A Cost-Effectiveness Analysis Comparing Single-use and Traditional Negative Pressure Wound Therapy to Treat Chronic Venous and Diabetic Foot Ulcers

Lower extremity ulcers such as venous leg ulcers (VLUs) and diabetic foot ulcers (DFUs) have a major clinical and economic impact on patients and providers. Purpose: The purpose of this economic evaluation was to determine the cost-effectiveness of single-use negative pressure wound therapy (sNPWT) compared with traditional NPWT (tNPWT) for the treatment of VLUs and DFUs in the United States. Methods: A Markov decision-analytic model was used to compare the incremental cost and ulcer weeks avoided for a time horizon of 12 and 26 weeks using lower extremity ulcer closure rates from a published randomized controlled trial (N = 161) that compared sNPWT with tNPWT. Treatment costs were extracted from a retrospective cost-minimization study of sNPWT and tNPWT from the payer perspective using US national 2016 Medicare claims data inflated to 2018 costs and multiplied by 7 to estimate the weekly costs of treatment for sNPWT and tNPWT. Two (2) arms of the model, tNPWT and sNPWT, were calculated separately for a combination of both VLU and DFU ulcer types. In this model, a hypothetical cohort of patients began in the open ulcer health state, and at the end of each weekly cycle a proportion of the cohort moved into the closed ulcer health state according to a constant transition probability. The costs over the defined timescale were summed to give a total cost of treatment for each arm of the model, and then the difference between the arms was calculated. Effectiveness was calculated by noting the incidence of healing at 12 and 26 weeks and the total number of open ulcer weeks; the incremental effectiveness was calculated as sNPWT effectiveness minus tNPWT effectiveness. Data were extracted to Excel spreadsheets and subjected to one-way sensitivity, scenario (where patients with unhealed ulcers were changed to standard care at 4 or 12 weeks), probabilistic, and threshold analyses. Results: sNPWT was found to provide an expected cost saving of $7756 per patient and an expected reduction of 1.67 open ulcer weeks per patient over 12 weeks and a cost reduction of $15 749 and 5.31 open ulcer weeks over 26 weeks. Probabilistic analysis at 26 weeks showed 99.8% of the simulations resulted in sNPWT dominating tNPWT. Scenario analyses showed that sNPWT remained dominant over tNPWT  (cost reductions over 26 weeks of $2536 and $7976 per patient, respectively). Conclusion: Using sNPWT for VLUs and DFUs is likely to be more cost-effective than tNPWT from the US payer perspective and may provide an opportunity for policymakers to reduce the economic burden of lower extremity ulcers.

Lower extremity ulcers such as venous leg ulcers (VLU) and diabetic foot ulcers (DFU) have a major impact on quality of life and impose a substantial cost burden on the United States health system.¹  To exemplify, the point prevalence of chronic wounds and wound-related infections in 2014 in the US among the Medicare population was estimated to be 14.5%,² and the annual incidence rate of VLUs in the US (2007–2011) was reported to be approximately 2.2 million annually.³ A 2017 review⁴ of global DFU prevalence in patients with diabetes mellitus (DM) found North America had the highest prevalence at 13%.  According to a 2012 international consensus,⁵ the impact of living with these chronic ulcers takes its toll on patients, resulting in reduced well-being, psychosocial impact, and potentially social exclusion. This problem is not likely to improve in the near future: increasing long-term chronic disease and an aging population infer the prevalence of chronic ulcers, including both VLUs and DFUs, is likely to increase.^1,6,7  At the same time, while need is growing, health care systems across the world are trying to control cost.
A 2018 retrospective analysis² of Medicare data concluded that spending associated with the management of wounds is substantially greater than previously thought. Total annual Medicare spending in 2014 for all wound types was estimated to be $28.1 to $96.8 billion (depending on the assumptions used). Annual expenditure on DFUs was the second highest at $6.2 to $18.7 billion. The authors² highlighted that expenditure on wound care was highest for hospital outpatients ($9.9–$35.8 billion), with an increasing proportion of costs incurred in the outpatient care setting as part of a “shift” from inpatients to outpatients. Another study³ specific to VLUs, using 2 large claims databases, estimated that the annual cost to the US payer (Medicare and private insurers) was $14.9 billion.

