Cost-Utility Analysis of Negative Pressure Wound Therapy Compared With Traditional Wound Care in the Treatment of Diabetic Foot Ulcers in Iran

According to the fourth round of the periodic National Survey of Risk Factors for Non-communicable Diseases project in 2011 (SuRFNCD-2011), 4.5 million adults in Iran had diabetes, which is expected to reach 9.2 million by 2030.¹ In 2009, total costs of type 2 diabetes in Iran were estimated at $3.78 billion, including $2 billion direct (ie, medical and non-medical) costs and $1.78 billion indirect costs. Most treatment costs for patients with diabetes are related to complications of this disease,² with lower limb ulcers, including foot ulcers, being the most common complications of diabetes.³ Diabetic foot ulcers (DFUs) are the main reason for hospitalization and amputation⁴; worldwide, approximately 15% of patients with diabetes also have DFUs.³ Managing diabetic ulcers is a complicated process, and the ulcers may take months or years to heal.⁵ Care and treatment of DFUs have significant clinical and economic challenges for both patients and health care systems.⁶ On average, ulcer treatment costs were estimated to be about $13179 per each episode. With increasing level of severity, the cost ranged between $1892 (level 1) and $27721 (levels 4 and 5). Inpatient hospital expenditures are the most expensive treatments for DFU.⁷ Clinical factors such as ulcer depth and surface, the healing rate, severity of infection, and ischemia can affect the cost of treatment as well. If the advantage of healing is negligible in comparison to treatment damage, the last treatment option is amputation. In cases of re-infection, re-amputation will occur, which would increase the cost burden imposed on the community.⁸

The global DFU prevalence rate is 6.3% (95% confidence interval [CI], 5.4%–7.3%), and the DFU prevalence rate in Asia is reported as 5.5%.⁹ Prevention of this complication can relieve direct and indirect cost burdens on society. Notably, the prevalence rate of DFU was estimated to be 6.4% in Iran.¹⁰ Based on the results of a study conducted in Iran, of the total costs of diabetes complications, 10.7% were related to DFU (US $107.1 million).²

The use of treatment strategies that are both cost effective and clinically effective is one of the main goals of DFU management. Currently, a wide range of dressings are used in DFU treatment, including traditional wound dressing, wet wound dressing, foam and alginate dressing, hydrogels, and hydrocolloids.¹¹

Wound dressing is recommended as one of the best practices for wound management in patients with DFU¹²; however, some clinical evidence on the effectiveness of these dressings in DFU treatment is still unclear. In many studies, there were no significant improvements in the wound healing process using dressing treatment.¹³

Negative pressure wound therapy (NPWT; also known as vacuum-assisted wound closure) is a relatively innovative strategy in ulcer treatment. In this technique, the negative pressure imposed into the wound enhances the wound healing process and facilitates the discharge of secretions.¹⁴ The decrease in wound healing time, wound depth and surface, and number of amputations are known benefits of NPWT.¹⁵ Clinical efficacy of NPWT can lead to the reduction of resource usage and consequently to decreased treatment cost for patients and health care providers. Therefore, NPWT technology can be a cost-effective alternative for both wound care recipients and health care providers. The results of economic evaluation studies showed that, in contrast to patients undergoing advanced wound treatment, patients treated with NPWT have both more quality-adjusted life years (QALY) and better wound healing with lower costs.^5,16

Cost-utility analysis examines technical and allocative efficiencies and incorporates some changes in the quantity of life (mortality) and changes in the quality of life (morbidity) into a single unit of QALYs. This economic evaluation method compares the incremental cost of a particular treatment to the incremental health gains expressed in QALYs. In this case, the incremental cost-utility ratio (ICER) is usually expressed as the incremental cost to gain an extra QALY. Moreover, it provides a context to make judgments on the value for money in a given intervention usage. The ICER is the ratio between the differences in costs and benefits of 2 interventions.¹⁷

Numerous studies have been conducted on the cost-effectiveness of NPWT compared with conventional dressings. The results of these studies showed that NPWT has been more cost-effective than standard dressings and other comparators.^16,18,19

Negative pressure wound therapy has emerged as a promising option that may result in better health outcomes. Despite the efficacy of NPWT compared with traditional wound dressing treatment, there is little research conducted on the cost-effectiveness of this technology to date, especially in economically developing countries, and the evidence is not strong enough to support this method’s cost-effectiveness. The purpose of this study was to analyze the cost-utility of NPWT compared with traditional wound care (TWC) for the treatment of patients with DFU in Iran from the perspective of health care providers.

