Skin Substitutes for Adults With Diabetic Foot Ulcers and Venous Leg Ulcers: A Health Technology Assessment.

Background: Wounds may be caused in a variety of ways. Some wounds are difficult to heal, such as diabetic foot ulcers and venous leg ulcers. We conducted a health technology assessment of skin substitutes for adults with neuropathic diabetic foot ulcers and venous leg ulcers, which included an evaluation of effectiveness, safety, cost-effectiveness, the budget impact of publicly funding skin substitutes, and patient preferences and values.

Methods: We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using the Cochrane risk-of-bias tool for randomized studies (version 2), and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature search and conducted a cost-utility analysis with a 26-week time horizon from a public payer perspective. We also analyzed the budget impact of publicly funding skin substitutes in adults with diabetic foot ulcers and venous leg ulcers in Ontario. We explored the underlying values, needs, and priorities of those who have lived experience with diabetic leg ulcers and venous leg ulcers, as well as their preferences for and perceptions of skin substitutes.

Results: We included 40 studies in the clinical evidence review. Adults with difficult-to-heal neuropathic diabetic foot ulcers who used dermal (GRADE: High) or multi-layered (GRADE: Moderate) skin substitutes as an adjunct to standard care were more likely to experience complete wound healing than those whose who used standard care alone. Adults with difficult-to-heal venous leg ulcers who used dermal (GRADE: Moderate) or multi-layered (GRADE: High) skin substitutes as an adjunct to standard care were more likely to experience complete wound healing than those who used standard care alone. The evidence for the effectiveness of epidermal skin substitutes was inconclusive for venous leg ulcers because of the small size of the individual studies (GRADE: Very low). We found no studies on epidermal skin substitutes for diabetic foot ulcers. We could not evaluate the safety of skin substitutes versus standard care, because the number of adverse events was either very low or zero (because sample sizes were too small).In our economic analysis, the use of skin substitutes as an adjunct to standard care was more costly and more effective than standard care alone for the treatment of difficult-to-heal diabetic foot ulcers and venous leg ulcers. For diabetic foot ulcers, the incremental cost-effectiveness ratio (ICER) of skin substitutes plus standard care compared with standard care alone was $48,242 per quality-adjusted life-year (QALY), and the cost per ulcer-free week was $158. For venous leg ulcers, the ICER was $1,868,850 per QALY, and the cost per ulcer-free week was $3,235. At the commonly used willingness-to-pay of $50,000 per QALY, the cost-effectiveness of skin substitutes plus standard care versus standard care alone was uncertain (47% probability of being cost-effective) for diabetic foot ulcers and highly unlikely (0% probability of being cost-effective) for venous leg ulcers. At the commonly used willingness-to-pay of $100,000 per QALY, the cost-effectiveness of skin substitutes plus standard care versus standard care alone was moderately likely (71% probability of cost-effectiveness) for people with diabetic foot ulcers and highly unlikely (0% probability of being cost-effective) for people with venous leg ulcers. The annual budget impact of publicly funding skin substitutes in Ontario over the next 5 years would range from an additional $0.17 million in year 1 to $1.2 million in year 5 for people with diabetic foot ulcers, and from $1 million in year 1 to $7.7 million in year 5 for people with venous leg ulcers.Direct patient engagement consisted of three participants for this assessment and 51 from previous health technology assessments that addressed interventions for diabetic foot ulcers and venous leg ulcers. Participants spoke of the negative impact on their quality of life with regard to mobility, employment, social activities, and emotional and mental health. No participants had direct experience using skin substitutes, but participants were open to this treatment option. Barriers to access included the limited use of skin substitutes across Ontario, lack of knowledge of skin substitutes among people with diabetic foot ulcers and venous leg ulcers, and cost.

Conclusions: Dermal and multi-layered skin substitutes, when used as an adjunct to standard care, were more effective than standard care alone in completely healing difficult-to-heal neuropathic diabetic foot ulcers and venous leg ulcers in adults. Using skin substitutes as an adjunct to standard care was more costly and more effective than standard care alone for the treatment of difficult-to-heal neuropathic diabetic foot ulcers and venous leg ulcers. For adults with diabetic foot ulcers, the likelihood of skin substitutes being cost-effective compared with standard care depends on the willingness to pay. The likelihood of skin substitutes being cost-effective compared with standard care is uncertain at $50,000 per QALY and moderately likely at $100,000 per QALY. For adults with venous leg ulcers, skin substitutes were highly unlikely to be cost-effective compared with standard care. We estimated that publicly funding skin substitutes in Ontario would result in additional costs of $3 million and $20 million over the next 5 years for people with diabetic foot ulcers and venous leg ulcers, respectively. The people with diabetic foot ulcers and venous leg ulcers we spoke with were open to using skin substitutes as a treatment option.