Retrospective cost analyses and discussion publications suggest that 1 important clinical outcome in the treatment of chronic ulcers, time to ulcer closure, is also a key cost driver, and that prolonged treatment duration is associated with higher resource utilization and the associated cost of care.^8-11 Therefore, clinical strategies that may reduce time to closure are an important consideration for decision-makers associated with the provision of wound care.⁸

Systematic reviews suggest that negative pressure wound therapy (NPWT) may be a potential strategy for the treatment of open ulcers.^12,13 A recent 1044-patient meta-analysis¹⁴ confirmed the clinical efficacy (in terms of healing time, reduction in ulcer area, and amputation risk) of traditional NPWT (tNPWT) compared to various advanced wound dressings and conventional moist gauze for the treatment of DFUs. A systematic review, a randomized controlled trial (RCT), and case series^15-18 demonstrated the benefit of tNPWT in treating VLUs compared with a range of different controls.

Traditional NPWT is delivered by means of a reusable pump connected to a disposable canister. The development of single-use NPWT (sNPWT) has provided the option of using smaller, lighter, portable canisterless devices.¹⁸ A 161-patient RCT¹⁹ comparing sNPWT (PICO Single Use Negative Pressure Wound Therapy System, Smith & Nephew) with tNPWT in VLU and DFU care showed that, after 12 weeks, wound closure occurred in 45% of participants in the sNPWT group compared with 22.2% of those in the tNPWT group (P = .002). This study¹⁹ also reported higher patient satisfaction scores with the sNPWT device compared to tNPWT and a lower frequency of discontinuation due to treatment-related wound deterioration in the sNPWT group.

Although the effectiveness of sNPWT in direct comparison with tNPWT has been demonstrated,¹⁹ its relative cost-effectiveness has not been investigated. The purpose of this economic evaluation was to use a decision-analytic model to determine the cost-effectiveness of sNPWT compared with tNPWT for the treatment of VLUs and DFUs in the US.

Decision-analytic models are widely used to determine the cost-effectiveness of 1 treatment or health care program compared with another. The authors constructed a 2-state Markov model similar to that used by Romanelli et al²⁰ in a cost-effectiveness analysis of extracellular matrix versus standard care for the treatment of VLUs. The model was implemented using Microsoft Excel (Microsoft Corporation). The Markov modelling approach is useful for estimating costs and consequences for chronic conditions that change over time; it assumes that a cohort of patients begins in a defined health state and then patients transition over time to other health states at defined intervals (cycles). The model used in the current study had time horizons of 12 weeks and 26 weeks and a cycle length of 1 week (to reflect wound assessment practice).²¹ In this model, a hypothetical cohort of patients began in the open ulcer health state, and at the end of each weekly cycle a proportion of the cohort moved into the closed ulcer health state according to a constant transition probability. Closed ulcer is an absorbing state; patients cannot return to the open ulcer health state.

This methodology assumes these transitions occur at the start of each cycle, whereas in reality the transition could occur at any time within the cycle. For this reason, a correction often is made under the assumption that the transition occurs halfway through the cycle. Because in this case the cycle length was short (ie, 1 week), this correction was not deemed necessary.

It is standard practice to define the perspective of an economic model. This is particularly important in determining what costs are included in the model as well as their values. In this case, the perspective was the US payer; this study employed treatment costs from an analysis of Medicare claims data.²² Sometimes costs and effects are discounted to take account of the time at which the costs and effects are evaluated. In this study, because the time horizon of this model was less than 1 year, neither costs nor effects were discounted.

Two (2) arms of the model, tNPWT and sNPWT, were calculated separately for a combination of both VLU and DFU ulcer types in the proportions reported by Kirsner et al¹⁹ (37.3% DFU). The model assumptions are shown in Table 1. Open ulcer to closed ulcer transition probabilities were calculated using ulcer closure rates reported from the recent 161-patient RCT.^19,23 Ulcer recurrence was not included in the model; therefore, the transition probability for closed ulcer to open ulcer was set to zero. Delhougne et al²² recently estimated the cost per day for sNPWT and tNPWT from the payer perspective using US national Medicare claims data, assuming 2016 Medicare rates. Their analysis included claims data from Medicare Parts A and B over a wide range of health care settings and services. These unit costs were inflated to 2018 costs using health care inflation indices (US Bureau of Labor Statistics²⁴) and multiplied by 7 to estimate the weekly costs of treatment for sNPWT and tNPWT (see Table 1).

The costs over the defined timescale were summed to give a total cost of treatment for each arm of the model. The difference (the incremental cost) was calculated as the total cost for sNPWT minus the total cost for tNPWT. Effectiveness was calculated 2 ways: 1) the incidence of healing at a defined point (eg, 12 or 26 weeks), and 2) the total number of open ulcer weeks. The incremental effectiveness was calculated as sNPWT effectiveness minus tNPWT effectiveness.

