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 randomized, open-label, multicenter study of the efficacy and safety of intravesical hyaluronic acid and chondroitin sulfate versus dimethyl sulfoxide in women with bladder pain syndrome/interstitial cystitis.

AIMS: Intravesical instillation of hyaluronic acid (HA) plus chondroitin sulfate (CS) in women with bladder pain syndrome/interstitial cystitis (BPS/IC) has shown promising results. This study compared the efficacy, safety, and costs of intravesical HA/CS (Ialuril® , IBSA) to dimethyl sulfoxide (DMSO). METHODS: Randomized, open-label, multicenter study involving 110 women with BPS/IC. The allocation ratio (HA/CS:DMSO) was 2:1. Thirteen weekly instillations of HA (1.6%)/CS (2.0%) or 50% DMSO were given. Patients were evaluated at 3 (end-of-treatment) and 6 months. Primary endpoint was reduction in pain intensity at 6 months by visual analogue scale (VAS) versus baseline. Secondary efficacy measurements were quality of life and economic analyses. RESULTS: A significant reduction in pain intensity was observed at 6 months in both treatment groups versus baseline (P < 0.0001) in the intention-to-treat population. Treatment with HA/CS resulted in a greater reduction in pain intensity at 6 months compared with DMSO for the per-protocol population (mean VAS reduction 44.77 ± 25.07 vs. 28.89 ± 31.14, respectively; P = 0.0186). There were no significant differences between treatment groups in secondary outcomes. At least one adverse event was reported in 14.86% and 30.56% of patients in the HA/CS and DMSO groups, respectively. There were significantly fewer treatment-related adverse events for HA/CS versus DMSO (1.35% vs. 22.22%; P = 0.001). Considering direct healthcare costs, the incremental cost-effectiveness ratio of HA/CS versus DMSO fell between 3735€/quality-adjusted life years (QALY) and 8003€/QALY. CONCLUSIONS: Treatment with HA/CS appears to be as effective as DMSO with a potentially more favorable safety profile. Both treatments increased health-related quality of life, while HA/CS showed a more acceptable cost-effectiveness profile.

The Use of Integra Dermal Regeneration Template Versus Flaps for Reconstruction of Full-Thickness Scalp Defects Involving the Calvaria: A Cost-Benefit Analysis.

BACKGROUND: INTEGRA® Dermal Regeneration Template is a well-known and widely used acellular dermal matrix. Although it helps to solve many challenging problems in reconstructive surgery, the product cost may make it an expensive alternative compared to other reconstruction procedures. This retrospective study aims at comparing INTEGRA-based treatment to flap surgery in terms of cost and benefit. PATIENTS AND METHODS: We considered only patients treated for scalp defects with bone exposure in order to obtain two groups as homogeneous as possible. We identified two groups of patients: 17 patients treated with INTEGRA and 18 patients treated with flaps. All patients were admitted in our institution between 2004 and 2010, and presented a defect of the scalp following trauma or surgery for cancer, causing a loss of the soft tissues of the scalp with bone exposure without pericranium. To calculate the cost in constant euros of each treatment, three parameters were evaluated for each patient: cost of the surgical procedure (number of doctors and nurses involved, surgery duration, anesthesia, material used for surgery), hospitalization cost (hospitalization duration, dressings, drugs, topical agents), and outpatient cost (number of dressing changes, personnel cost, dressings type, anti-infective agents). The statistical test used in this study was the Wilcoxon Mann-Whitney (α = 0.05). RESULTS: No significant difference was characterized between the two groups for gender, age, presence of diabetes, mean defect size, and number of surgical procedures. All patients healed with good quality and durable closure. The median total cost per patient was €11,121 (interquartile range (IQR) 8327-15,571) for the INTEGRA group and €7259 (IQR 1852-24,443) for the flap group (p = 0.34). A subgroup of patients (six patients in the INTEGRA group and five patients in the flap group) showing defects larger than 100 cm2 were considered in a second analysis. Median total cost was €11,825 (IQR 10,695-15,751) for the INTEGRA group and €23,244 (IQR 17,348-26,942) for the flap group. CONCLUSION: Both treatments led to a good healing of the lesions with formation of soft and resistant tissue. No significant difference was characterized between the two groups for days of hospitalization and costs. In cases of patients with defects larger than 100 cm2 for whom major surgery is needed, the treatment with INTEGRA seemed to be less expensive than the treatment with free flaps or pedicle flaps. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the A5 online Instructions to Authors. www.springer.com/00266 .

