The Health Economic Impact of Living Cell Tissue Products in the Treatment of Chronic Wounds: A Retrospective Analysis of Medicare Claims Data.

OBJECTIVE: To investigate differences in wound-related costs; product waste; lower-extremity amputations; and number of applications, hospitalizations, and emergency room visits among patients treated with three cellular and/or tissue-based products. METHODS: This retrospective intent-to-treat matched-cohort study analyzed the full Medicare claims dataset from 2011 to 2014. Patients who received either a bilayer cellular construct (BLCC), dermal skin substitute (DSS), or cryopreserved human skin allograft (CHSA) were concurrently matched for Charlson Comorbidity Index, age, sex, and region, resulting in 14,546 study patients. Key variables were reported at 60, 90, and 180 days after the first product application. RESULTS: There were no statistically significant differences in the distribution of Charlson Comorbidity Index, age, sex, and region among cohorts. Wound-related costs and product wastage were lower for CHSA patients relative to both BLCC and DSS patients at all time intervals (P < .05). Patients treated with CHSA received fewer product applications than DSS at 90 and 180 days (P < .05). Amputations were significantly higher among patients treated with DSS than either CHSA or BLCC (P < .0001). CONCLUSIONS: The data demonstrate that wound-related costs, product waste, amputations, and frequency of applications are lower for CHSA than DSS. Wound-related costs and product waste are lower for CHSA compared with BLCC. Further claims analysis and prospective clinical trials could help develop appropriate quality measures and reimbursement models to ensure smarter spending for the growing population of patients with chronic wounds.

Spray on skin for diabetic foot ulcers: an open label randomised controlled trial.

BACKGROUND: One Australian loses a limb every 3 h as a result of infected diabetic foot ulcers (DFU). This common condition accounts for substantial morbidity and mortality for affected individuals and heavy economic costs for the health sector and the community. There is an urgent need to test interventions that improve wound healing time, prevent amputations and recurrent ulceration in patients presenting with DFU whilst improving quality of life and reducing health care costs. METHODS: One hundred and fifty eligible participants will be randomised to receive an autologous skin cell suspension, also termed 'spray-on' skin (ReCell®) or standard care interventions for their DFU. The primary outcome is complete wound healing at 6 months, but participants will be followed up for a total of 12 months to enable secondary outcomes including total overall costs, ulcer free days at 12 months and quality of life to be assessed. DISCUSSION: Outpatient costs for dressings, home nursing visits and outpatient appointments are key cost drivers for DFU. If spray-on skin is effective, large cost savings to WA Health will be realised immediately through a shortened time to healing, and through a higher proportion of patients achieving complete healing. Shortened healing times may enable participants to return to work earlier. Any economic benefits are likely to be amplified across Australia and other similar demographic settings where aging populations with increased diabetes rates are considered major future challenges. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12618000511235. Registered on 9 April 2018.

Health economics for treatment of diabetic foot ulcers: a cost-effectiveness analysis of eight skin substitutes.

AIM: Skin substitutes are frequently used to treat chronic diabetic foot ulcers (DFU), and many different options are available. While the clinical efficacy of many products has been evaluated, a comprehensive cost-effectiveness analysis comparing the most popular skin substitutes and using the most recent cost data has been lacking. METHODS: This study compared eight skin substitutes using published efficacy rates combined with the Centers for Medicare and Medicaid Services (CMS) 2018 cost data. The study criteria resulted in the inclusion of seven studies that described efficacy rates for treatment of DFUs using the skin substitutes. RESULTS: The results revealed wide discrepancies between these skin substitutes for the costs of treatments and healing rates in hospital outpatient departments and physician office settings. Healing rates for 12 and 16 weeks ranged from 28% to 68%, while the average cost for treating one DFU varied from $2001 to $14,507 and $1207 to $8791 in the hospital outpatient department and physician's office setting, respectively. The estimated patient share of costs for treating a single DFU ranged from $400 to $2901 and $241 to $1758 in the hospital outpatient department and physician's office setting, respectively. Most importantly, the estimated number of wounds healed out of 100 DFUs per $1000 expenditure with each patient ranged from 3.9-26.5 DFUs in the hospital outpatient department, and 4.3-36.4 DFUs in the physicians' office setting. CONCLUSIONS: This study revealed that the costs of a skin substitute itself did not necessarily correlate with its healing efficacy. These results provide a comprehensive cost-effectiveness analysis to enable integrated health-care systems, health professionals and reimbursement payers to make informed value decisions when treating DFUs.

