Abstract
The objective of this study was to assess the cost‐effectiveness of Polyheal compared with surgery in treating chronic wounds with exposed bones and/or tendons (EB&T) due to trauma in France, Germany and the UK, from the perspective of the payers. Decision models were constructed depicting the management of chronic wounds with EB&T and spanned the period up to healing or up to 1 year. The models considered the decision by a plastic surgeon to treat these wounds with Polyheal or surgery and was used to estimate the relative cost‐effectiveness of Polyheal at 2010/2011 prices. Using Polyheal instead of surgery is expected to increase the probability of healing from 0·93 to 0·98 and lead to a total health‐care cost of €7984, €7517 and €8860 per patient in France, Germany and the UK, respectively. Management with surgery is expected to lead to a total health‐care cost of €12 300, €18 137 and €11 330 per patient in France, Germany and the UK, respectively. Hence, initial treatment with Polyheal instead of surgery is expected to lead to a 5% improvement in the probability of healing and a substantial decrease in health‐care costs of 35%, 59% and 22% in France, Germany and the UK, respectively. Within the models' limitations, Polyheal potentially affords the public health‐care system in France, Germany and the UK a cost‐effective treatment for chronic wounds with EB&T due to trauma, when compared with surgery. However, this will be dependent on Polyheal's healing rate in clinical practice when it becomes routinely available.
Keywords: Chronic wound, Cost‐effectiveness, Flap, France, Germany, Polyheal, Skin graft, UK
Introduction
Chronic wounds with exposed bones and/or tendons (EB&T) are generally managed surgically by plastic surgeons. Patients with a large chronic wound with EB&T generally undergo a flap procedure 1, whereas a skin graft might be performed on smaller wounds or when patients are too debilitated to undergo a flap procedure 1. Healing is critical as failure of the wound to heal is associated with a risk of infection, tissue necrosis and progressive loss of soft tissue and skin 2. Moreover, patients with hard‐to‐heal wounds may experience severe distress as a result of a reduction in their quality of life 3.
Polyheal comprises non biodegradable, chemically inert, synthetic, negatively charged 5‐micron polystyrene microspheres suspended in a nutrient medium. It has been postulated that these microspheres exert a therapeutic effect on wounds by providing a supportive, healing microenvironment on the wound surface by serving as an additional surface for the attachment and migration of epithelial, endothelial and inflammatory cells 4, 5. Negatively charged microspheres have been shown to increase the secretion of growth factors, such as growth factor‐beta 1, which stimulates bone repair in rabbits 6. Additionally, Polyheal adsorbs to its surface excess proteolytic enzymes, such as matrix metalloproteinases and human neutrophil elastase, that appear to prevent normal healing. Polyheal has been developed as a single use agent which can be applied topically to a wound, including chronic wounds with EB&T.
The clinical evidence supporting use of Polyheal in the treatment of chronic wounds with EB&T comes from three separate studies. One of the studies was a prospective, double‐blind, randomised, multi‐centre study in which Polyheal was compared with saline in the treatment of chronic wounds with EB&T due to trauma with different aetiologies. The other two studies were open label, observational studies on the use of Polyheal in chronic wounds with EB&T due to different aetiologies 7, 8, 9, 10.
All three studies recruited patients who were ≥18 years of age with a chronic wound, defined as a wound that had not healed for at least 4 weeks prior to starting treatment with Polyheal. Subjects were eligible to participate in one of the studies if the edges of their target lesion area were between 2 and 200 cm2 at baseline. In the double‐blind study, patients were randomised to receive either Polyheal or saline for 4 weeks twice daily, followed by treatment on an outpatient basis according to the investigator's recommendation for an additional 8 weeks (which excluded the use of Polyheal or saline). Patients who completed the first 12‐week period (including 8 weeks of follow‐up) were subsequently followed‐up and evaluated at 6, 12 and 24 months. In the open label studies, patients were treated with Polyheal twice daily for a mean of 4 weeks followed by standard support care specific to their wound type for as long as required 7, 8, 9, 10. These studies demonstrated that Polyheal affords an effective alternative treatment to surgery for chronic wounds with EB&T due to traumatic injuries. Against this background, the aim of this study was to assess the cost‐effectiveness of Polyheal compared with surgery in managing chronic wounds with EB&T due to trauma in France, Germany and the UK.
Methods
Economic models
Three decision models were constructed depicting the management of chronic wounds with EB&T due to trauma with either Polyheal or surgery; one each for France, Germany and the UK (Figure 1). The models were based on published clinical outcomes pertaining to the surgical procedures, predicted healing rates with Polyheal derived from the aforementioned clinical studies and patient pathways and associated health‐care resource use derived from interviews with six clinicians in each country. The period of the models was up to healing or 1 year for unhealed wounds, and the analysis was performed from the payers' perspective.
Figure 1.
Decision model depicting the management of chronic wounds with exposed bones and/or tendons (EB&T). Numbers denote the probability of a patient following a particular path. Three sets of numbers denote the probability in France, Germany and the UK, respectively.
Model inputs
Resource use
There was a lack of published evidence pertaining to the management of chronic wounds with EB&T in each of the countries. Additionally, none of the clinical studies collected resource utilisation associated with use of Polyheal. Hence, the authors obtained this missing information by interviewing six consultants in each country who treated chronic wounds with EB&T due to trauma. The interviews were based on a structured questionnaire and focused on patient management, treatment patterns and resource utilisation. Information provided by the interviewees was based on their clinical experience and scrutiny of their patients' records to verify and validate their estimates.
Current management of chronic wounds with EB&T due to trauma in France
Each plastic surgeon interviewed saw a mean of 40 patients with chronic wounds with EB&T due to trauma per annum. Moreover, each clinician saw approximately seven new patients with chronic wounds with EB&T due to trauma per annum.