Efficacy and safety of glucosamine sulfate in the management of osteoarthritis: Evidence from real-life setting trials and surveys.

The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) treatment algorithm recommends chronic symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) including glucosamine sulfate (GS) and chondroitin sulfate (CS) as first-line therapy for knee osteoarthritis (OA). Numerous studies are published on the use of SYSADOAs in OA; however, the efficacy of this class is still called into question largely due to the regulatory status, labeling and availability of these medications which differ substantially across the world. Examination of the evidence for the prescription patented crystalline GS (pCGS) formulation at a dose of 1500mg once-daily demonstrates superiority over other GS and glucosamine hydrochloride (GH) formulations and dosage regimens. Thus, the ESCEO task force advocates differentiation of prescription pCGS over other glucosamine preparations. Long-term clinical trials and real-life studies show that pCGS may delay joint structural changes, suggesting potential benefit beyond symptom control when used early in the management of knee OA. Real-life pharmacoeconomic studies demonstrate a long-term reduction in the need for additional pain analgesia and non-steroidal anti-inflammatory drugs (NSAIDs) with pCGS, with a significant reduction of over 50% in costs associated with medications, healthcare consultations and examinations over 12 months. Furthermore, treatment with pCGS for at least 12 months leads to a reduction in the need for total joint replacement for at least 5 years following treatment cessation. Thus, pCGS (1500mg od) is a logical choice to maximize clinical benefit in OA patients, with demonstrated medium-term control of pain and lasting impact on disease progression.

Evaluación económica del uso de condroitín sulfato y antiinflamatorios no esteroideos en el tratamiento de la artrosis. Datos del estudio VECTRA / An economic evaluation of chondroitin sulfate and non-steroidal anti-inflammatory drugs for the treatment of osteoarthritis. Data from the VECTRA study

Objetivo. El presente estudio a) estima el coste medio de un paciente con artrosis tratado durante 6 meses con condroitín sulfato (CS) o antiinflamatorios no esteroideos (AINE), y b) evalúa el impacto presupuestario para el Sistema Nacional de Salud que causaría la disminución del consumo de AINE con la administración en monoterapia o conjunta de CS. Material y método. Modelo de minimización de costes que comparó ambos tratamientos (asumiendo igualdad de eficacia), a las dosis y las pautas recomendadas, durante un período de seis meses. Los datos utilizados en el modelo se obtuvieron del estudio VECTRA, un estudio retrospectivo en el que se recogieron el consumo de recursos sanitarios de 530 pacientes con artrosis tratados con CS o AINE. La eficacia y la incidencia de efectos adversos se estimaron a partir del metaanálisis de ensayos clínicos aleatorizados. Se hicieron análisis de sensibilidad simples univariantes del caso básico. Resultados. El coste semestral por paciente tratado con CS fue de 141 €, y de 182 € en el caso de los AINE. Esto significa que si durante los 3 próximos años el 5, el 10 y el 15% de los pacientes con artrosis tratados actualmente con AINE fueran tratados con CS, se generarían ahorros para el Sistema Nacional de Salud de más de 38,7 millones de euros durante este período. Además, por cada 10.000 pacientes tratados con CS en lugar de AINE se evitarían 2.666 efectos adversos gastrointestinales, de los que 90 serían graves. Los análisis de sensibilidad confirmaron la estabilidad del caso básico en todos los supuestos considerados. Conclusiones. Comparado con los AINE, el CS es un tratamiento con menores costes y con mejor tolerancia gastrointestinal en el manejo de la artrosis (AU)

Objective. Our aim was to investigate: a) the average cost per patient with osteoarthritis treated with chondroitin sulfate compared with NSAIDs for 6 months and b) the possible impact that the reduction NSAID use due to monotherapy with or combined administration of chondroitin sulfate treatment may have on the budget of the Spanish National Health System. Methods. A cost-minimization model compared both treatments (efficacy equivalence assumption), used at the recommended doses and regimens during a 6-month period. Data used in the model was obtained from the VECTRA study, a retrospective study of 530 patients with osteoarthritis treated with chondroitin sulfate or NSAIDs that was conducted to determine the consumption of health care resources. The efficacy and incidence of adverse events was estimated from meta-analysis based on randomized clinical trials. Univariate sensitivity analysis was performed for the base case scenario. Results. The overall 6-month cost per patient given chondroitin sulfate was 141 € compared with 182 € when treated with NSAIDs. If during the forthcoming 3 years, 5%, 10%, and 15% of patients currently treated with NSAIDs would gradually be replaced by treatment with chondroitin sulfate, the expected savings for the Spanish National Health System during these 3 years would be over 38,700,000 €. In addition, 2,666 cases of gastrointestinal adverse events (including 90 serious adverse events) will have been avoided for every 10,000 patients treated with chondroitin sulfate instead of NSAID. Sensitivity analysis confirmed the strength of base-case in all scenarios. Conclusions. On the basis of these findings, chondroitin sulfate is a treatment for osteoarthritis with a lesser cost and better gastrointestinal tolerability compared with NSAIDs (AU)

Impact of chondroitin sulphate on health utility in patients with knee osteoarthritis: towards economic analysis.

