J Wound Care. 2026 Jan 2;35(1):35-46. doi: 10.12968/jowc.2025.0609. Epub 2025 Dec 19.
ABSTRACT
OBJECTIVE: Cellular, acellular, and matrix-like products (CAMPs) are widely used for treating hard-to-heal lower-extremity diabetic ulcers (LEDUs) and venous leg ulcers (VLUs); yet, limited evidence exists to demonstrate that clinical outcomes differ across the US Food and Drug Administration's (FDA) regulatory categories: section 361 products; 510(k) devices; and premarket approval products. Despite substantial differences in evidentiary requirements, the FDA's regulatory categories largely distinguish CAMPs by their origin, degree of manipulation and intended purpose, rather than by demonstrated comparative effectiveness. The Centers for Medicare and Medicaid Services' (CMS) commissioned technology assessments and systematic reviews similarly report insufficient evidence that any specific CAMP category consistently outperforms another. Prospective randomised 'controlled' trials rarely include the complex, multimorbid populations seen in routine practice and 'real-world' data, whether collected prospectively or retrospectively. Yet routine practice and real-world data are essential for understanding how these technologies perform in actual Medicare beneficiaries. This study evaluated whether regulatory classification predicts real-world clinical effectiveness and how CAMP-treated episodes compare with standard of care (SoC) alone.
METHOD: To address this evidence gap, a retrospective cohort study using 2.65 million LEDU and 745,411 VLU episodes from the CMS 100% Limited Data Set (2016-2024) was conducted. Episodes receiving CAMPs were stratified by FDA regulatory categories, and four-way 1:1 matching was applied to balance cohorts across age, comorbidities, episode year, time to treatment and debridement depth. Outcomes included episode length of treatment (LoT), CAMP LoT, amputations, infections, mortality and hospital utilisation. Multiple comparisons were controlled using Bonferroni-adjusted alpha thresholds.
RESULTS: Across matched cohorts (n=3585 LEDUs and n=2492 VLUs episodes per group), differences in outcomes between CAMP regulatory pathways were minimal. In contrast, all CAMP categories significantly outperformed standard of care (SoC) alone. CAMP-treated episodes demonstrated lower mortality, fewer major amputations, and substantially reduced inpatient, emergency department, intensive care unit and coronary care unit use compared with SoC-alone episodes. These benefits were consistent across wound sizes (<20cm2 and ≥20cm2), and across both LEDU and VLU aetiologies, with only two VLU exceptions: overall episode LoT and minor amputation rates, which did not differ significantly from SoC after adjustment for multiple comparisons. Although CAMP LoT varied modestly across regulatory categories, these differences did not translate into meaningful differences in clinical outcomes. SoC-alone episodes exhibited slightly shorter episode LoT but at the expense of markedly higher complications and healthcare utilisation.
CONCLUSION: In Medicare beneficiaries with hard-to-heal wounds, the regulatory pathway or category does not meaningfully predict real-world clinical effectiveness. CAMP therapy plus SoC, regardless of regulatory classification, consistently improves outcomes compared with SoC alone, reducing complications and hospital utilisation across wound sizes and aetiologies. These findings indicate that tiered reimbursement frameworks based on FDA regulatory categories lack empirical justification. Payment policy should instead prioritise demonstrated improvements in patient-centred outcomes, including reductions in amputations, infections, hospitalisations, and total Medicare spending. The evidence supports outcome-based rather than regulatory category-based reimbursement for CAMPs and reinforces the importance of timely CAMP initiation (≈30 days) along with consistent application following parameters for use.
PMID:41528785 | DOI:10.12968/jowc.2025.0609