Technology Assessment Program Skin Substitutes for Treating Chronic Wounds Technical Brief Project ID: WNDT0818 February 2, 2020 Technology Assessment Program - Technical Brief Project ID: WNDT0818 Skin Substitutes for Treating Chronic Wounds Prepared for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 5600 Fishers Lane Rockville, MD 20857 www.ahrq.gov Contract No. HHSA 290-2015-00005-I Prepared by: ECRI Institute - Penn Medicine Evidence-Based Practice Center Plymouth Meeting / Philadelphia, PA Investigators: D. Snyder, Ph.D. N. Sullivan, B.A. D. Margolis, M.D., Ph.D. K. Schoelles, M.D., S.M. ii Key Messages Purpose of Review To describe skin substitute products commercially available in the United States used to treat chronic wounds, examine systems used to classify skin substitutes, identify and assess randomized controlled trials (RCTs), and suggest best practices for future studies. Key Messages • We identified 76 commercially available skin substitutes to treat chronic wounds. The majority of these do not contain cells and are derived from human placental membrane (the placenta’s inner layer), animal tissue, or donated human dermis. • Included studies (22 RCTs and 3 systematic reviews) and ongoing clinical trials found during our search examine approximately 25 (33%) of these skin substitutes. • Available published studies rarely reported whether wounds recurred after initial healing. Studies rarely reported outcomes important to patients, such as return of function and pain relief. • Future studies may be improved by using a 4-week run-in period before study enrollment and at least a 12-week study period. They should also report whether wounds recur during 6-month followup. Disclaimer A skin substitute’s commercial availability is not a reflection of its legal status. Manufacturers self- determine whether their human cells, tissues, or cellular or tissue-based product (HCT/P) can be marketed without FDA preapproval and often misunderstand or mischaracterize the criteria they must meet for the product to be regulated solely for communicable disease risk. See 21 CFR 1271.10(a). For more information, see “FDA Announces Comprehensive Regenerative Medicine Policy Framework.” We note that FDA does not refer to any product or class of products as “skin substitutes,” and we are not proposing an official definition or classification system. The report includes many products cleared by the FDA as wound dressings via the 510(k) pathway which are not intended to treat wounds but only to cover wounds so that the natural healing process can take place. iii This report is based on research conducted by the ECRI Institute-Penn Medicine Evidence-Based Practice Center (ECRI-Penn EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. HHSA 290-2015-00005-I). The findings and conclusions in this document are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ. No statement in this article should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services. None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report. The information in this report is intended to help health care decisionmakers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information (i.e., in the context of available resources and circumstances presented by individual patients.) This report is made available to the public under the terms of a licensing agreement between the author and the Agency for Healthcare Research and Quality. This report may be used and reprinted without permission except those copyrighted materials that are clearly noted in the report. Further reproduction of those copyrighted materials is prohibited without the express permission of copyright holders. AHRQ or U.S. Department of Health and Human Services endorsement of any derivative products that may be developed from this report, such as clinical practice guidelines, other quality enhancement tools, or reimbursement or coverage policies, may not be stated or implied. Individuals using assistive technology may not be able to fully access information in this report. For assistance, contact [email protected]. Suggested citation: Snyder DL, Sullivan N, Margolis DJ, Schoelles K. Skin substitutes for treating chronic wounds. Technology Assessment Program Project ID No. WNDT0818. (Prepared by the ECRI Institute-Penn Medicine Evidence-based Practice Center under Contract No. HHSA 290-2015-00005-I) Rockville, MD: Agency for Healthcare Research and Quality. February 2020. Available at: http://www.ahrq.gov/research/findings/ta/index.html. iv Preface The Agency for Healthcare Research and Quality (AHRQ), through its Evidence-based Practice Centers (EPCs), sponsors the development of systematic reviews to assist public- and private-sector organizations in their efforts to improve the quality of health care in the United States. The Centers for Medicare and Medicaid Services (CMS) requested this report from the Evidence-based Practice Center (EPC) Program at the Agency for Healthcare Research and Quality (AHRQ). AHRQ assigned this report to the following EPC: ECRI Institute- Penn Medicine Evidence-based Practice Center (Contract Number: HHSA290201500005I). The reports and assessments provide organizations with comprehensive, evidence-based information on common medical conditions and new health care technologies and strategies. They also identify research gaps in the selected scientific area, identify methodological and scientific weaknesses, suggest research needs, and move the field forward through an unbiased, evidence-based assessment of the available literature. The EPCs systematically review the relevant scientific literature on topics assigned to them by AHRQ and conduct additional analyses when appropriate prior to developing their reports and assessments. To bring the broadest range of experts into the development of evidence reports and health technology assessments, AHRQ encourages the EPCs to form partnerships and enter into collaborations with other medical and research organizations. The EPCs work with these partner organizations to ensure that the evidence reports and technology assessments they produce will become building blocks for health care quality improvement projects throughout the Nation. The reports undergo peer review and public comment prior to their release as a final report. AHRQ expects that the EPC evidence reports and technology assessments, when appropriate, will inform individual health plans, providers, and purchasers as well as the health care system as a whole by providing important information to help improve health care quality. If you have comments on this evidence report, they may be sent by mail to the Task Order Officer named below at: Agency for Healthcare Research and Quality, 5600 Fishers Lane, Rockville, MD 20857, or by email to [email protected] Gopal Khanna, M.B.A. Arlene Bierman, M.D., M.S. Director Director Agency for Healthcare Research and Quality Center for Evidence and Practice Improvement Agency for Healthcare Research and Quality Stephanie Chang, M.D., M.P.H. Director David Niebuhr, M.D. Evidence-based Practice Center Program Task Order Officer Center for Evidence and Practice Improvement Center for Evidence and Practice Improvement Agency for Healthcare Research and Quality Agency for Healthcare Research and Quality Elise Berliner, Ph.D. Director, Technology Assessment Program Center for Evidence and Practice Improvement Agency for Healthcare Research and Quality v Acknowledgments The authors gratefully acknowledge the following individuals at ECRI Institute for their contributions to this project: Katherine Donahue, Helen Dunn, Eileen Erinoff, Gina Giradi, Kariann Hudson, Janice Kaczmarek, Laura Koepfler, Jennifer Maslin, and Michael Phillips. Key Informants In designing the study questions, the EPC consulted a panel of Key Informants who represent subject experts and end-users of research. Key Informant input can inform key issues related to the topic of the technical brief. Key Informants are not involved in the analysis of the evidence or the writing of the report. Therefore, in the end, study questions, design, methodologic approaches, and/or conclusions do not necessarily represent the views of individual Key Informants. Key Informants must disclose any financial conflicts of interest greater than $5,000 and any other relevant business or professional conflicts of interest. Because of their role as end-users, individuals with potential conflicts may be retained. The TOO and the EPC work to balance, manage, or mitigate any conflicts of interest. The list of Key Informants who provided input to this report follows: Sue Bale, OBE, FRCN, Ph.D., BA, RGN, NDN, RHV, PG Dip, Dip Nursing Director of Research and Development Aneurin Bevan University Health Board President and Journal Editor European Wound Management Association Wales, UK Barbara Bates-Jensen, Ph.D., RN, WOCN, FAAN* Professor