The analysis described, using point values of all the model inputs, is known as the base case analysis. Further analyses were subsequently performed to investigate the sensitivity of the model to the input parameters and to develop an understanding of the uncertainty in the results. The base case analysis included results at 12 weeks (the timescale of the study by Kirsner et al¹⁹⁾ and extended to 26 weeks.

One-way sensitivity analysis. In any modelling approach, the values used for the model parameters, such as the various probabilities and unit costs, are subject to uncertainty. In order to examine the effects of this uncertainty, sensitivity analyses have become an essential part of economic evaluation. The simplest way to perform this analysis is to test the effect of the input parameters one by one (“one-way sensitivity analysis”).

Following the development of probabilistic methods, one-way analysis may be perceived to be less relevant. However, it can offer an insight into the relative sensitivity of the results to the model inputs. Setting the limits of each variable to a defined percentage of the point value allows the sensitivity to be easily compared across the variables. Therefore, in this study, each input value was changed by ±20%, one input at a time, while keeping all the other inputs constant.

Scenario analyses. Additional scenario analyses also were included as follows:
1)    a 26-week time horizon where, instead of continuing with NPWT, any ulcers remaining unhealed at 12 weeks were changed to standard dressings;
2)    a 26-week time horizon where, instead of continuing with NPWT, any ulcers remaining unhealed at 4 weeks were changed to standard dressings; and
3)    as the base case but with the daily costs of tNPWT and sNPWT equal at the daily cost of sNPWT ($62.36).
 

Scenarios 1 and 2 require a weekly cost of treatment with standard dressings to be assigned to the closed ulcer health state for any weeks after the switch to standard dressings. Nherera et al²⁵ conducted an economic evaluation to compare the use of standard care (including compression, debridement, and foam dressings) with cadexomer iodine with standard care alone for the management of chronic VLUs. This analysis estimated the weekly cost of standard wound care for VLUs from the US payer’s perspective to be $238 (2014 prices). The current authors used this as an estimate of the weekly treatment cost of lower extremity ulcers (VLUs and DFUs) using standard dressings, inflating the cost to 2018 prices using US Bureau of Labor Statistics²⁴ data to result in a weekly cost of $265.02, which was used for the first 2 scenarios. These scenarios also required a weekly transition probability from open ulcer to closed ulcer for standard treatment of hard-to-heal ulcers. In an observational study of 52 hard-to-heal wounds (including VLUs, DFUs and other wound types), Dowsett et al²⁶ estimated that 4 out of 52 of these wounds would heal in a 26-week period. These data were converted to a weekly transition probability of 0.00308 and used in the current first 2 scenarios.

Probabilistic sensitivity analysis. While the one-way sensitivity analysis changes the input values one at a time, a probabilistic approach changes all the values of the model parameters simultaneously according to predetermined distributions. This creates a set of input values that are used to run the model. This process is repeated multiple times with new values of the model parameters being drawn each time in order to create many different scenarios and build up a picture of the uncertainty in the results.
The probabilistic analysis used effectiveness data¹⁹ combined across both studied wound types (DFU and VLU). The relative risk of ulcer closure was drawn from a lognormal distribution, the baseline risk of healing from a beta distribution, and the weekly costs of treatment from gamma distributions. A total of 10 000 iterations of the model were run.

Threshold analysis. A threshold analysis was conducted to estimate the daily cost of treating a wound using tNPWT during which the use of sNPWT was cost-neutral with respect to tNPWT. In this analysis, the daily cost of tNPWT was reduced until the incremental cost became zero.

Data collection. Data were collected into Microsoft Excel spreadsheets for analyses.

Base case analysis. For the treatment of lower-extremity ulcers, sNPWT was found to be cost saving and more effective than tNPWT in the base case for both ulcer types (see Table 2). Based on the assumptions described, switching from tNPWT to sNPWT would result in an expected cost saving of $7756 per patient, an expected reduction of 1.67 open ulcer weeks per patient over 12 weeks, and a reduction of $15 749 and 5.31 open ulcer weeks over 26 weeks. In this situation, where an alternative treatment is both cost-saving and more effective than the current treatment, the alternative treatment is referred to as dominant.