According to the interviewees, the management of these wounds is very individual and influenced by patient's status, previous treatments, wound aetiology, wound location and size. Nevertheless, during the first consultation with a plastic surgeon, patients usually undergo a clinical/physical examination and the aetiology of the wound is determined. The wound site is examined for infection and necrosis. Generally, no medical procedures or tests will be performed at this stage. Patients have approximately two consultations with a plastic surgeon before the start of any treatment.
According to the interviewees, 67% of patients receive a flap procedure (free, regional or pedicle) and 33% receive a skin graft. The time to initiating a surgical procedure depends on urgency and ranged from 1 week to several months. During this time, patients have their wound dressed three times a week at home by a nurse using a range of dressings.
The majority of patients is hospitalised before surgery for a mean of 2 days if they were not already hospitalised for their underlying condition. The wound site is usually prepared for surgery and patients undergo a range of pre‐surgical tests. In addition to the use of dressings, 10% of patients receive negative‐pressure wound therapy (NPWT) before surgery. These patients are hospitalised for a mean of 8 days before their surgical procedure.
Post‐surgery, patients who received a flap procedure are more likely to be admitted to an intensive care unit (ICU) for up to 7 days depending on the complexity of the procedure and patients' comorbidities. Patients are then transferred to a general ward for 2–3 weeks. Patients who received a skin graft generally go directly to a general ward for 3–21 days.
Following surgery, the wound is treated with one of several dressings, such as an alginate. Usually this is not changed until it falls off. Later, the dressings used depend on the wound characteristics, but are generally a mix of vaseline gauze, paraffin gauze, non adherent interface dressings and hydrocellular dressings. The wound is treated with dressings until healing.
The model assumes that for a healing wound dressings would be changed: six times in the first week, three times in the second and third week, twice a week in the fourth and fifth week and once in the sixth week. For a non healing wound the model assumes dressings would be changed six times in the first week and three times until the ninth week after which patients would undergo another surgical procedure. Patients who continue treatment with dressings post‐discharge have their dressings changed at home by nurses. Plastic surgeons review the patients at 7, 15 and 30 days post‐discharge when the dressings are also changed. Patients also see a physiotherapist twice a week and psychologist once a week until healing and up to 8 weeks for those wounds that remain unhealed.
According to the interviewees, 50% of patients who have a failure of their initial flap undergo a second flap procedure, 35% undergo a skin graft, 10% are treated conservatively using dressings and 5% undergo an amputation. Similarly, 80% of patients who have a failure of their initial skin graft undergo a second skin graft, 19% are treated conservatively using dressings and 1% undergo an amputation.
Patients whose wounds remained unhealed following surgery are treated with dressings and are typically managed in an outpatient setting. According to the interviewees, these patients are seen by a plastic surgeon once every 2 weeks. The model assumes that these patients would continue treatment with dressings for up to 1 year and the dressings would be changed three times per week until healing. The model further assumes that a mix of dressings would be used including hydrocolloid dressings, non adherent interface dressings and polyurethane dressings, and that there would be no complications associated with these dressings.
Current management of chronic wounds with EB&T due to trauma in Germany
Each plastic surgeon interviewed saw a mean of 10 patients with chronic wounds with EB&T due to trauma per annum. Moreover, each clinician saw approximately five new patients with chronic wounds with EB&T due to trauma per annum.
The management of chronic wounds with EB&T due to trauma in Germany was similar to that in France. However, all patients undergo a flap procedure. While waiting for surgery, patients continue with their previous wound management care plan.
As in France, all patients are hospitalised in a plastic surgery ward for a mean of 2 days before surgery, during which the wound site is prepared. Eight percent of patients receive NPWT before debridement and 51% of patients receive NPWT after debridement. Patients undergoing NPWT are hospitalised for a mean of 7 days before the surgical procedure.
Post‐surgery, most patients are transferred to a general ward; only those with an aggravated underlying condition are transferred to an ICU. Post‐surgery, patients stay on the general ward for approximately 3 weeks and be treated with a range of dressings depending on the wound's characteristics. The model assumes a mix of: silver alginate dressings (10% of patients), enzymatic ointments (20% of patients), non stretch gauze (20% of patients), hydrocolloid dressings (35% of patients), hydropolymer adhesive dressings (35% of patients) and sterile compresses (20% of patients).
The frequency of dressing change and clinician visits was similar to that in France. Patients who continue treatment with dressings post‐discharge have their dressings changed at home by a home nurse service.
According to the interviewees, 85% of patients who have a failure of their initial flap undergo a second flap procedure, 10% are treated conservatively using dressings and 5% undergo an amputation. Patients whose wounds remain unhealed following surgery are generally managed similar to those in France.
Current management of chronic wounds with EB&T due to trauma in the UK
Each plastic surgeon interviewed saw a mean of 35 patients with chronic wounds with EB&T due to trauma per annum. Moreover, each clinician saw approximately seven new patients with chronic wounds with EB&T due to trauma per annum.
The management of chronic wounds with EB&T due to trauma in the UK was similar to that in France and Germany. However, according to the interviewees, 90% of patients undergo a flap procedure and the other 10% receive a skin graft. The time to initiating a surgical procedure depends on urgency and ranged from 1 week to several months. During this time, 90% and 10% of patients have their wound dressed with a range of dressings three times a week by a nurse in an outpatient clinic and at home, respectively.
The majority of patients are hospitalised before surgery for a mean of 2 days if they were not already hospitalised for their underlying condition. In addition to the use of dressings, 40% of patients receive NPWT before surgery in an outpatient setting.
Post‐surgery, patients who received a flap procedure are more likely to be admitted to an ICU for up to 7 days depending on the complexity of the procedure and patients' comorbidities. Patients are then transferred to a general ward for 5–28 days. Patients who receive a skin graft typically go directly to a general ward for a mean of 5 days. The duration of stay in the ward depends on the complexity of the reconstruction. Following surgery, the wound is treated with one of several dressings, such as paraffin gauze (50% of patients) or a semi‐permeable adhesive (50% of patients) and the donor site is dressed with a dressing such as a non woven synthetic adhesive. Following a skin graft, the wound is dressed with a dressing such as paraffin gauze.