A prospective, randomised, controlled, multicentre clinical trial examining healing rates, safety and cost to closure of an acellular reticular allogenic human dermis versus standard of care in the treatment of chronic diabetic foot ulcers.

Acellular dermal matrices can successfully heal wounds. This study's goal was to compare clinical outcomes of a novel, open-structure human reticular acellular dermis matrix (HR-ADM) to facilitate wound closure in non-healing diabetic foot ulcers (DFUs) versus DFUs treated with standard of care (SOC). Following a 2-week screening period in which DFUs were treated with offloading and moist wound care, patients were randomised to either SOC alone or HR-ADM plus SOC applied weekly for up to 12 weeks. At 6 weeks, the primary outcome time, 65% of the HR-ADM-treated DFUs healed (13/20) compared with 5% (1/20) of DFUs that received SOC alone. At 12 weeks, the proportions of DFUs healed were 80% and 20%, respectively. Mean time to heal within 12 weeks was 40 days for the HR-ADM group compared with 77 days for the SOC group. There was no incidence of increased adverse or serious adverse events between groups or any adverse events related to the graft. Mean and median graft costs to closure per healed wound in the HR-ADM group were $1475 and $963, respectively. Weekly application of HR-ADM is an effective intervention for promoting closure of non-healing DFUs.

A comparative analysis of skin substitutes used in the management of diabetic foot ulcers.

OBJECTIVE: To compare the relative product cost and clinical outcomes of four skin substitutes used as adjunctive treatments for diabetic foot ulcers (DFUs). METHOD: Medicare claims data from 2011 to 2014 were used to identify beneficiaries with diabetes and foot ulcers. Patients treated with one of four types of skin substitute (Apligraf, Dermagraft, OASIS, and MatriStem) were identified. The skin substitutes were compared on episode length; amputation rate; skin substitute utilisation; and skin substitute costs. RESULTS: There were 13,193 skin substitute treatment episodes: Apligraf (HML) was used in 4926 (37.3%), Dermagraft (HSL) in 5530 (41.9%), OASIS (SIS) in 2458 (18.6%) and MatriStem (UBM) in 279 (2.1%). The percentage of DFUs that healed at 90 days were: UBM 62%; SIS 63%; HML 58%; and HSL 58%. Over the entire time, UBM was non-inferior to SIS (p<0.001), and either was significantly better than HML or HSL (p<0.005 in all four tests). HML was marginally superior to HSL (p=0.025 unadjusted for multiple testing). Medicare reimbursements for skin substitutes per DFU episode for UBM ($1435 in skin substitutes per episode) and SIS ($1901) appeared to be equivalent to each other, although non-inferiority tests were not significant. Both were less than HML ($5364) or HSL ($14,424) (p<0.0005 in all four tests). HML was less costly than HSL (p<0.0005). CONCLUSION: Various types of skin substitutes appear to be able to confer important benefits to both patients with DFUs and payers. Analysis of the four skin-substitute types resulted in a demonstration that UBM and SIS were associated with both shorter DFU episode lengths and lower payer reimbursements than HML and HSL, while HML was less costly than HSL but equivalent in healing. DECLARATION OF INTEREST: MM and NM are health economic consultants who completed and authored this analysis. They have no financial interest in ACell, Inc. Their fees were not contingent on the outcome of this analysis.

Methodologies in creating skin substitutes.

The creation of skin substitutes has significantly decreased morbidity and mortality of skin wounds. Although there are still a number of disadvantages of currently available skin substitutes, there has been a significant decline in research advances over the past several years in improving these skin substitutes. Clinically most skin substitutes used are acellular and do not use growth factors to assist wound healing, key areas of potential in this field of research. This article discusses the five necessary attributes of an ideal skin substitute. It comprehensively discusses the three major basic components of currently available skin substitutes: scaffold materials, growth factors, and cells, comparing and contrasting what has been used so far. It then examines a variety of techniques in how to incorporate these basic components together to act as a guide for further research in the field to create cellular skin substitutes with better clinical results.

Economic outcomes among Medicare patients receiving bioengineered cellular technologies for treatment of diabetic foot ulcers.