The model also was run for DFUs and VLUs separately (see Table 3). In both cases, sNPWT dominated tNPWT. For DFUs, switching from tNPWT to sNPWT would result in an expected cost saving of $8483 per patient and an expected reduction of 2.32 open ulcer weeks per patient over 12 weeks and a reduction of $18 504 and 7.62 open ulcer weeks over 26 weeks. For VLUs, switching to sNPWT from tNPWT would result in an expected cost saving of $7325 per patient and an expected reduction of 1.29 open ulcer weeks per patient over 12 weeks and a reduction of $14 113 and 3.94 open ulcer weeks over 26 weeks. As a caveat to this analysis, it should be noted that while Kirsner et al¹⁹ found statistically significant differences in proportion healed for all lower extremity ulcers and for DFU alone, the differences in VLU outcomes were not significant.

One-way sensitivity analysis. The one-way sensitivity analysis showed that the model was most sensitive to the daily cost for tNPWT (see Figure 1), with a range of incremental costs from -$11 358 to -$20 140, a finding that was addressed in the scenario and threshold analyses. sNPWT remained dominant (more effective and cost-saving) across the analysis. This indicates that the dominance result is robust to changes in the values of the input variables.  

Scenario analysis. Table 4 shows the results of the 3 scenario analyses. Assuming that ulcers unhealed at 12 weeks would be switched to standard wound care, switching from tNPWT to sNPWT would result in an expected cost saving of $7976 per patient and an expected reduction of 4.42 open ulcer weeks per patient over 26 weeks. Where ulcers unhealed at 4 weeks reverted to standard wound care, switching to sNPWT from tNPWT would result in an expected cost saving of $2536 per patient and an expected reduction of 2.12 open ulcer weeks per patient over 26 weeks. With equivalent daily costs of tNPWT and sNPWT at $62.36 (the daily cost of sNPWT), switching from tNPWT to sNPWT would result in an expected cost saving of $2453 per patient and an expected reduction of 5.31 open ulcer weeks per patient over 26 weeks. In each case, sNPWT remained dominant over tNPWT. Of particular interest is scenario 3. The one-way sensitivity analysis demonstrated that the incremental cost is particularly sensitive to the daily cost of tNPWT. However, sNPWT remains dominant even if the costs of tNPWT and sNPWT are equal.

Probabilistic sensitivity analysis. Table 5 shows the results of the probabilistic sensitivity analysis. At 12 weeks, the expected value of incremental cost showed a savings of $7834, and the expected incremental effectiveness was 1.83 ulcer weeks avoided. At 26 weeks, the expected value of incremental cost showed a cost saving of $15 819, and the expected incremental effectiveness was 5.44 open ulcer weeks avoided. Among all the simulations, 99.8% resulted in sNPWT dominating tNPWT (see Figure 2).

Threshold analysis. The threshold analysis indicated that over 26 weeks, the use of sNPWT breaks even on cost (ie, is cost-neutral, where the incremental cost is zero) when the daily tNPWT treatment cost is set to $44.70 (approximately $17 less than the daily cost for sNPWT). Above this value, with all other inputs unchanged, sNPWT was expected to be cost-saving compared with tNPWT.

sNPWT has been shown to be effective for the treatment of VLUs and DFUs.^18,19 Initially, a case series of mixed etiology wounds treated with sNPWT was compared with retrospective data from tNPWT patients, and closing rates were found to be similar.¹⁸ More recently, a 161-patient RCT demonstrated a higher rate of wound area reduction for sNPWT than for tNPWT.¹⁹ Additionally, an observational study of 52 stalled wounds (>6 weeks duration with area reduction <10% per week in the preceding 4 weeks) by Dowsett et al²⁶ reported that the implementation of a sNPWT pathway resulted in a statistically significant improvement in the closing trajectory, with wound area decreasing an average of 9.6% more per week compared with the previous rate (P = .001). Modelling of the results compared with projected closing rates for the 52 wounds demonstrated a 33.1% cost reduction.²⁶ Cost minimization analyses in the US also have demonstrated cost savings of $1937 per episode of care for sNPWT compared with tNPWT using Medicare claims data and $1586 per episode of care using cost data from long-term care facilities.^22,27  

The current economic evaluation demonstrated cost savings and improved clinical outcomes in favor of sNPWT. Using sNPWT instead of tNPWT would result in an expected cost saving of $7756 per patient and an expected reduction of 1.67 open ulcer weeks per patient over 12 weeks and a reduction of $15 749 and 5.31 open ulcer weeks over 26 weeks. This dominance of sNPWT over tNPWT is a result of 2 main drivers: the higher daily cost of tNPWT compared with sNPWT and the greater incidence of healing with sNPWT. Kirsner et al¹⁹ suggested certain characteristics of the sNPWT dressing may influence the latter and that further research into the mechanism of action of different NPWT systems is needed to understand the observed differences in outcomes.

