Cost vs Healing Rates of Two Advanced Wound Therapies: A Pilot Study

Objective. The aim of this study was to compare healing rates while considering costs between 2 skin substitute products.   Materials and Methods. A retrospective pilot study was completed in 2012. The healing rates and costs of 2 products (Apligraf, Organogenesis, Canton, MA [product A] and Matristem, ACell, Inc, Columbia, MD [product B]) as advanced treatment modality for patients with venous ulcers and diabetic foot ulcers at the institution were compared by a retrospective chart review of 9 patients. Results. Four patients used product A, 3 patients with venous ulcers and 1 with a diabetic foot ulcer. Two patients healed with 1 application of the product. Five patients used product B, 3 with venous ulcers and 2 with diabetic foot ulcers, as an advanced treatment modality to aid in wound healing. Although none of these patients healed, week-to-week data showed a significant reduction in wound size and volume in these patients. Conclusion. Product A is the skin substitute that produced the best healing results. In addition, this study identified that there is not an established protocol for the application of product B and patient compliance and lack of knowledge about the application are key factors why the patients using product B did not heal.

  Wound healing is a complex process in which the body either regenerates or forms a scar. Regeneration is the preferred method of wound healing because it replaces the lost tissue with more of the same type of tissue, as well as maintains normal function and appearance.¹ Scar formation occurs when lost tissue is replaced by new connective tissue proteins because the involved tissue is incapable of regeneration.¹ Wounds that fail to proceed through the normal repair process to closure become chronic wounds, such as vascular ulcers and diabetic foot ulcers, that are considered difficult and expensive to heal.¹

  Venous ulcers develop as a result of impaired return of venous blood from the tissues to the heart, or chronic venous insufficiency.² Venous ulcers affect more than 7 million Americans, who also represent 70%-90% of the lower extremity wounds being treated in the US health care system.³ These shallow wounds can produce moderate to large amounts of drainage, which frequently cause periwound maceration. These types of wounds can also have thin layers of yellow slough, a form of necrotic tissue that, if left in the wound, can attract bacteria which leads to infection.³ Wounds with necrotic tissue need to be debrided,3 which facilitates healing by shifting the wound from a chronic state to an active phase of healing. The standard of care for treating venous ulcers is compression therapy, especially multilayer compression, which decreases edema and also controls drainage. However, some patients cannot tolerate multilayer compression therapy, and other forms of sustained graduated compression for the management of venous leg ulcers can be used. This promotes venous return and decreases edema in the limb tissues.³

  Diabetic foot ulcers are another form of a chronic wound related to diabetes. Patients with diabetes often lose sensation in their feet and develop structural deformities and callouses due to increased pressure.⁴ Diabetic wounds can have moderate amounts of drainage, and a wound bed that can be pink, pale, or necrotic. If the wound bed is necrotic, debridement is required to prevent infection and stimulate the healing process.³ Diabetic wounds are staged from 0 to 5 on the Wagner Scale. Stage 0 indicates pre-ulcer status with no open lesions and stage 5 indicates extensive gangrene and necrosis beyond salvage; because the viability of tissue at this stage is questionable, amputation is considered.⁴ Diabetic foot ulcers can easily become infected and treatment is often challenging.

  The standard of care for treating diabetic foot ulcers is the total contact cast, an offloading cast where the total plantar surface of the foot is casted to distribute weight onto the upper leg to provide pressure relief.⁴ The total contact cast is contraindicated in patients with an untreated infection or osteomyelitis, a very deep wound, or a large amount of edema in the foot.⁴ For patients who cannot use a total contact cast, the goal would be nonweight bearing status and dressing selection to maintain a moist wound bed, contain exudate, and treat infection until the appropriate time for application of the total contact cast.³

  Chronic wounds provide a clinical and economic challenge to health care providers and patients.⁵ Patients with chronic wounds often need advanced treatment modalities in conjunction with the standard of care to accelerate the healing process. In recent years, skin substitutes (ie, bioengineered tissue containing either dermal or epidermal cells, or both) have been created. Apligraf, Organogenesis, Canton, MA (product A), one example of a skin substitute, has a dermal layer that is composed of bovine type 1 collagen seeded with cultured human fibroblasts. It has an epidermal layer composed of cultured human keratinocytes that are induced to stratify the architecture of the human epidermis.⁵ This product, which requires temperature control, is usually sent overnight by the manufacturer and delivered fresh and ready to use. Research by Felder et al⁵ indicated that 5 applications was the average needed to heal patients with chronic wounds, such as venous and diabetic foot ulcers, in 8 to 12 weeks. The average cost is $1,700 per application.