OBJECTIVES: The first objective was to assess the effect of the chondroitin 4 and 6 sulphate (CS) on health-related quality of life using utility values in patients with knee osteoarthritis (OA) during a 24-month treatment course. The second objective was, using these data, to conduct economic analyses. METHODS: Data from the STOPP study was used. This study was a randomised, double-blind, placebo (PL) -controlled trial of 2-year duration. In the STOPP study, authors assessed quality of life using the Western Ontario and McMaster Osteoarthritis Index (WOMAC). WOMAC scores were translated into Health Utility Index (HUI) scores using a specific formula. Incremental cost effectiveness ratio (ICER) was calculated taking into account the cost of CS and its effect on HUI scores, compared to PL. RESULTS: At baseline, the mean (SD) HUI scores were 0.59 (0.17), and 0.59 (0.18) for the PL and CS groups, respectively (p=0.31 between the two groups). The mean (SD) HUI scores changes from baseline to 6 months were 0.02 (0.02), and 0.05 (0.01) for the PL and CS groups, respectively (p=0.03). After 24 months of follow-up, HUI score increases by 0.04 (0.02) in the PL group and by 0.05 (0.02) in the CS group (p=0.37). Using the price bracket of CS in Europe, ICER assessment always resulted in a cost below €30,000 per QALY gained, after 6, 12 and 24 months of treatment. CONCLUSION: CS treatment increases health utilities in patients with knee OA compared to PL over the first 6 months of treatment. Economic evaluation based on these data suggests that CS treatment could be considered as cost-effective in patients with knee OA up to a period of 24 months. A limitation in this study is the absence of direct utility assessment as well as the absence of effective treatment as comparator.

Identification of the origin of chondroitin sulfate in "health foods".

Twelve "health foods" products containing chondroitin sulfate (CS) were purchased from the Japanese market and the origin of the CS was investigated by conducting disaccharide compositional analysis after enzymatic depolymerization and by 1H-NMR spectroscopy. Nine of the 12 products had labels indicating that the origin of the CS was shark cartilage. However, two of them were found to contain mammalian CS. Next, we compared the ratio of the sulfate group to the galactosamine residue after the acid hydrolysis of CS. The results suggest that all of the CS from sharks had a ratio of more than 1.0, while the CS from mammals had a ratio of less than 1.0. Since this comparative analysis does not require expensive purified enzyme, it would be an economical way to identify the origin of CS in "health foods." Being able to determine the origin of the ingredients in natural products is very important for ensuring their quality, safety, and efficacy. Therefore, we think that regulatory requirements for accurately indicating the origin of "health foods" and effective enforcement of these requirements are needed.

Chondroitin sulfate for interstitial cystitis.

(1) Chondroitin sulfate solution 2.0% is a glycosaminoglycan (GAG) replenishment therapy instilled into the bladder of GAG-deficient patients with interstitial cystitis (IC). (2) Two non-randomized, uncontrolled pilot studies report improvements in patient-reported symptoms after the use of chondroitin sulfate for one year. Prospective, randomized, head-to-head trials are needed to assess the effectiveness of this technology compared with other IC therapies. (3) The cost and demand for this technology are low, but there could be a significant impact on clinics that administer treatment, if uptake increases.

[Pharmacoeconomic aspects of use of structum in osteoarthrosis]. / Farmakoékonomicheskie aspekty primeneniia struktuma pri osteoartroze.