Based on their finding of the substantial differential daily cost, Delhougne et al²² suggested that a potential cost savings of more than $1 billion over a 10-year period could be realized by the US health system through the increased adoption of sNPWT instead of tNPWT where clinically appropriate. In their cost-minimization analysis,²² the ratio of the tNPWT episode cost to that for sNPWT was approximately 2.2:3 for a range of scenarios and subsets of the data, which included analysis by wound type (including surgical wounds, open wounds, and skin ulcers). Therapy cost per week is likely to be highly dependent on the therapy used, as has been demonstrated in studies such as Carter et al,2⁸ where estimated weekly cycle costs of approximately $500 to more than $2000 were noted when using the products as adjuncts to standard care.

Because the difference in daily cost between tNPWT and sNPWT is a key driver of the incremental cost in the current evaluation (as shown in the results of the one-way sensitivity analysis), a scenario analysis was performed in which the daily costs for sNPWT and tNPWT were equivalent. The results showed sNPWT remained economically dominant because of the difference in the incidence of healing, reducing the average duration of treatment required for sNPWT compared with tNPWT.^8,19 Consequently, it is interesting to consider the effect of equivalent effectiveness of the 2 alternative treatments. If the proportion healed using sNPWT was reduced to that of tNPWT, switching from tNPWT to sNPWT would result in an expected cost saving of $7026 per patient over 12 weeks and an expected reduction of $13 296 over 26 weeks.

As part of the sensitivity analyses, the effect of a shorter duration of NPWT treatment also was investigated. In these 2 scenarios, ulcers unhealed at 4 or 12 weeks, respectively, were switched to standard wound care. This was an attempt to recognize that the duration of NPWT use may vary considerably and that a proportion of ulcers may not respond to treatment.^19,26 Under these assumptions, sNPWT remained economically dominant over tNPWT, suggesting this conclusion may remain valid over a variety of different treatment pathways.

In addition to the 2 cost drivers discussed, sNPWT may have additional advantages over tNPWT not evaluated in the current study. For example, Hurd et al¹⁸ suggested that dressing change time may be shorter for sNPWT and comparable to traditional dressings and that the portable nature of the system may allow patients greater mobility. Kirsner et al¹⁹ used a patient satisfaction questionnaire to compare sNPWT with tNPWT and found a significant trend in favor of sNPWT, suggesting sNPWT may provide additional patient benefits over tNPWT.

This evaluation has several limitations. First, the assumptions made for effectiveness reflect data from only 1 RCT. Second, the weekly costs of both treatments are from 1 cost-minimization analysis, albeit using data from a large number of patients. The authors attempted to address these limitations by performing sensitivity analyses. However, as further clinical and cost studies emerge, updated economic evaluations should be conducted. Real-world observational studies reporting both clinical and economic data would be particularly useful. Finally, this evaluation takes the payer perspective; evaluations from different stakeholder perspectives also may be important, including cost-effectiveness from the home health perspective.

A decision-analytic model was used to determine the cost-effectiveness of sNPWT compared with tNPWT for the treatment of VLUs and DFUs from the US payer (Medicare) perspective. The study results indicated that using sNPWT for lower extremity ulcers is likely to be cost-effective compared with tNPWT. Using sNPWT instead of tNPWT resulted in an expected cost saving of $7756 per patient, an expected reduction of 1.67 open ulcer weeks per patient over 12 weeks, and a reduction of $15 749 and 5.31 open ulcer weeks over 26 weeks. One-way, scenario, and probabilistic sensitivity analyses demonstrated that sNPWT was economically dominant over a range of values of model inputs and scenarios. Threshold analysis showed that even if the daily cost of tNPWT were 71.7% lower than assumed in the model base case, the use of sNPWT would still break even on cost. These results suggest that, where appropriate, sNPWT should be considered as a cost-effective alternative to tNPWT and may provide an opportunity for policy-makers to reduce the economic burden of lower extremity ulcers.

Dr. Kirsner is Chair and Harvey Blank Professor, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Hospital and Clinics Wound Center, University of Miami Miller School of Medicine, Miami, Florida. Mr. Delhougne is a Senior Director, Health Economics & Market Access, Smith & Nephew, Inc, Fort Worth, Texas. Dr. Searle is a Director, HEOR, Smith & Nephew Medical Ltd, Hull, United Kingdom. Please address correspondence to: Richard J Searle, PhD, Smith & Nephew Medical Ltd, 101 Hessle Road, Hull, UK; email: richard.searle@smith-nephew.com.

Gary Delhougne and Dr. Searle are employees of Smith & Nephew.