Following discharge patients are followed‐up in the plastic surgery clinic by nurses. Patients have a mean of three dressing changes post‐discharge. Patients who received a flap procedure have four consultations with a plastic surgeon post‐discharge at 4, 8, 12 and 24 weeks. Patients who received a skin graft are seen less frequently, with a plastic surgeon consultation at 1 and 9 weeks post‐discharge. Approximately 85% of patients also see a physiotherapist twice a week for 2–4 months.
According to the interviewees, 80% of patients who have a failure of their initial flap undergo a second flap procedure, 5% undergo a skin graft and 15% are treated conservatively using dressings. Following failure of the first flap procedure, 67% of patients are managed with a dressing such as paraffin gauze (50%) or NPWT (50%) for a month in an outpatient clinic to improve granulation before undergoing another surgical procedure. Approximately 90% of patients who have a failure of their initial skin graft are initially treated conservatively using dressings and 10% undergo NPWT after which 75% of patients receive a second skin graft and 25% a flap procedure.
Patients whose wounds remain unhealed following surgery are treated conservatively with dressings and are typically managed in an outpatient setting. According to the interviewees, these patients are reviewed by a plastic surgeon every 1–2 months. The model assumes that these patients would continue treatment with dressings for up to 1 year and the dressings would be changed three times per week until healing in the plastic surgery clinics (90% of patients) or in a patients' home (10% of patients). The model assumes a mix of dressings would be used including paraffin gauze, soft silicone and a semi‐permeable adhesive and that there would be no complications associated with these dressings.
Management of chronic wounds with EB&T due to trauma with Polyheal
Health‐care resource utilisation associated with the use of Polyheal was not collected in any of the aforementioned studies 7, 8, 9, 10. Consequently, this was estimated from the interviewees in each of the three countries.
According to the interviewees, patients would undergo the following tests and procedures before starting treatment with Polyheal: Doppler ultrasound scan (75% of patients), routine lab tests (100% of patients) and X‐rays (20% of patients). The model assumes that Polyheal would be administered twice a day for 28 days and that patients would be hospitalised at the start of Polyheal treatment for 3 days in France and Germany, but not in the UK. After discharge, Polyheal would be administered twice a day at a patient's home: once a day by a carer and once a day by a nurse. The top dressing (gauze) would require changing once a day. During the 4‐week Polyheal treatment phase, patients would make weekly outpatient visits to see the plastic surgeon.
The model further assumes that after Polyheal treatment patients would be managed with conventional dressings. In accordance with clinical practice, patients' dressings were assumed to be changed at their home by nurses in France and Germany. However, in the UK, patients' dressings are changed in the outpatient clinic (90% of patients) and at home (10% of patients) by a nurse.
For wounds that heal during the month of Polyheal treatment, the model assumes that patients would undergo two dressing changes during the first 2 weeks after Polyheal treatment and one further dressing change in the third week. For wounds that heal after the month of Polyheal treatment, the model assumes that patients would undergo three dressing changes per week until the onset of healing followed by two dressing changes per week for 2 weeks followed by one more dressing change. For wounds that do not heal during the 5 months after stopping Polyheal treatment, the model assumes that patients would undergo three dressing changes per week for 5 months after which patients would undergo surgery in accordance with the practice of the relevant country (i.e. 67% would underg a flap procedure and 33% a skin graft in France; 100% would undergo a flap procedure in Germany; 90% would undergo a flap procedure and 10% a skin graft in the UK).
The model also assumes that Polyheal‐treated patients would have three outpatient visits to a plastic surgeon if the wound heals within the first 2 months of the start of Polyheal treatment. Those patients whose wound does not heal within the first 2 months of the start of Polyheal treatment would have three outpatient visits to a plastic surgeon during the first 2 months plus one additional visit each month until the wound heals. Moreover, the model assumes that Polyheal‐treated patients would not see a physiotherapist or a psychologist unless the wound does not heal and they then undergo surgery.
Clinical outcomes
The clinical basis of the models was published clinical outcomes together with the aforementioned clinical studies of Polyheal.
Surgical outcomes
A systematic literature review was performed using Medline to estimate clinical outcomes associated with managing chronic wounds with EB&T with a flap procedure or skin graft. The search terms included: auto‐graft; chronic wound; exposed bone and/or tendon; fracture; free/pedicle/rotational/muscle flap procedure; split/full thickness skin graft; trauma with exposed bone and/or tendon and traumatic wound. The review assessed studies published between 1982 and 2011 and included English, Czech, Italian and German language publications. The review included case reports, clinical reviews, multi‐centre trials, single‐centre reports, observational studies, prospective and retrospective studies. Publications that reported outcomes for mixed wounds were excluded from the analysis. Where more than one publication was available, the mean efficacy rates were weighted according to the sample size in each study.
The review identified: five publications reporting the success rate of a first flap procedure in a total of 153 wounds 11, 12, 13, 14, 15; five reporting the success of a second flap procedure following the failure of a first flap in a total of 140 wounds 13, 16, 17, 18, 19; two reporting the success rate of a skin graft following an initial flap procedure in a total of 38 wounds 20, 21 and two reporting the success rate of an initial skin graft in a total of 27 wounds 22, 23. However, publications reporting the success rates associated with a skin graft followed by either (1) a second skin graft or (2) a flap procedure could not be identified. Hence, the analysis assumed the success rate would be comparable with either that of a second flap procedure at 70% or a skin graft followed by a flap procedure at 67%. The validity of this assumption was tested using extensive sensitivity analysis. The success rates that have been incorporated into the decision models are summarised in Table 1.
Table 1.
