Real-World Evidence Complements Randomized Controlled Trial Data in Complex Wound Care: Early Experience with Three-Dimensional Acellular Wound Matrix (3D-ACM) in a Clinical Registry
Main Article Content
Abstract
Introduction: Randomized controlled trials (RCT) and real-world evidence represent complementary approaches in clinical research, each with distinct strengths and limitations. Randomized controlled trials (RCT) are regarded as the gold standard for establishing efficacy because of their rigorous design and control over variables, but they are often criticized for limited generalizability to broader patient populations. In contrast, real-world evidence (RWE), derived from routine clinical practice, captures outcomes across diverse, heterogeneous populations and settings, enhancing applicability to clinical decision-making.
Discussion: This manuscript reviews the advantages and limitations of both methodologies, emphasizing their complementary roles in generating robust evidence. RCTs offer strong internal validity through randomization, blinding, and strict eligibility criteria, while RWE provides external validity by reflecting patient diversity, long-term outcomes, and care patterns in everyday practice.
Conclusion: Early clinical experience with a three-dimensional acellular wound matrix illustrates how registry-derived RWE can complement ongoing RCTs in wound care. This dual evidence strategy underscores the importance of aligning trial rigor with real-world complexity to generate clinically relevant, patient-centered data that further supports innovation, regulatory pathways, and reimbursement frameworks.
Keywords:
Evidence-Based Practice, Randomized Controlled Trials, Diabetic Foot, Tissue Scaffolds, Wound Healing, Skin Ulcer
Article Details
How to Cite
SNYDER, Robert J.; ROLLEY, Joseph.
Real-World Evidence Complements Randomized Controlled Trial Data in Complex Wound Care: Early Experience with Three-Dimensional Acellular Wound Matrix (3D-ACM) in a Clinical Registry.
Medical Research Archives, [S.l.], v. 13, n. 12, dec. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/7127>. Date accessed: 02 jan. 2026.
doi: https://doi.org/10.18103/mra.v13i12.7127.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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29. Reprise data on file.
30. Chaffin AE, et al. Cellular, acellular and matrix-like products (CAMPs) for soft-tissue reconstruction. J Wound Care. 2025;34(Suppl B):S2-S20.
31. Abdo RJ, Couch AL. Use of three-dimensional acellular collagen matrix in deep or tunneling diabetic foot ulcers: a retrospective case series. J Wound Care (North Am Suppl). 2024;33(9):1-6.
32. Snyder RJ, Cardinal M, Dauphinee D, Stavosky J. A post-hoc analysis of reduction in diabetic foot ulcer size at 4 weeks as a predictor of healing by 12 weeks. Wound Manag Prev. 2010;56(3):44-48.
33. Warriner RA, Snyder RJ, Cardinal MH. Differentiating diabetic foot ulcers that are unlikely to heal by 12 weeks following achieving 50% percent area reduction at 4 weeks. Int Wound J. 2011;8:632-637.
34. Sheehan P, Jones P, Caselli A, Giurini JM, Veves A. Percent change in wound area of diabetic foot ulcers over a 4-week period is a robust predictor of complete healing in a 12-week prospective trial. Diabetes Care. 2003;26(6):1879-1882.
35. Margolis DJ, Berlin JA, Strom BL. Which randomized controlled trials in wound care are applicable to your patient? Estimating the applicability of wound care randomized controlled trials to general wound-care populations. Wound Repair Regen. 2003;11(6):387-392.
2. Friedman LM, Furberg CD, DeMets DL, Reboussin DM, Granger CB. Fundamentals of Clinical Trials. 5th ed. New York: Springer; 2015.