OBJECTIVE: To assess the real-world medical services utilization and associated costs of Medicare patients with diabetic foot ulcers (DFUs) treated with Apligraf (bioengineered living cellular construct (BLCC)) or Dermagraft (human fibroblast-derived dermal substitute (HFDS)) compared with those receiving conventional care (CC). METHODS: DFU patients were selected from Medicare de-identified administrative claims using ICD-9-CM codes. The analysis followed an 'intent-to-treat' design, with cohorts assigned based on use of (1) BLCC, (2) HFDS, or (3) CC (i.e., ≥1 claim for a DFU-related treatment procedure or podiatrist visit and no evidence of skin substitute use) for treatment of DFU in 2006-2012. Propensity score models were used to separately match BLCC and HFDS patients to CC patients with similar baseline demographics, wound severity, and physician experience measures. Medical resource use, lower-limb amputation rates, and total healthcare costs (2012 USD; from payer perspective) during the 18 months following treatment initiation were compared among the resulting matched samples. RESULTS: Data for 502 matched BLCC-CC patient pairs and 222 matched HFDS-CC patient pairs were analyzed. Increased costs associated with outpatient service utilization relative to matched CC patients were offset by lower amputation rates (-27.6% BLCC, -22.2% HFDS), fewer days hospitalized (-33.3% BLCC, -42.4% HFDS), and fewer emergency department visits (-32.3% BLCC, -25.7% HFDS) among BLCC/HFDS patients. Consequently, BLCC and HFDS patients had per-patient average healthcare costs during the 18-month follow-up period that were lower than their respective matched CC counterparts (-$5253 BLCC, -$6991 HFDS). LIMITATIONS: Findings relied on accuracy of diagnosis and procedure codes contained in the claims data, and did not account for outcomes and costs beyond 18 months after treatment initiation. CONCLUSION: These findings suggest that use of BLCC and HFDS for treatment of DFU may lower overall medical costs through reduced utilization of costly healthcare services.

Wound closure in patients with DFU: a cost-effectiveness analysis of two cellular/tissue-derived products.

OBJECTIVE: Determine the cost-effectiveness of extracellular matrix (ECM) relative to human fibroblast-derived dermal substitute (HFDS) on diabetic foot ulcer (DFU) wound closure. METHOD: Outcomes data were obtained from a 12-week, randomised, clinical trial of adults aged 18 years or older diagnosed with type 1 or type 2 diabetes with a DFU. Patients were treated with either ECM or HFDS treatment. A two-state Markov model (healed and unhealed) with a 1-week cycle length was developed using wound-closure rates from the trial to estimate the number of closed-wound weeks and the expected DFU cost per patient. Results were recorded over 12 weeks to estimate the number of closed-wound weeks per treatment and the average cost to achieve epithelialisation (primary outcome). The perspective of the analysis was that of the payer, specifically the Centers for Medicare and Medicaid Services. No cost discounting was performed because of the short duration of the study. RESULTS: The study consisted of 26 patients, with 13 in each group. In the ECM group, 10 wounds closed (77%), with an average closure time of 36 days; 11 wounds closed in the HFDS group (85%), with an average closure time of 41 days. There was no significant difference between these results (p=0.73). Over 12 weeks, the expected cost per DFU was $2522 (£1634) for ECM and $3889 (£2524) for HFDS. Patients treated with HFDS incurred total treatment costs that were approximately 54% higher than those treated with ECM. Sensitivity analyses revealed that the total cost of care for two applications of HFDS was more costly than eight applications of ECM by approximately $500 (£325). CONCLUSION: In patients with DFU, ECM yielded similar clinical outcomes to HFDS but at a lower cost. Health-care providers should consider ECM as a cost-saving alternative to HFDS. DECLARATION OF INTEREST: A.M. Gilligan, and C.R. Waycaster, are employees of Smith & Nephew Inc.. This study was funded by Smith & Nephew Inc.. A.L. Landsman, reports no conflicts of interest.

Cost-effectiveness of three adjunct cellular/tissue-derived products used in the management of chronic venous leg ulcers.