  Matristem, ACell, Inc, Columbia, MD (product B), a noncross-linked acellular dermal regeneration matrix derived from porcine urinary bladder, is another type of skin substitute.⁶ This product has a basement membrane, which is conducive to epithelial and endothelial cell attachment, proliferation, and differentiation.⁷ In addition, its surface supports the growth of new blood vessels and facilitates the proliferation of connective tissue, which allows for healing promotion.⁷ Product B comes in a sheet or powder and has a 2 year shelf-life when stored at room temperature.⁶ LeCheminant and Field⁶ found that an average of 9 applications were required for wound closure in 9-18 weeks. The average cost of product B is $70-$100 per application, depending whether a sheet or the powder is used.

  When used in conjunction with standard of care, skin substitutes act as scaffolds to enhance the tissue healing process. Nurse case managers at the authors’ institution (Morristown Wound Healing Center, Morristown, NJ), recommend the use of skin substitutes in combination with the standard of care when a patient’s wound fails to meet institutional benchmarks. The institutional benchmarks for outcomes are 20% healed at 4 weeks, 40% healed at 8 weeks, 60% healed at 12 weeks, and 100% healed by week 16. When these types of products are applied, patients are instructed to leave the dressing intact under the outer dressing for 1 week, until their next follow-up visit.

  To assess progress, patients with venous ulcers have weekly appointments to have their compression wraps changed, while patients with diabetic foot ulcers have weekly appointments to have their total contact casts changed. At each visit, the wounds are measured and tracked. Photographs are taken at 4-week intervals or when significant improvement or deterioration is noted. At this institution, physicians consider using a skin substitute when the patients’ wounds fail to heal by 20% at the 4 end of weeks, 60% at the end of 8 weeks, or 90% at the end of 12 weeks. Physicians and nurse case managers evaluate all the factors that might prevent wound healing, such as nutrition, infection, and compliance with standards of care and, if there is no issue, a skin substitute is applied. Skin substitute products, in general, are costly no matter what type is utilized. The amount of research comparing the cost of these 2 skin substitutes vs their healing rates is limited. A retrospective chart review was conducted to compare healing rates while considering costs between the 2 skin substitute products. In these hard economic times, cost-containment may be equally important to the patient as wound healing.

  A retrospective pilot study was completed in 2013. The healing rates and costs of products A and B as advanced treatment modalities for patients with venous ulcers and diabetic foot ulcers at the institution were compared by a retrospective chart review of 9 patients. Institutional Review Board approval was obtained. Retrospective chart reviews from January 1, 2012 to December 31, 2012 were conducted using the electronic medical record. Patients were de-identified to protect their personal information, and then classified by age and gender. Patients were further categorized by their comorbidities and whether they had a venous ulcer or diabetic foot ulcer. The number of applications of each product that produced a healed wound was then evaluated. Patients who had either product A or product B applied to either a venous ulcer or a diabetic foot ulcer as an advance treatment modality were evaluated and included in the current study. Patients with other types of lower extremity wounds, patients who had both products A and B applied to their wounds, or who had another form of skin substitute applied to their wounds, were excluded.

  Data were collected and entered into an Excel 2010 spreadsheet including age, gender, product applied, patient’s comorbidities, wound type, wound measurements, and wound volume. A generalized skin substitute report through the electronic medical record revealed that 14 patients were identified as having skin substitutes applied to their venous ulcers or diabetic foot ulcers. Five patients who had either product A or B applied to their diabetic foot ulcer or venous ulcer were excluded because another form of skin substitute had also been applied to their wounds. Therefore, 9 patient records were included in the review.

  Four patients were identified as using product A as an advanced treatment modality to aide in wound healing. All 4 patients were male. The age range of the patients was 25-80 years of age. Two (50%) patients had hypertension, peripheral vascular disease, and diabetes; 3 (75%) patients had product A applied to venous ulcers; and 1 (25%) patient had product A applied to a diabetic foot ulcer. After 1 application, the patient with the diabetic foot ulcer experienced a 20% decrease in wound size and volume in 2 weeks. The patient’s wound healed in 10 weeks. Product A had 6 total applications with a 50% healing rate between 4 patients.

  One of the 3 (33%) patients who had product A applied to a venous ulcer healed. This patient, who was 25 years of age, had a 95% reduction, exceeding benchmark, in wound size and volume in 2 weeks after the first application; the patient healed in 8 weeks. The other 2 patients whose venous ulcers were treated with product A did not heal. An 80-year-old patient who did not heal experienced a 65% reduction in wound size and volume with 1 application of product A, but the patient ultimately stopped coming to the institution due to financial reasons and was lost to followup. The other patient who did not heal was 73 years of age and received 3 applications of product A. The first application was at week 5, with an 18% reduction in wound size and volume recorded at the week 6 visit. The second application was at week 8, with a 55% reduction in wound size and volume at the week 9 visit. The last application was applied at the week 12 visit, with a 17% reduction in size and volume at week 13. This patient was admitted to the hospital for other medical reasons and did not come back to the institution for additional follow-up visits.

