The CE Model

The study population was a hypothetical cohort of 1,000 patients with severe diabetic foot ulcers (Wagner's classification III or above) (5). Patients were assumed to be sixty years old. By assumption, there are no patients with contraindications of HBO2 therapy, such as high fever, emphysema, or pneumothorax. Furthermore, it was assumed that both control and treatment groups had similar demographic and etiological characteristics.

A decision tree model (see Figure 1) was constructed to estimate the CE ratio of incremental cost per additional quality adjusted life year (QALY) gained (9) from the adjunctive use of HBO2 therapy. The incremental cost was estimated from the total cost of HBO2 therapy minus averted costs of major and minor LEAs saved. We excluded the costs of treating side effects of HBO2 therapy because major side effects that require medical attention rarely occur (21).

Decision tree diagram for cost-effectiveness analysis of hyperbaric oxygen (HBO2) therapy at year 1 in the treatment of diabetic foot ulcers. LEA, lower extremity amputations.

Because wound care is a standard treatment for both HBO2 and non-HBO2 groups, the cost of wound care treatment was excluded from the analysis, as it will not affect the incremental costs of HBO2 treatment. All costs identified for this analysis were inflated to 2001 dollars. QALYs for each patient were derived from assigning EuroQol weights (22) to four different treatment outcomes (see Figure 1). In addition, QALYs gained from the adjunctive use of HBO2 therapy were based on the difference of total QALYs in both treatment and control groups. A discount rate of 3% (13) was applied to adjust QALYs gained in the future years. The entire analysis was performed primarily based on societal and payers' perspectives (9).

Based on the model, we estimated the CE ratio at three time intervals – 1, 5, and 12 years after HBO2 treatments. The 5-year interval was chosen to represent the private payers' perspective, because 5 years later they will automatically become Medicare beneficiaries. The 12-year interval was selected to represent the societal perspective, because the expected life expectancy for people at age 60 is approximately 20 years (1) and the life expectancy for people with diabetes is approximately 8 years shorter than that of people without diabetes (14). Two assumptions were also made for this analysis: first, the mortality rate was assumed to be constant over the 12-year period; second, foot ulcers would not reoccur once they were healed.

The probabilities of treatment outcomes for both the treatment and control groups were based on the summarized results of four prospective, controlled, clinical studies (Table 1). These studies were selected through a complete MEDLINE search between 1985 and 2001 (February). Five studies (7;17;19;20;26) were excluded from the analysis because they failed to meet one of the inclusion criteria, including prospective controlled design, diabetic etiology and the measure of treatment outcomes as primary healing and healing with minor and major LEAs. Additional model parameters used in this analysis are described in Table 2.

Scenario and Sensitivity Analyses

Scenario analyses (9) were conducted to measure the range of the CE ratios between the least (11) and most (2) efficacious outcomes of HBO2 therapy in the treatment of diabetic ulcers shown in Table 2, holding the remaining parameters constant in the model. In addition, one-way sensitivity analyses (9) were also undertaken to evaluate the impact of each parameter on the CE ratios of the base case estimation in different time periods.

CE Ratios

In the base case estimation, 155 cases of major LEAs are averted (205 LEAs in control group versus 50 LEAs in HBO2 group) and approximately 50.2, 265.3, and 608.7 QALYs are gained at years 1, 5, and 12, respectively, due to the use of HBO2 therapy in the hypothetical cohort. The base model also estimates an increase of forty-five cases of minor LEAs in the HBO2 group (130 LEAs in control group versus 175 LEAs in HBO2 group). As a result, the incremental cost of the adjunctive use of HBO2 therapy is $1,370,965, calculated from ($5,901,500 of HBO2 treatments)+($1,773,780 due to increased number of minor LEAs)−($6,304,315 due to major LEAs averted). This calculation results in an incremental cost per additional QALY gained of approximately $27,310, $5,166, and $2,255 at the 1, 5, and 12-year periods, respectively (Table 3), indicating HBO2 therapy is more cost-effective based on a long-term perspective.

Scenario and Sensitivity Analyses

In the scenario analyses, the CE ratios vary substantially across different scenarios. For example, the CE ratio at year 1 is $142,923, $27,310, and $−72,799 in the worst, base, and best case scenarios, respectively (Table 3). In addition, the broad variation of the CE ratios indicates that the results are very sensitive to the efficaciousness probabilities drawn from the existing clinical studies. Table 3 also shows the results of one-way sensitivity analyses. Based on the analyses, the CE ratios are most sensitive to the quality weights, especially for major LEA. Other parameters such as the number of HBO2 treatments per case, the HBO2 cost per treatment, and the treatment costs of major and minor LEA per case also have a significant impact on the CE ratios (see Table 3). The CE ratios are less sensitive to the mortality rate and discount rate (not shown).