OBJECTIVES: Determine the cost-effectiveness of three topically applied cellular/tissue-derived products (CTPs) used as adjunct therapies to standard care in the management of venous leg ulcers (VLUs). METHODS: A three-state Markov model derived from the medical literature was developed to estimate the comparative cost-effectiveness of three CTPs in relation to VLU standard care. CTPs evaluated in the study included extracellular matrix (ECM), human skin equivalent (HSE), and living skin equivalent (LSE). The three Markov states included unhealed, healed, and death. A 1-year time horizon was used to determine the number of ulcer-free weeks and the expected costs of therapies. The payer perspective was taken in the analysis and only the direct costs of care were considered. Sensitivity analyses were performed to gauge model parameter uncertainty. RESULTS: The expected costs for standard care, ECM, HSE, and LSE VLU therapy were $6,132, $6,732, $10,638, and $11,237, while the expected outcomes were 24, 31, 29, and 27 ulcer-free weeks, respectively. ECM was economically dominant among the three CTPs. In the base case of ECM versus standard care, the incremental cost-effectiveness ratio for ECM therapy was $86 per ulcer-free week. Sensitivity analysis did not alter ECM dominance. Clinic visits and home health utilization exhibited the greatest influence on cost. CONCLUSIONS: ECM is the most cost-effective CTP when used in the management of VLUs as an adjunct to standard care. These findings suggest that VLU standard care therapy with ECM can yield potential cost savings and produce better outcomes than do other CTPs.

State-of-the-art wound healing: skin substitutes for chronic wounds.

The care of chronic wounds represents an important and evolving area of dermatology. With a rising prevalence of chronic wounds bearing notable effects on patient morbidity including amputations, appropriate and effective intervention to treat these debilitating wounds can make a significant clinical impact. In recent years, several advanced bioactive wound dressings have been developed to specifically treat chronic nonhealing wounds. These wound dressings encompass a wide range of products containing synthetic matrix scaffolds, animal-derived matrices, and human tissue. With several of these wound dressings, randomized controlled trials (RCTs) have demonstrated improvement in wound healing; furthermore, cost-effectiveness studies have suggested that these products may reduce the overall cost of treating a chronic wound. Familiarity with these products and their appropriate use may be helpful to dermatologists treating chronic wounds.

Cost study of dermal substitutes and topical negative pressure in the surgical treatment of burns.

BACKGROUND: A recently performed randomised controlled trial investigated the clinical effectiveness of dermal substitutes (DS) and split skin grafts (SSG) in combination with topical negative pressure (TNP) in the surgical treatment of burn wounds. In the current study, medical and non-medical costs were investigated, to comprehensively assess the benefits of this new treatment. METHODS: The primary outcome was mean total costs of the four treatment strategies: SSG with or without DS, and with or without TNP. Costs were studied from a societal perspective. Findings were evaluated in light of the clinical effects on scar elasticity. RESULTS: Eighty-six patients were included. Twelve months post-operatively, highest elasticity was measured in scars treated with DS and TNP (p=0.027). The initial cost price of treatment with DS and TNP was €2912 compared to treatment with SSG alone €1703 (p<0.001). However, mean total costs per patient did not differ significantly between groups (range €29097-€43774). DISCUSSION: Costs of the interventional treatment contributed maximal 7% to the total costs and total costs varied widely within and between groups, but were not significantly different. Therefore, in the selection of the most optimal type of surgical intervention, cost considerations should not play an important role.

Keratinocytes in the treatment of severe burn injury: an update.

Burns are among the most life-threatening physical injuries, in which fast wound closure is crucial. The surgical burn care has evolved considerably throughout the past decennia resulting in a shift of therapeutic goals. Therapies aiming to provide coverage of the burn have been replaced by treatments that have both functional as aesthetic outcomes. The standard in treating severe burns is still early excision followed by skin grafting. The use of cultured keratinocytes to cover extensive burn wounds appeared very promising at first, but the technique still has several limitations of which the long time to culture, the major costs, the risk of infection and the need for an adequate dermal layer limit clinical application. The introduction of dermal substitutes, composite grafts, tissue engineering based on stem cell application have been advocated. The aim of this review is to assess the use of cultured keratinocytes in terms of technical aspects, clinical application, limitations and future perspectives. Cultured keratinocytes are expected to keep playing a role in wound healing, especially in the field of chronic wounds. In severe burns, despite its limitations, keratinocytes can be beneficial if implemented as one of the elements in a broader wound management.