Introduction

It is estimated that 15 percent of patients with diabetes will develop foot ulcers and that 15 to 20 percent of those will progress to lower-extremity amputation.1,2 Indeed, it has been reported that foot ulcers precede 85 percent of all nontraumatic, lower-extremity amputations.3 The cost of treating diabetic foot ulcers (DFUs) is reported to range between $4,000.00 to $8,000.00 per ulcer episode and almost $28,000.00 over the first two years after diagnosis.1,3 The attributable cost of amputations is estimated at between $20,000.00 to $60,000.00.2,3 These figures motivate current efforts to develop cost-effective wound healing treatments, such as a living skin equivalent (LSE)* for DFUs.

The Apligraf Diabetic Foot Ulcer Study (ADFUS) demonstrated the efficacy of LSE as an adjunctive therapy for DFUs that are resistant to conventional therapy.4 LSE is a bioengineered living skin equivalent that consists of dermal and epidermal layers containing human keratinocytes and fibroblasts. The purpose of the current study was to evaluate the cost effectiveness of a standard dressing regimen plus LSE versus a standard dressing regimen alone for treatment of DFUs using ADFUS pivotal trial data. Because both treatment groups in the pivotal trial were treated with similar dressing regimens, the addition of LSE was cost additive. However, it was hypothesized that when the clinical benefit associated with LSE was incorporated into the cost-effectiveness equation (the incremental cost per ulcer-free month gained and the incremental cost per amputation/resection avoided), the resulting cost-effectiveness ratios would fall within an acceptable range of cost effectiveness relative to other medical interventions.

Methods

Using the ADFUS data, we computed incremental cost-effectiveness ratios of the differences in the mean costs of medical resources associated with LSE versus standard dressing care to differences in selected clinical outcomes between the treatment groups. Specifically, we examined the incremental cost per amputation/resection avoided for LSE plus standard dressing care relative to standard dressing care alone, and the incremental cost per additional ulcer-free month for LSE relative to standard dressing care. The time horizon for the cost-effectiveness analysis covered the period of the clinical trial from randomization (baseline) to six months follow up.

Costs were assigned to all nonprotocol-driven, ulcer-related clinical events, regardless of whether they differed significantly in occurrence between groups. These were identified as economically important clinical events. These included ulcer-related adverse events (AE), nonprotocol-scheduled office visits, and debridement procedures performed during office visits. We also included nonulcer-related adverse events if they differed significantly between groups. In the pivotal trial, diarrhea was the only nonulcer-related adverse event that differed in frequency between the treatment groups (p < 0.05) and, thus, was included in the cost-effectiveness analysis. The costs of these economically important events were summed to arrive at a total cost per patient. The perspective adopted was that of a commercial health plan or centralized payer. Whenever possible, national Medicare reimbursement rates were used as proxies for costs, and costs were estimated using the year 2000 US dollars.5 Because many private payers in the US look to Medicare in establishing their own cost schedules, this approach should be relevant to their concerns. We assigned costs to the AEs based on the corresponding procedures and treatment regimens recorded. With respect to the medications, costs were estimated from Drug Topics’ Redbook, published by the Medical Economics Company.