AIM: To study cost-effect efficiency of structum in patients with knee and hip joint osteoarthrosis (OA) in a multicenter trial. MATERIAL AND METHODS: The trial enrolled 192 patients with OA. 110 patients had knee joint OA and 82 patients hip joint OA. The patients received structum for 6 months. Efficacy of the treatment was assessed before use of structum and after it by standard methods. Integral effect of therapy was estimated according to the special program complex. The cost of the drug therapy included the cost of structum and nonsteroid anti-inflammatory drugs (NSAID) on conversion to 1 mg of diclofenac plus the cost of treating side effects. The efficacy per unit cost was calculated by the formula: E1xC2/E2xC1, where E1--integral efficacy of therapy before using structum, E2--integral efficacy of therapy in administration of structum, C1--cost of drug therapy, C2--cost of drug therapy in using structum. RESULTS: E2 was equal to 94% for knee joints OA and 92% for hip joint OA, E1 and C1--21 and 19%, respectively. C2 was equal to 108.43$ for knee joint OA and 106.97 for hip joint OA, C1--29.3 and 27.44, respectively. The efficacy per unit cost for knee joint OA was 94 x 29.3/21 x 108.3 = 1.21, for hip joint OA 92 x 27.44/19 x 106.97 = 1.24. The figures evidence for much higher efficacy per unit cost of structum vs routine NSAID. CONCLUSION: The multicenter trial gave grounds not only for clinical efficacy of structum vs NSAID but also for cost-effect advantage of structum in therapy of OA.

Danaparoid sodium.

Danaparoid sodium (Orgaran, Organon) is a heparinoid glycosamino-glycuronan antithrombotic agent approved for the prophylaxis of post-operative deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE) in patients undergoing elective hip replacement surgery. Danaparoid is a low molecular weight heparinoid consisting of a mixture of heparan sulphate (84%), dermatan sulphate (12%) and small amounts of chondroitin sulphate (4%), whose antithrombotic activity has been well established. Its pharmacological effect is exerted primarily by inhibiting Factors Xa (FXa) and IIa (FIIa) at a ratio greater than heparin, with a minimal effect on platelet function. Danaparoid exhibits low cross-reactivity with heparin-induced antibodies when compared with heparin or low molecular weight heparins (LMWH), thereby making it an excellent choice for the management of heparin-induced thrombocytopenia (HIT). It has excellent bioavailability following s.c. injection. Danaparoid has little effect on routine coagulation tests (activated partial thromboplastin time [aPTT], prothrombin time [PT], and thrombin time [TT]). Patients with elevated serum creatinine should be monitored carefully. For its FDA approved indication (DVT prophylaxis during hip replacement surgery), its cost per day is approximately eight times more than LMWH. Even though monitoring is not routinely necessary according to the manufacturer for its approved indication, monitoring is frequently necessary when it is used in other clinical scenarios. Its higher cost than comparable therapies for DVT prophylaxis and the low availability of the FXa assay in most non-tertiary care hospitals has limited the widespread use of danaparoid. Danaparoid has been found to be effective in the treatment of HIT although this is an off label use, despite being the most frequent reason why danaparoid is used.

[Chondroitin sulfates (CS 4&6): practical applications and economic impact]. / Les chondroïtines sulfates (CS 4&6): schéma d'utilisation et impact économique.

UNLABELLED: PROVEN CLINICAL BENEFIT: It has been demonstrated that CS 4&6 administered at the dose of 1200 mg/d for several months is more effective than placebo and as effective as nonsteroidal anti-inflammatory drugs (NSAID) in providing pain relief and improving joint function without risk in subjects with osteoarthritis of the hip and the knee. The beneficial effect persists several weeks after the end of treatment. These advantages should thus have an overall cost-lowering effect. EVALUATION OF THE ECONOMIC IMPACT: A medico-economical study was conducted to reevaluate the beneficial effect of CS 4&6 on the quantity of NSAID prescriptions in France and to determine whether the drug was used correctly in accordance with indications at an adequate dose and treatment duration. DATABASES USED: Two databases, IMS a data bank on medical prescriptions in France, and THALES which gives information on prescriptions by 300 general practitioners, allowed a dynamic analysis of the medical files of 11,000 patients with osteoarthritis. ECONOMICAL BENEFIT: The cost of NSAID prescriptions by general practitioners was reduced by an estimated 67% in patients treated with CS 4&6. In terms of the quantity of NSAID used, the reduction in the CS 4&6 treated group was 63% and 85.3% respectively in patients treated by generalists and by specialists. The quantity of NSAIDs prescribed was reduced by two-thirds when CS 4&6 were represcribed. The cost related to CS 4&6 treatment was compensated for by the reduction in physiotherapy costs and by fewer co-prescriptions for gastroprotective drugs. This study confirmed the randomized clinical studies demonstrating that a regimen of CS 4&6 for several weeks at the dose of 1200 mg/d lowers prescriptions of NSAID which can be completely avoided in nearly half the cases.