3. Van Spall HGC, Toren A, Kiss A, Fowler RA. Eligibility criteria of randomized controlled trials published in high-impact general medical journals: a systematic sampling review. JAMA. 2007;297 (11):1233-40. doi:10.1001/jama.297.11.1233
4. U.S. Food and Drug Administration. Framework for FDA’s Real-World Evidence Program. Silver Spring, MD: FDA; 2018. Available from: https://www.fda.gov/media/120060/download
5. Sherman RE, Anderson SA, Dal Pan GJ, Gray GW, Gross T, Hunter NL, et al. Real-world evidence — what is it and what can it tell us? N Engl J Med. 2016;375(23):2293-7. doi:10.1056/NEJMsb1609216
6. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329(14): 977-86. doi:10.1056/NEJM199309303291401
7. Willy C, Agarwal A, Andersen CA, et al. Closed incision negative pressure therapy: international multidisciplinary consensus recommendations. Int Wound J. 2017;14(2):385-98. doi:10.1111/iwj.12612
8. U.S. Food and Drug Administration. Advancing Health Through Innovation: New Drug Therapy Approvals 2020. Silver Spring, MD: FDA; 2021. Available from: https://www.fda.gov/media/145616/download
9. Tufts Center for the Study of Drug Development. The cost of developing a new drug. Available at: https://csdd.tufts.edu. Accessed October 2023.
10. Wang SV, Schneeweiss S, Berger ML, et al. Reporting to improve reproducibility and facilitate validity assessment for healthcare database studies: a joint ISPOR-ISPE special task force report. Value in Health. 2017;20(8):1009-1022. doi:10.1016/j.jval.2017.08.3018.
11. U.S. Food and Drug Administration (FDA). Examples of Real-World Evidence (RWE) Used in Medical Device Regulatory Decisions. Silver Spring, MD: CDRH; 2021.
12. Centers for Medicare & Medicaid Services (CMS). Decision Memo for Transcatheter Aortic Valve Replacement (TAVR) (CAG-00430R). Baltimore, MD: CMS; March 26, 2019. Available at: https://www.cms.gov/medicare-coverage-database/view/ncacal-decision-memo.aspx?proposed=N&NCAId=293 . Accessed August 11, 2025.
13. Centers for Medicare & Medicaid Services (CMS). Decision Memo for Screening for Lung Cancer with Low Dose Computed Tomography (LDCT) (CAG-00439R). February 10, 2022. Available at: https://www.cms.gov/medicare-coverage-database/view/ncacal-decision-memo.aspx?proposed=N&NCAId=304. Accessed August 11, 2025.
14. Palmetto GBA. MolDX: Pigmented Lesion Assay. Local Coverage Determination (LCD): L38151. Centers for Medicare & Medicaid Services; 2020. Available from: https://www.cms.gov/medicare-coverage-database.
15. Sherman RE, Anderson SA, Dal Pan GJ, Gray GW, Gross T, Hunter NL, LaVange L, Marinac-Dabic D, Marks PW, Robb MA, Shuren J, Temple R, Woodcock J, Yue LQ, Califf RM. Real-world evidence — what is it and what can it tell us? N Engl J Med. 2016;375(23):2293–2297. doi:10.1056/ NEJMsb1609216.
16. Fife CE, Eckert KA, Carter MJ. Publicly reported wound healing rates: the fantasy and the reality. Adv Wound Care (New Rochelle). 2018; 7(3):77–94. doi:10.1089/wound.2017.0767.
17. Nussbaum SR, Carter MJ, Fife CE, DaVanzo J, Haught R, Nusgart M, Cartwright D. An economic evaluation of the impact, cost, and Medicare policy implications of chronic nonhealing wounds. Value Health. 2018;21(1):27–32. doi:10.1016/j.jval.2017.07.007.
18. Weiskopf NG, Weng C. Methods and dimensions of electronic health record data quality assessment: enabling reuse for clinical research. J Am Med Inform Assoc. 2013;20(1):144–151. doi:10.1136/amiajnl-2011-000681.
19. Concato J, Corrigan-Curay J. Real-world evidence — where are we now? N Engl J Med. 2022;386 (18):1680–1682. doi:10.1056/NEJMp2200089.
20. FDA. Summary of Safety and Effectiveness Data (SSED): RECELL® Autologous Cell Harvesting Device (P170031/S016). U.S. Food and Drug Administration. Approved June 6, 2023. Available at: December 22, 2023 Summary of the Safety and Effectiveness Data - RECELL Autologous Cell Harvesting Device
21. Franklin JM, Schneeweiss S. When and how can real-world data analyses substitute for randomized controlled trials? Clin Pharmacol Ther. 2017;102(6):924–933. doi:10.1002/cpt.857.