This economic evaluation study was conducted in 2016. In order to simulate the health status of patients with DFU (NPWT = 100; TWC = 100) under different health conditions, the Markov model approach was used in this study. The Markov model is generally suitable for examining chronic and recurring conditions (similar to the alternatives investigated in this study).^20,21 The initial structure of the Markov model in this study was based on models used in previous studies.^5,16 The initial model also was adjusted for the treatment process of Iranian patients with DFU. Moreover, information on the outcomes and transition rates of different health diagnoses were extracted from the related published sources.^5,16 The time period of this study was considered to be 1 year and based on monthly cycles (ie, 12 cycles). The Markov model structure used in this study is shown in Figure 1. The health diagnoses considered in this study included the following: uninfected, infected, infected post-amputation, healed, healed post-amputation, amputation, and death. The transition between different health conditions was determined based on the DFU development, so that a person with DFU may clinically go through different health conditions, as shown in Figure 1. Based on the natural history of DFU, there are some clinical impossibilities to the transition between some diagnoses (ie, there is no possibility for patients to be directly transferred from an infected state to a healed state or from death to another health state). The analysis of cost-effectiveness and sensitivity for uncertain parameters was performed using TreeAge Pro 2011 (TreeAge LLC). An expert panel validated the model, including clinicians specialized in diabetes, health economics, and health policy.

Transition rates
Monthly transition rates between different health states indicated the probability of moving between 2 possible health conditions during 1 month. For example, with NPWT, the probability of change of an uninfected wound of the diabetic foot into an infected wound is 3.6%, but the probability is 4.3% when using TWC. Also with NPWT, the probability that the infected wound would result in amputation is 1.1%, vs 3.8% with TWC. Correspondingly, these probabilities were derived from studies by Flack et al⁵ (1000 hypothetical patients) and Whitehead et al¹⁶ (1000 hypothetical patients) on NPWT and wound dressing strategies (Table 1).

Resource use
The resources used for each health diagnosis were estimated monthly and separately based on inpatient (ie, inpatient days, nursing visits, antibiotics, orthopedic appliances, amputation, prostheses, and materials/dressings) and outpatient care (ie, physician visits and tests). The resources used to estimate the inpatient costs were obtained from medical records of 200 patients who were admitted to university-affiliated hospitals in Tehran, Iran. The resources used based on various health diagnoses are shown in Table 2.

Costs
The present study investigated the cost-effectiveness of NPWT compared with TWC treatment strategies from the perspective of health care providers. To calculate monthly costs per each health state for NPWT and TWC strategies, unit costs of inpatient days, nursing visits, physician visits, amputation surgery, and DFU dressing were extracted from the Relative Value of Health Services,²² which were then multiplied by their relevant monthly resource usage. Costs of antibiotics, orthopedic appliances, prostheses, and tests were obtained directly from the patient’s medical records, with the exception of the cost of mortality, which was not considered in this study (Table 3).

Over 1 month, NPWT was performed in 3-day sessions 4 times. During treatment, the amount of negative pressure varied according to the progress of treatment (12 times/month). TWC was implemented every day (30 times/month). To calculate monthly dressing, wound expert, and nursing costs per patient for these 2 treatment strategies, the authors multiplied dressing change per month by cost per dressing change (Table 4).

Afterward, all costs were converted into US dollars using an average exchange rate based on the rate claimed by the Central Bank of Iran (in 2016, US $1 = 32 000 rials)

Utility weights
Utility weights needed to calculate QALYs were derived from the published literature (Coffey et al,²³ n = 2048 subjects with type 1 and type 2 diabetes; Whitehead et al,¹⁶ n = 1000 hypothetical patients). If there was a variation in utility values in the studies, the mean of utility values was considered as the utility weight. Utility weights in a plausible range in the sensitivity analysis section were considered and then analyzed. Notably, the utility value for mortality was considered zero (Table 5).

Time period
A 1-year time period was considered for calculation of costs and outcomes; therefore, the discount rate was not considered for payoffs.

Outcomes
Model effects were expressed as QALYs (utility weights of health diagnosis × length of life in that condition). Economic evaluation findings were reported in terms of ICER.

Sensitivity analysis
In order to analyze sensitivity,  uncertainty parameters (ie, costs and effects) were inserted with a sensible range in a Tornado diagram for examining the sensitivity of model results to the variables of costs and effects. Because cost variables may be significantly affected by the economic conditions of Iran and utility values may be differently reported in various studies, costs and effects have changed in the range of ± 30% and ± 20%, respectively.

Base-case analysis results
As shown in Table 6, the expected costs per patient per year using a NPWT treatment strategy ($5165 ± 3258) were $4668 lower than those of a TWC treatment strategy ($9833 ± 5861). The corresponding QALYs were 0.1052 higher for the NPWT (8.90259) compared with TWC (8.79739). Consequently, this resulted in an ICER of - $44 370 per QALY gained. With its greater QALYs and lower costs, NPWT is considered the more effective wound treatment strategy.

Sensitivity analysis
The Tornado diagram represents the impact on the ICER when varying each of the parameters (Figure 2). Due to the 1-year period of this study, the discount rate was considered neither in the initial analysis, nor in the sensitivity analysis. Based on the findings shown in Figure 2, cost variations had no effect on the prominence of NPWT; however, when the utility value of healed state decreased by 20%, the ICER result was $143874.60 per QALY, which means that NPWT was placed in the first region of the cost-effectiveness plan (ie, higher cost, greater effectiveness). In this case, choosing the most cost-effective treatment option will be dependent on the maximum willingness to pay.