  Five patients were identified as using product B as an advanced treatment modality to aid in wound healing. Three (60%) patients were females and 2 (40%) patients were male. The age range of the patients was 51-80 years of age. Three (60%) of the patients had venous ulcers and 2 (40%) patients had diabetic foot ulcers. In the venous ulcer group, the incidence of hypertension was 80%, peripheral vascular disease was 80%, and a history of diabetes was 60%. In the diabetic foot ulcer group, 100% of the patients had hypertension, as well as diabetes. No patients in this group experienced complete wound healing, but there was a significant decrease in wound size and volume noted between applications that was unlikely to have been achieved with the standard of care alone.

  One patient, 70 years of age, with a diabetic foot ulcer had product B applied in week 10 of treatment, but did not have a return visit until week 14, when a 52% reduction is wound size and volume was noted. This patient was having other medical issues and was eventually placed in a skilled nursing facility and lost to followup. The other patient with a diabetic foot ulcer (age 51) had product B applied at week 6 and had an increase in wound size by 14%. This patient was noted to have an issue with compliance of off-loading. Product B was reapplied at week 7, and a 31% reduction in wound size and volume was noted at the week 8 visit; however, the patient developed an infection that led to an amputation.

  One of the 3 patients with a venous ulcer, who was 63 years old, had product B applied at week 23 and was noted to have 40% reduction in wound size and volume at the week 25 visit. The authors believe this outcome would have been highly unlikely with the standard of care alone. This patient was eventually admitted to the hospital for other medical reasons and was lost to followup.

  The second patient, 62 years of age and with a venous ulcer, had product B applied at week 10, and was noted to have a 33% reduction in wound size and volume at the week 11 visit. There was an additional 14% reduction in wound size and volume at the week 12 visit, during which the patient received a second application of product B. There was a 12% increase in wound size and volume noted at the week 13 visit, during which the patient was noted to have compliance issues with care. At that time, the physician chose to administer a third application of product B, and there was another 35% reduction in wound size and volume noted by week 15. This patient did not return and was lost to followup in week 17 of treatment.

  The third patient, 80 years old, with a venous ulcer was treated with product B at week 9 and noted to have a 25% reduction in wound size at the week 10 visit. This particular patient only had 1 application of product B due to insurance issues, and was followed for 6 more weeks at the institution.

  While product A results were the most effective, the cost of the product may be prohibitive to patients. In addition, it is a special order product, must be ordered in advance, arrives in a Petri dish, and must be stored in a temperature-controlled container. It may be fenestrated prior to application, which is not required, but may make it more difficult to use, as the fenestration gives it a flimsy consistency.

  When looking at week-to-week data, product B showed significant reductions in wound size and volume. At $75-$100 an application, health care providers may find this skin substitute more accessible, as it may be kept in stock at room temperature and does not have to be special ordered. Physicians may choose between a powder or a sheet and, in the authors’ experience, the product is easier to apply than product A. However, because of the ease of application, some patients might not consider it a special procedure best performed by the physician, thus reducing patient compliance to follow-up protocol. Many patients remove the product at home, not adhering to instructions to leave it in place until their next clinic visit.

  Among the limitations of this retrospective study was the lack of a specific protocol for application from the product B manufacturer at the time the study was performed. That, combined with a possible lack of patient compliance, may have been why wounds did not heal. In addition, these findings cannot be generalized due to the small sample size and the lack of standardized treatment protocol for both products.

  Findings from this study indicate that product A is the skin substitute that produced the best healing results in this small sample. This study also identified that, at the time of the study, there was not an established protocol for the application of product B. At the time of publication, a protocol for the application of product B had not been developed by the manufacturer. Patient compliance, as well as lack of knowledge about application, could also be key factors as to why wounds treated with product B did not heal. The authors suggest that product B might be better utilized as a wound bed preparation agent to help promote a good granulating wound base, and product A may then be used as the next level of therapy.

  The biggest limitation to this retrospective study is the small sample size. A prospective study evaluating all of the skin substitutes used at the author’s institution on all types of wounds, as well as developing an institution-specific protocol for all skin substitutes, might be beneficial to help determine which skin substitute works best on certain types of wounds. Additional research is needed. This small study does provide implications for nurses and other clinicians caring for wounds including compliance with treatment protocols, standardized regimen of all skin substitutes, cost concerns for patient whose insurances might not cover the products and applications, and patient education regarding how and why skin substitutes are used to aide in wound healing.

  The author are from the Morristown Wound Healing Center, Morristown, NJ.

Address correspondence to:
Carla Meixsell-Arnold, BSN, RN, CWOCN
435 South Street
Suite 320
Morristown, NJ 07960
Carla.Meixsell-Arnold@atlantichealth.org

Disclosure: The author discloses no financial or other conflicts of interest.