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: