.com
- Consensus principles for wound care research obtained using a Delphi process
- The Impact of Underlying Conditions on Quality-of-Life Measurement Among Patients with Chronic Wounds, as Measured by Utility Values: A Review with an Additional Study – Kristen A. Eckert, Caroline E. Fife, Marissa J. Carter, 2023
- Quality of Life in Patients with Chronic Wounds… and Yes, Our Patients are Very Sick – Caroline Fife M.D.
- PAR for Clinical Decision-Making is Different from PAR for Statistical Inference – Check Out This Blog by Zweli Tunyiswa – Caroline Fife M.D.
Dr. Fife is a world renowned wound care physician dedicated to improving patient outcomes through quality driven care. Please visit my blog at CarolineFifeMD.com and my Youtube channel at https://www.youtube.com/c/carolinefifemd/videos
The opinions, comments, and content expressed or implied in my statements are solely my own and do not necessarily reflect the position or views of Intellicure or any of the boards on which I serve.