Success rates associated with surgical procedures used in the management of chronic wounds with exposed bones and/or tendons (EB&T)
| Procedure | No of publications | No of evaluable wounds | Success of first procedure | Success of second procedure |
|---|---|---|---|---|
| Flap procedure 11, 12, 13, 14, 15 | 5 | 153 | 85% | – |
| Flap followed by another flap procedure 13, 16, 17, 18, 19 | 5 | 140 | 81% | 70% |
| Flap followed by skin graft 20, 21 | 2 | 38 | 89% | 67% |
| Skin graft 22, 23 | 2 | 27 | 85% | – |
From the published literature it was also estimated that a mean 82% of patients undergo an amputation after the failure of second‐line surgery 11, 12, 13, 15, 16, 20. This was based on the publications reporting amputation rates irrespective of the prior surgical procedure.
The systematic literature review was used to estimate the rate of post‐surgical complications. Twelve publications with a total of 304 wounds reported the rate of post‐flap procedure complications. These included arterial inflow, haematoma, necrosis, infection and wound dehiscence. Wound infection was estimated to occur in 7% of wounds, whereas the incidence of the other complications was <0·05 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23. Hence, they have been excluded from our analysis. The authors could not identify any publications reporting post‐graft complications in chronic wounds with EB&T. Consequently, the rate of post‐graft complications was assumed to be the same as that in patients who undergo a flap procedure.
Polyheal's outcomes
The sample size in each of the three studies was relatively small. Hence, the patients were pooled to form one data set comprising 29 chronic wounds with EB&T of various aetiologies that were treated with Polyheal twice‐daily for a mean of 4 weeks. Patients' mean age at the start of the study was 65·4 ± 16·6 years and 48% of the cohort were female. Moreover, patients had their wound for a mean 2·9 ± 4·0 months at the time of study entry and the wound size at the time of study entry was 27·3 ± 33·1 cm2.
After 4 weeks' treatment there was a significant improvement in granulation and coverage of the exposed structures and wounds. Time‐series forecasting was undertaken on the Polyheal trial data sets to extrapolate each patient's wound size to 12 months using moving averages. The resulting predicted complete closure rates (i.e. healing rates) were incorporated into the models and are summarised in Figure 2. The analysis showed that approximately 79% of chronic wounds with EB&T are expected to heal by 6 months, with a mean time to healing of 3 months. The analysis also showed that wounds that remain unhealed by 5 months were unlikely to heal with Polyheal. There were no reports of any significant treatment‐related complications, and no patients required a reconstructive treatment following successful wound closure with Polyheal.
Figure 2.
Expected healing associated with Polyheal.
Model outputs
The models were used to estimate the expected probability of being healed at 1 year following the start of Polyheal treatment or surgery in accordance with current clinical practice. National unit resource costs at 2010/2011 prices obtained from published sources in each of the countries 24, 25, 26, 27, 28, 29, 30, and where unavailable from the interviewees, (Table 2) were applied to the resource use estimates in the models to estimate the health‐care cost of a patient being initially treated with Polyheal or a surgical procedure. The cost‐effectiveness of managing patients with Polyheal compared with surgery was calculated as the difference between the expected costs of the two treatment strategies over 1 year, divided by the difference between the expected probabilities of being healed at 1 year. The relative cost‐effectiveness of Polyheal was defined as the cost per additional healed patient. If a treatment resulted in an improved outcome for less cost it was defined as a ‘dominant treatment’.
Table 2.
Unit resource costs in Euros at 2010/2011 prices. Unit costs from the UK were converted from Sterling to Euros using an exchange rate of £1 = €1·1
| Resource | Unit costs (€ at 2010/2011 prices) in: | ||
|---|---|---|---|
| France | Germany | UK | |
| Alginate dressing | €10 | ||
| Amputation | €6853 | €5300 | €9456 |
| Antibiotics (per course) | €150 | €34 | |
| Biopsy | €219 | €30 | €196 |
| Computerised tomography scan | €25 | €78 | €110 |
| Doppler ultrasound scan | €138 | €27 | €61 |
| Electrocardiogram | €32 | €35 | |
| Electrocardiography | €10 | ||
| Flap procedure | €8321 | €10 206 | €6488 |
| General ward stay (per night) | €257 | €396 | €265 |
| Home nurse visit | €50 | €10 | €80 |
| Hospital nurse visit | €13 | €11 | €45 |
| Hydrocellular dressing | €4 | ||
| Hydrocolloid dressing | €4 | €8 | |
| Intensive care unit stay (per night) | €1365 | ||
| Iruxol ointment | €34 | ||
| Laboratory tests | €3 | €2 | €3 |
| Magnetic resonance imaging scan | €69 | €98 | €193 |
| Microbiology tests | €9 | ||
| Negative‐pressure wound therapy | €178 | €450 | |
| Negative‐pressure wound therapy (day case) | €656 | ||
| Negative‐pressure wound therapy (inpatients) | €1465 | ||
| Negative‐pressure wound therapy (outpatients) | €303 | ||
| Non woven synthetic adhesive | €3 | ||
| Non adherent interface dressing | €3 | ||
| Paraffin gauze dressing | €4 | €1 | €1 |
| Physiotherapist consultation | €23 | €33 | €37 |
| Plastic surgeon follow‐up consultation | €23 | €25 | €111 |
| Plastic surgeon initial consultation | €43 | €25 | €154 |
| Polyheal (per week's treatment) | €400 | €400 | €400 |
| Polyurethane foam dressing | €1 | €8 | |
| Povidone‐iodine/polyethylene glycol dressing | €1 | ||
| Psychologist consultation | €31 | €41 | €34 |
| Semi‐permeable adhesive dressing | €2 | ||
| Skin graft | €6259 | €4299 | |
| Soft silicone dressing | €4 | ||
| Transcutaneous oxygen measurement | €33 | €33 | €156 |
| Vaseline gauze dressing | €1 | €2 | €1 |
| X‐ray | €20 | €25 | €30 |
Sensitivity analyses
Probabilistic sensitivity analyses were undertaken using Monte‐Carlo simulations (10 000 iterations of the model) by simultaneously varying the probabilities, clinical outcomes, unit costs and resource use values within the models. Probabilities and clinical outcomes were varied randomly according to a beta distribution by assuming a 20% standard distribution around the mean. Unit resource costs were varied randomly according to a gamma distribution and resource use according to a log‐normal distribution by assuming a 20% standard distribution around the mean. These analyses enabled the construction of cost‐effectiveness acceptability curves showing the probability of Polyheal being cost‐effective at different thresholds. Deterministic sensitivity analyses were also performed to assess how the cost‐effectiveness of initially using Polyheal instead of surgery to manage chronic wounds with EB&T changes by varying different assumptions in the model.
