The regulatory landscape for wound care therapeutics has long lagged behind scientific progress. The FDA’s existing guidance document for chronic cutaneous ulcer and burn wounds, originally released in 2006, has not kept pace with the explosion of knowledge in wound pathophysiology, diagnostic tools, and therapeutic technologies.¹ In response, the Wound Care Collaborative Community (WCCC) spearheaded a multistakeholder initiative to modernize clinical trial recommendations for chronic wounds. The goal of this effort is to align regulatory expectations with contemporary science and clinical practice, ultimately supporting more relevant product development and better patient outcomes. The process of creating these recommendations was outlined in a poster presented at the Symposium on Advanced Wound Care Fall 2025 in Las Vegas, Nevada.

A multidisciplinary WCCC task force undertook a comprehensive review of the current literature, incorporating 35 newly evaluated references to inform updated recommendations.¹ The task force focused on both preclinical and clinical trial considerations, emphasizing the need to integrate validated scientific methods and realistic clinical conditions into trial design.¹ The resulting proposals are intended to serve as an addendum to the current FDA guidance and include detailed docket comments submitted to the FDA, as well as a comprehensive manuscript to be submitted to a peer-publication.¹

One of the major emphases of the proposed updates is the need for better preclinical modeling. Current animal models often fail to simulate human wound healing accurately.¹ The WCCC calls for standardized model selection and reporting, noting that biological variables such as species, age, and sex can significantly influence outcomes.¹ In particular, the authors recommend combining models to better replicate the complexities of chronic wounds in human populations.¹ Bioassays, the WCCC says, should be aligned with a product’s specific mechanism of action and designed to measure relevant biological processes like angiogenesis or epithelialization.¹

The proposed guidance also suggests several enhancements to clinical trial design. Recommendations include ensuring that study duration and run-in phases reflect realistic healing timelines and that recruitment strategies, such as decentralized trials, are adopted to improve participation.¹ The task force underscores the need for balance in sample size planning; trials must maintain statistical power while remaining feasible.¹ Importantly, trial populations should reflect the real-world patient populations most affected by chronic wounds, which are often underrepresented in randomized controlled trials.¹

In terms of wound assessment, the WCCC encourages the adoption of objective, reproducible measurement tools. The use of standardized photographic documentation and digital devices capable of calculating metrics like Percent Area Reduction (PAR) and Percent Volume Reduction (PVR) is recommended.¹ These tools are intended to reduce subjectivity in endpoint assessment and improve data reliability. In addition, the guidance calls for improved ulcer classification systems, recommending the integration of the NPIAP and Wagner grading systems to facilitate consistency across studies.1

The task force also explored the potential of emerging diagnostic technologies. These include tissue biopsies and autofluorescence imaging for identifying biofilms, as well as biomarkers that may predict healing or guide therapy.¹ Although no biomarkers have yet been FDA-approved, their inclusion in trials could offer insight into wound status and trajectory.¹ The discussion further highlights the roles of tissue pH, proteases, and oxygenation levels in wound progression—factors that may one day serve as early indicators of therapeutic response.¹

Finally, the authors stress the importance of using clinically meaningful and patient-centered endpoints. In addition to standard metrics like time to wound closure and area/volume reduction, outcomes such as infection reduction, pain relief, improved mobility, and reduced rates of recurrence or amputation are proposed as key indicators of therapeutic success.¹ The inclusion of these endpoints signals a shift toward trials that more accurately reflect the priorities of both clinicians and patients.

The WCCC’s recommendations represent a much-needed effort to modernize the regulatory framework surrounding chronic wound therapies. By incorporating current scientific understanding, advocating for methodological rigor, and emphasizing patient-centered care, this initiative provides a timely roadmap for improving how wound products are tested and approved. If adopted, these updates could reshape clinical research in wound care, bringing it closer to the realities of bedside practice and, ultimately, improving healing outcomes for patients.

Reference:

1.        Cole W, Sanders M, Driver V, et al. Wound Care Collaborative Community Recommendations for Chronic Wounds: FDA Guidance Update on Clinical Trial Design. Presented at the Symposium on Advanced Wound Care Fall 2025, Las Vegas, NV.