22. Perl JR, Sheth KR, Shea KG, Wall J. Hospital value committees: the role of the surgeon in new technology adoption. Surg Innov. 2021;28(4):401–402. doi:10.1177/15533506211031094.
23. Radomski TR, Good CB, Thorpe CT, Zhao X, Marcum ZA, Glassman PA, Lowe J, Mor MK, Fine MJ, Gellad WF. Variation in formulary management practices within the Department of Veterans Affairs health care system. J Manag Care Spec Pharm. 201 6;22(2):114–120. doi:10.18553/jmcp.2016.14251.
24. U.S. Food and Drug Administration (FDA). Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices: Guidance for Industry and Food and Drug Administration Staff. Silver Spring, MD: FDA; August 2017. Available at: https://www.fda.gov/media/99447/download. U.S. Food and Drug Administration (FDA). Framework for FDA’s Real-World Evidence Program. Silver Spring, MD: FDA; December 2018. Available at: https://www.fda.gov/media/120060/download. U.S. Food and Drug Administration (FDA). Real-World Data: Assessing Electronic Health Records and Medical Claims Data To Support Regulatory Decision-Making for Drug and Biological Products. Guidance for Industry. Silver Spring, MD: FDA; September 2021. Available at: https://www.fda.gov/media/152503/download.
25. Centers for Medicare & Medicaid Services (CMS). Guidance for the Public, Industry, and CMS Staff: Coverage with Evidence Development (CED). Baltimore, MD: CMS; November 2014. Available at: https://www.cms.gov/medicare-coverage-database/view/medicare-coverage-document.aspx?MCDId=27. Accessed August 2025.
26. Centers for Medicare & Medicaid Services (CMS). Medicare Evidence Development & Coverage Advisory Committee (MEDCAC) Meeting: Consideration of Real-World Evidence (RWE). Baltimore, MD: CMS; December 7, 2016. Available at: https://www.cms.gov/medicare-coverage-database/view/medcac-meeting.aspx?medcacId=72. Accessed August 2025.
27. U.S. Food and Drug Administration. Considerations for the Use of Real-World Data and Real-World Evidence to Support Regulatory Decision-Making for Drug and Biological Products. Guidance for Industry. Silver Spring, MD: FDA; August 2023. Available at: https://www.fda.gov/media/171667/download. Accessed September 2025.
28. U.S. Food and Drug Administration, Center for Devices and Radiological Health (CDRH). Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices: Guidance for Industry and Food and Drug Administration Staff. Silver Spring, MD: FDA; August 2017. Available at: https://www.fda.gov/media/99447/download. Accessed September 2025.
29. Reprise data on file.
30. Chaffin AE, et al. Cellular, acellular and matrix-like products (CAMPs) for soft-tissue reconstruction. J Wound Care. 2025;34(Suppl B):S2-S20.
31. Abdo RJ, Couch AL. Use of three-dimensional acellular collagen matrix in deep or tunneling diabetic foot ulcers: a retrospective case series. J Wound Care (North Am Suppl). 2024;33(9):1-6.
32. Snyder RJ, Cardinal M, Dauphinee D, Stavosky J. A post-hoc analysis of reduction in diabetic foot ulcer size at 4 weeks as a predictor of healing by 12 weeks. Wound Manag Prev. 2010;56(3):44-48.
33. Warriner RA, Snyder RJ, Cardinal MH. Differentiating diabetic foot ulcers that are unlikely to heal by 12 weeks following achieving 50% percent area reduction at 4 weeks. Int Wound J. 2011;8:632-637.
34. Sheehan P, Jones P, Caselli A, Giurini JM, Veves A. Percent change in wound area of diabetic foot ulcers over a 4-week period is a robust predictor of complete healing in a 12-week prospective trial. Diabetes Care. 2003;26(6):1879-1882.
35. Margolis DJ, Berlin JA, Strom BL. Which randomized controlled trials in wound care are applicable to your patient? Estimating the applicability of wound care randomized controlled trials to general wound-care populations. Wound Repair Regen. 2003;11(6):387-392.