Results
Clinical outcomes
Patients who remain unhealed following initial treatment with Polyheal subsequently undergo surgery. Accordingly, the models calculated the expected probability of healing following initial treatment with Polyheal and surgery to be 0·98 (95% CI: 0·95; 0·99) and 0·93 (95% CI: 0·78; 0·99), respectively, in all three countries. Hence, initial treatment with Polyheal instead of surgery is expected to lead to a 5% increase in the probability of healing from 0·93 to 0·98. The expected time to healing following initial treatment with Polyheal was 17 weeks compared with 9 weeks following initial treatment with surgery.
Health‐care resource use and corresponding costs
A patient who is initially managed surgically is expected to undergo a mean of 1·2 surgical procedures. In contrast, a patient who is initially managed with Polyheal is expected to undergo a mean of 0·2 surgical procedures. In France and the UK, a surgeon sees approximately seven new patients with chronic wounds with EB&T per annum, whereas in Germany a surgeon sees approximately five new patients per annum. Hence, initial management with Polyheal instead of surgery to treat all new patients is expected to release surgical theatre time equivalent to five flap procedures and two skin grafts in France and the UK, and five flap procedures in Germany per surgeon per annum.
Initial management of chronic wounds with EB&T with Polyheal is expected to lead to a total health‐care cost of €7984 (95% CI: €6383; €9888) per patient in France, €7517 (95% CI: €5840; €9723) per patient in Germany and €8860 (95% CI: €7322; €10770) per patient in the UK. In contrast, initial management with surgery is expected to lead to a total health‐care cost of €12 300 (95% CI: €9135; €16 678) per patient in France, €18 137 (95% CI: €13 224; €24 988) per patient in Germany and €11 330 (95% CI: €7821; €17 014) per patient in the UK (Table 3). Hence, initial treatment with Polyheal instead of surgery is expected to lead to a 35% cost reduction of €4317 per patient in France, a 59% cost reduction of €10 620 per patient in Germany and a 22% cost reduction of €2470 per patient in the UK.
Table 3.
Expected health‐care costs per patient (€ at 2010/2011 prices), (percentage of total cost is in parentheses)
| Resource | Expected 12‐monthly health‐care costs (€ at 2010/2011 prices) following initial presentation to a plastic surgeon in: | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| France | Germany | UK | ||||||||||
| Surgery group | Polyheal group | Surgery group | Polyheal group | Surgery group | Polyheal group | |||||||
| Polyheal | 0·00 | (0%) | 1600·00 | (20%) | 0·00 | (0%) | 1600·00 | (21%) | 0·00 | (0%) | 1600·00 | (18%) |
| Nurse visits | 1637·04 | (13%) | 2894·55 | (36%) | 136·45 | (1%) | 564·64 | (8%) | 297·33 | (3%) | 3729·59 | (42%) |
| Dressings | 143·11 | (1%) | 275·50 | (3%) | 765·34 | (4%) | 375·23 | (5%) | 341·08 | (3%) | 160·45 | (2%) |
| Surgical procedures and hospitalisations | 8829·77 | (72%) | 2604·82 | (33%) | 12 190·37 | (67%) | 3754·92 | (50%) | 7830·05 | (69%) | 1636·04 | (18%) |
| Surgeon visits | 160·10 | (1%) | 292·99 | (4%) | 149·95 | (1%) | 288·45 | (4%) | 585·10 | (5%) | 1215·93 | (14%) |
| Pre‐surgical tests | 324·59 | (3%) | 66·96 | (1%) | 232·99 | (1%) | 89·67 | (1%) | 460·52 | (4%) | 138·57 | (2%) |
| Negative‐pressure wound therapy | 390·93 | (3%) | 82·21 | (1%) | 3025·80 | (17%) | 632·71 | (8%) | 1080·19 | (10%) | 225·70 | (2%) |
| Physiotherapist visits | 226·16 | (2%) | 47·13 | (<1%) | 185·33 | (1%) | 38·76 | (1%) | 43·24 | (<1%) | 9·03 | (<1%) |
| Psychotherapist visits | 347·31 | (3%) | 70·51 | (1%) | 499·44 | (3%) | 105·21 | (1%) | 0·00 | (0%) | 0·00 | (0%) |
| Post‐surgical complications | 241·43 | (2%) | 49·22 | (1%) | 951·03 | (5%) | 67·64 | (1%) | 692·51 | (6%) | 144·69 | (2%) |
| Total | 12 300·44 | (100%) | 7983·89 | (100%) | 18 136·70 | (100%) | 7517·23 | (100%) | 11 330·02 | (100%) | 8860·00 | (100%) |
In the Polyheal group, nurse visits were the primary cost driver in France and the UK accounting for 36% and 42% of the cost, respectively, whereas surgery and hospitalisation was the primary cost driver in Germany accounting for 50% of the cost. The acquisition cost of Polyheal accounted for 18–21% of the total management cost in the Polyheal group. The cost of surgery and hospitalisation was the primary cost driver in the surgery group, accounting for 72%, 67% and 69% of the total health‐care cost in France, Germany and the UK, respectively. Nurse visits were the secondary cost driver accounting for a further 13% of the cost in France. However, NPWT was the secondary cost driver in Germany and the UK accounting for a further 17% and 10% of the cost, respectively.