The results of this study indicate that NPWT is less costly and more effective than TWC; thus, it can be considered as a preferred wound management strategy. The results also show that the ICER of NPWT therapy compared with TWC was -$44370 per QALY; NPWT is a more cost-effective alternative for the treatment of patients with DFU. Varying uncertain parameters (cost and effectiveness) did not change the dominant strategy. In general, NPWT reduces the number of patients who transfer from an infected state to an amputation state, which results in fewer amputations. In addition, the probability of achieving a healed state is higher in NPWT compared with that of TWC; this imposes less costs to both payers and patients.

Well-designed clinical trials have been conducted on the effectiveness of NPWT^24-27;however, economic evaluation studies comparing cost and clinical effectiveness of NPWT and TWC are limited. Moreover, the results of 2 important studies on economic evaluation of NPWT in comparison to the traditional (ie, saline gas) and advanced treatment options (ie, skin replacement) in patients with DFU indicated that NPWT resulted in a higher QALYs as well as a lower cost.^5,28 The results of the study by Fleck et al⁵ showed that QALYs per patient in the NPWT and traditional dressing groups was 0.53 and 0.52, respectively. Meanwhile, the average costs of NPWT and traditional treatment per patient were $57944 and $79951, respectively. Therefore, NPWT was more cost-effective, which created more QALYs compared to the traditional treatment.⁵ The results of a cohort study by Whitehead et al¹⁶ suggested that NPWT gained 3 more QALY units and €4 million ($4.68 million) fewer costs when compared with advanced wound therapy; therefore, it is considered the more effective wound treatment alternative. In addition, a clinical trial comparing NPWT with traditional treatment showed that the cost of health care providers (as a specialist in wound dressing) per day of NPWT was €81 ($91.84)—traditional treatment cost €176 ($200).²⁸ This difference was statistically significant, but this study showed that cost of consumables was higher for NPWT vs the comparator. A study conducted by Vaidhya et al²⁹ suggested that  NPWT can be economically considered as a cost-effective alternative compared to saline gas.²⁹ A systematic review on the cost-effectiveness of NPWT suggested that, despite the fact that many health care providers have the impression that NPWT is more expensive than its alternatives, this technology is actually less costly given the total cost of wound treatment. Based on these findings, the authors conclude that widespread use of this technology in wound management and treatment can reduce costs and  improve quality of life for patients.⁴ The 1-year time period of this study makes long-term effectiveness and costs untraceable in NPWT. A study over a longer time period that follows the long-term benefits of NPWT, including evaluating reduced rates of amputation and disability, may provide a more complete perspective on this therapeutic option. It is suggested that the use of NPWT in wounds other than DFU be investigated in future studies. Also, the budget impacts of NPWT technology and estimation of its financial burden on health care systems and providers require more research.

These study findings should be interpreted and generalized to settings outside of Iran with caution. The results are influenced by country-specific context such as types and characteristics of health systems reimbursement policies, relative prices, clinical practices, and local costs.³⁰ It is important to mention that this study can improve the available information on the economic aspects of the field in Iran, with the intention of supporting health professionals and policymakers. Moreover, it can provide adequate information to aid in decision-making on DFU interventions, which may result in providing more cost-effective treatments while managing scarce resources.

There are some limitations related to this study. First, the study was conducted from the provider’s perspective. The authors suggest conducting future studies from a social perspective, which is more complete and considered to be best practice in economic evaluation studies that include all the costs and outcomes associated with a technology. The second limitation is related to the lack of Iranian data on transition probabilities, quality of life, and utility weights. In the present study, the researchers used data from other countries. The lack of locally available outcome (effectiveness) data indicates the need for more study in this arena to provide more accurate local economic evaluations. A third limitation was the 1-year time horizon of the study. Due to the chronic nature of the DFU, longer-term economic modeling would result in a clearer picture when comparing the technologies and their costs. Further, to address the uncertainty related to the Markov model, comprehensive types of sensitivity analyses should be used.³¹

The study results indicate that NPWT for DFU management is less costly and more effective compared with TWC, thus it is considered as the preferred alternative. Based on these findings, the improved patient outcomes and reduced wound treatment costs compensate for the investment in this technology. In addition, the availability of insurance coverage for this technology makes it more accessible for patients with DFU.

Authors: Vahid Alipour, PhD¹; Aziz Rezapour, PhD¹; Mehdi Ebrahimi, MD²; and Jalal Arabloo, PhD¹

Affiliations: ¹Health Management and EconomicsResearch Center, Iran University of Medical Sciences, Tehran, Iran; and ²Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

Correspondence: Jalal Arabloo, PhD, Assistant Professor, Iran University of Medical Sciences, Health Management and Economics Research Center, Tehran, Tehran 1996713883 Islamic Republic of Iran; arabloo_j64@yahoo.com

Disclosure: This study was funded and supported by Iran National Institute of Health Research, Tehran University of Medical Sciences; Grant No: 93264.