Cost‐effectiveness analysis
According to the models, initial treatment with Polyheal instead of surgery is expected to lead to a decrease in health‐care costs (€4317 per patient in France, €10 620 per patient in Germany and €2470 per patient in the UK) and a 5% improvement in the probability of healing. Hence, Polyheal affords the health‐care system in each country a cost‐effective (dominant) treatment for chronic wounds with EB&T due to trauma.
Sensitivity analyses
Probabilistic sensitivity analyses estimated the distribution in the incremental 12 monthly costs and probability of healing at 12 months, from which it can be seen that the majority of the samples are located in the dominant (bottom right) quadrant (Figure 3). These analyses also showed that Polyheal affords a more cost‐effective (dominant) treatment in Germany followed by France and then the UK.
Figure 3.
Scatterplot of the incremental cost‐effectiveness of Polyheal compared with surgery (10 000 iterations of each model).
Cost‐effectiveness acceptability curves were generated from the probabilistic sensitivity analyses (Figure 4). These demonstrated that at a cost‐effectiveness threshold of as low as €1, it is likely that up to 99%, 90% and 85% of a cohort would be cost‐effectively treated with Polyheal in Germany, France and the UK, respectively.
Figure 4.
Cost‐effectiveness acceptability curves.
Deterministic sensitivity analyses (Table 4) were undertaken to identify how the relative cost‐effectiveness of Polyheal changed by varying different parameters in the model. These analyses showed the relative cost‐effectiveness of Polyheal in the UK to be sensitive to:
Polyheal's healing rate.
Number of clinician visits in the Polyheal group.
Probability of receiving a conservative treatment with dressings before surgery.
Table 4.
Sensitivity analyses
| Scenario | France | Germany | UK | |||
|---|---|---|---|---|---|---|
| Base case value | Effect | Base case value | Effect | Base case value | Effect | |
| Probability of having initial surgery with a flap procedure instead of a skin graft ranges from 0 to 1·0 | 0·67 | Polyheal remains dominant | 0·0 | Polyheal remains dominant | 0·90 | Polyheal remains dominant |
| Probability of having a second flap procedure ranges from 0·3 to 1·0 | 0·50 | Polyheal remains dominant | 0·85 | Polyheal remains dominant | 0·80 | Polyheal remains dominant |
| Probability of having a second graft ranges from 0·3 to 1·0 | 0·80 | Polyheal remains dominant | 0·75 | Polyheal remains dominant | ||
| Probability of having a graft after a flap procedure ranges from 0 to 0·7 | 0·35 | Polyheal remains dominant | 0·05 | Polyheal remains dominant | ||
| Probability of having an amputation after a first flap procedure ranges from 0 to 0·20 | 0·05 | Polyheal remains dominant | 0·05 | Polyheal remains dominant | 0·0 | Polyheal remains dominant |
| Probability of having an amputation after a first graft ranges from 0·2 to 0·7 | 0·01 | Polyheal remains dominant | 0·0 | Polyheal remains dominant | ||
| Probability of being treated conservatively with dressings after a first flap procedure ranges from 0·05 to 1·0 | 0·10 | Polyheal remains dominant | 0·10 | Polyheal remains dominant | 0·72 | Polyheal remains dominant |
| Probability of being treated conservatively with dressings after a first graft ranges from 0·1 to 1·0 | 0·19 | Polyheal remains dominant | 1·0 | Polyheal remains dominant | ||
| Probability of having post‐surgical complications is halved and doubled | 1·0 | Polyheal remains dominant | 1·0 | Polyheal remains dominant | 1·0 | Polyheal remains dominant |
| Probability of having NPWT before surgery is halved and doubled | 1·0 | Polyheal remains dominant | 1·0 | Polyheal remains dominant | 1·0 | Polyheal remains dominant |
| Probability of healing after a first flap procedure ranges from 0·4 to 1·0 | 0·85 | Polyheal remains dominant | 0·85 | Polyheal remains dominant | 0·85 | Polyheal remains dominant |
| Probability of healing after a second flap procedure ranges from 0·3 to 1·0 | 0·70 | Polyheal remains dominant | 0·70 | Polyheal remains dominant | 0·70 | Polyheal remains dominant |
| Probability of healing after a first graft ranges from 0·4 to 1·0 | 0·85 | Polyheal remains dominant | 0·85 | Polyheal remains dominant | ||
| Probability of healing after a second graft ranges from 0·3 to 1·0 | 0·70 | Polyheal remains dominant | 0·70 | Polyheal remains dominant | ||
| Probability of healing following a graft after a flap procedure ranges from 0·3 to 1·0 | 0·67 | Polyheal remains dominant | 0·67 | Polyheal remains dominant | ||
| Probability of healing following a flap procedure after a graft ranges from 0·3 to 1·0 | 0·0 | Polyheal remains dominant | 0·67 | Polyheal remains dominant | ||
| Probability of healing with Polyheal ranges from 0·4 to 1·0 | 0·79 | Polyheal remains dominant | 0·79 | Polyheal remains dominant | 0·79 | Polyheal's cost‐effectiveness ranges from €18 000 to being dominant, breaking even at 0·50 |
| Number of clinician visits in the surgery group is halved and doubled | 1·0 | Polyheal remains dominant | 1·0 | Polyheal remains dominant | 1·0 | Polyheal remains dominant |
| Number of clinician visits in the Polyheal group is halved and doubled | 1·0 | Polyheal remains dominant | 1·0 | Polyheal remains dominant | 1·0 | Polyheal's cost‐effectiveness ranges from dominant to €50 000, breaking even at 1·50 |
| Number of home nurse visits for administering Polyheal ranges from twice a day to once every 4 days | Once a day | Polyheal remains dominant | Once a day | Polyheal remains dominant | Once a day | Polyheal remains dominant |
| Daily number of dressing changes is halved and doubled | 1·0 | Polyheal remains dominant | 1·0 | Polyheal remains dominant | 1·0 | Polyheal remains dominant |
| Length of hospital admission to initiate Polyheal treatment ranges from 0 to 5 days | 3·0 | Polyheal remains dominant | 3·0 | Polyheal remains dominant | 0·0 | Polyheal remains dominant |
| Cost of a home nurse visit ranges from €5 to €100 | €50 | Polyheal remains dominant | €10·9 | Polyheal remains dominant | €80 | Polyheal remains dominant |
| Cost of a hospital nurse visit ranges from €20 to €90 | €45 | Polyheal remains dominant | ||||
| Cost of a follow‐up visit to a surgeon ranges from €20 to €200 | €23 | Polyheal remains dominant | €25 | Polyheal remains dominant | €111 | Polyheal remains dominant |
| Cost of a first flap procedure ranges from €4000 to €10 000 | €8321 | Polyheal remains dominant | €10 206 | Polyheal remains dominant | €6488 | Polyheal remains dominant |
| Cost of a first graft ranges from €3000 to €9000 | €6259 | Polyheal remains dominant | €4299 | Polyheal remains dominant | ||
| Cost of a second flap procedure ranges from €4000 to €10 000 | €8321 | Polyheal remains dominant | €10 206 | Polyheal remains dominant | €6488 | Polyheal remains dominant |
| Cost of a second graft ranges from €3000 to €9000 | €6259 | Polyheal remains dominant | €4299 | Polyheal remains dominant | ||
| Cost of an amputation ranges from €3000 to €10 000 | €6853 | Polyheal remains dominant | €5300 | Polyheal remains dominant | €8596 | Polyheal remains dominant |
| Acquisition cost of Polyheal ranges from €50 to €75 per vial | €71 | Polyheal remains dominant | €71 | Polyheal remains dominant | €71 | Polyheal remains dominant |
| Probability of being conservatively treated with dressing first‐line instead of surgery ranges from 0 to 1·0 | 0·0 | Polyheal's cost‐effectiveness ranges from dominant to €2000, breaking even at 0·70 | 0·0 | Polyheal's cost‐effectiveness ranges from dominant to €100, breaking even at 0·95 | 0·0 | Polyheal's cost‐effectiveness ranges from dominant to €200, breaking even at 0·90 |
NPWT, negative‐pressure wound therapy.
The relative cost‐effectiveness of Polyheal in France and Germany was only sensitive to the probability of receiving conservative treatment with dressings before surgery. Polyheal's cost‐effectiveness compared with surgery was minimally sensitive to changes in other model inputs in any of the countries.
Discussion
To our knowledge this is the first health economic study assessing the cost‐effectiveness of using Polyheal to manage chronic wounds with EB&T. The authors could not identify any other health economic studies in the management of chronic wounds with EB&T. However, we have previously estimated the cost‐effectiveness of using Polyheal plus compression bandaging to treat chronic venous leg ulcers of >6 months duration and found it to be a cost‐effective treatment strategy when compared with compression bandaging alone 31. This study aimed to determine the cost‐effectiveness of using Polyheal compared with the current practice of employing surgery to manage chronic wounds with EB&T due to trauma. Polyheal is still being developed as a treatment modality for this wound type, with the only assessment of its efficacy in these wounds being the three aforementioned clinical studies 7, 8, 9, 10 which were used as the clinical basis for constructing the decision models.
All the patients in the three Polyheal studies had wounds with EB&T, however, with varying aetiologies. Hence, the models may not necessarily reflect clinical outcomes associated with a cohort of patients with chronic wounds with EB&T due to trauma. Nevertheless, the healing rates were found to be comparable across patients in the dataset. Also, the patients in the three studies were followed‐up at different times, with some patients being followed‐up until 6 months. We considered that given the pathology of chronic wounds 32, 33, 34, 35, 36, a relevant time horizon to assess the cost‐effectiveness of Polyheal is 12 months. Hence, patients' wound sizes in the clinical studies were interpolated and extrapolated up to 12 months using moving averages. As a result, this analysis does not consider the potential impact of the wounds that remained unhealed beyond that period. The sample size of Polyheal‐treated patients in our study is small in absolute terms, reflecting the small number of patients with chronic wounds with EB&T seen in clinical practice. Also, the results of this study are dependant on Polyheal's observed success rates being replicated in clinical practice. The inherent variability and uncertainty of using data from such a small sample of patients was addressed to some extent by the extensive sensitivity analyses. Nevertheless, the results should be viewed with some caution until more data become available which can be used to update the models. In particular, the models would benefit from data derived from a randomised controlled study comparing surgery with Polyheal, which, in addition to collecting clinical data, also prospectively collected health‐care resource use and utilities.
The primary measure of efficacy in the Polyheal studies was achieving >75% granulation. Wound size, which was a secondary efficacy measure, was used as a proxy in the economic models to determine a patient's transition from one health condition to another. However, wound area measurements or percentage changes in wound size are only superficial measurements of healing as they fail to take wound depth into account. Notwithstanding this, Polyheal is thought to trigger a synchronised series of events that provides the conditions for a stagnant wound with inefficient inflammatory process and poor proliferative phase to increase proliferation 37.
The results, however, may be confounded by certain other limitations within the models. The probabilities of outcomes and resource use have been extrapolated from a small cohort of 29 Polyheal‐treated patients with chronic wounds with EB&T. These may not be representative of all patients with chronic wounds with EB&T due to trauma in France, Germany and the UK. Moreover, due to the nature of the clinical data set and lack of a prospective comparator in two of the Polyheal studies, the models may not be predictive of the incremental differences in clinical outcomes and resource use that will be seen in clinical practice when Polyheal becomes routinely available.
Similarly, the clinical basis of the surgical arm in the models was disparate published studies 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 that were used to estimate healing rates associated with the different surgical procedures. Nevertheless, the success rates of the first‐line surgical procedures were very similar across the different studies, reporting success rates in excess of 80% 11, 12, 13, 14, 15. Similarly, the success rates associated with the second‐line surgical procedures were clustered around 70% 13, 16, 17, 18, 19, 20, 21. This is consistent with the views of the interviewed plastic surgeons who reported similar success rates in their practice.
This study was informed with assumptions about treatment patterns from six centres in each country. Hence, the levels of health‐care resource use may not be indicative of each country as a whole. The analysis estimated the cost and consequences of managing wounds up to healing or 1 year, but does not consider the potential impact of them remaining unhealed beyond that period. Moreover, the models incorporated resource use for an ‘average patient’ and do not take into account a patient's age (although the base case modelled patients with a mean age of 65 years), length of wound (although the base case modelled wounds that had remained unhealed for at least 6 months), suitability of patients for Polyheal therapy and level of clinicians' skills. The analysis was unable to consider the impact of other factors that may affect the results, such as comorbidities, underlying disease severity and pathology of the underlying disease. The models only considered direct health‐care costs borne by payers and not those incurred by patients. Also excluded are indirect costs borne by patients or society.
Despite these limitations, the models showed that initial treatment with Polyheal instead of surgery is expected to lead to a decrease in health‐care costs and a 5% improvement in the probability of healing. Hence, Polyheal potentially affords the health‐care system in each country a cost‐effective (dominant) treatment for chronic wounds with EB&T due to trauma. The unit cost of surgical procedures and hospitalisation was higher in Germany than in France and the UK. Consequently, Polyheal was found to be more cost‐effective in managing chronic wounds with EB&T due to trauma in Germany. Notwithstanding this, Polyheal might play an important role in the management of chronic wounds with EB&T due to trauma and prevent a need for surgical intervention in all three countries.
Pain is common among those with chronic wounds 38, 39, 40. Moreover, pain from chronic wounds can be intense, have a detrimental effect on physical functioning and cause psychological distress 41, 42, 43. Additionally, patients with chronic wounds may also experience severe distress as a result of a reduction of their quality of life 3. Consequently, the potential for Polyheal to be even more cost‐effective in clinical practice depends on its potential to improve patients' health status to a greater extent than surgery and conservative treatment with dressings. However, the authors could not identify any publications reporting the health‐related quality of life in patients with chronic wounds with EB&T. Consequently, the analysis excluded changes in quality of life and improvements in general well‐being of sufferers.
The analysis highlighted that defining the cost of wound care in patients with chronic wounds solely as the cost of a dressing is inaccurate. For example, the cost of a course of Polyheal treatment (€1600) was less than a quarter of the cost of surgery and no more than 21% of the total 12 monthly cost of managing a patient with a chronic wound with EB&T due to trauma. Moreover, patients treated with Polyheal have an increased chance of healing and are expected to cost less to manage than if they were treated surgically. Furthermore, use of Polyheal, as opposed to surgery, is expected to release surgical theatre time. Hence, Polyheal's acquisition cost is offset by a reduction in the requirement for surgery leading to a release of health‐care resources for use elsewhere in the system.
Conclusion
Within the models' limitations, use of Polyheal potentially affords the publicly‐funded health‐care system in France, Germany and the UK a cost‐effective treatment, compared with surgery, for the management of chronic wounds with EB&T due to trauma. However, this will be dependent on Polyheal's healing rate in clinical practice when Polyheal becomes routinely available.
Acknowledgements
This study was supported by an unrestricted educational grant from Teva Pharmaceuticals Europe BV, the Netherlands and Mediwound Ltd, Yavne, Israel, manufacturers of Polyheal. Teva Pharmaceuticals and Mediwound Ltd did not have any control of the methodology, conduct, results or conclusion of this study, or editorial involvement in this manuscript. The authors have no other conflicts of interest that are directly relevant to the content of this manuscript, which remains their sole responsibility.
The authors wish to thank the following plastic surgeons for their contributions to this study: Prof. V Casoli, CHU de Bordeaux, Centre François‐Xavier Michelet/Groupe Hospitalier Pellegrin, Bordeaux, France; Prof. F Duteille, Immeuble Jean Monnet CHU, Nantes, France; Prof. G Magalon, Brûlologie Hôpital de la Conception, Marseille, France; Prof. PY Milliez, CHU ‐ Hôpitaux de Rouen, Rouen, France; Dr A Daigeler, BG Klinik, Ludwigshafen, Germany; Prof. M Küntscher, Evangelische Elisabeth Klinik, Berlin, Germany; Dr F Lassner, Pauwelsklinik, Aachen, Germany; Dr O Lotter, Berufsgenossenschaftl Unfallklinik, Tübingen, Germany; Prof. T Schöller, Marienhospital, Stuttgart, Germany; Prof. B Stark, Universitätsklinikum, Freiburg, Germany; Mr C Caddy, Sheffield Teaching Hospital, Sheffield, UK; Mr S Hamilton, St John's Hospital, West Lothian, UK; Mr S Jeffery, Queen Elizabeth Hospital, Birmingham, UK; Mr H Lewis, Ulster Hospital, Belfast, UK; Mr P Roblin, Guys and St. Thomas's Hospitals, London, UK and Mr S Saour, St George's Hospital, London, UK. The authors also wish to thank the following dermatologists for their contributions: Dr S Blaise, Hôpital A Michallon, Grenoble, France and Prof. B Guillot, CHU de Montpellier, Hôpital Saint‐Eloi, Montpellier, France.
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