Within-trial cost-effectiveness of novel macrophage-regulating treatment on wound healing in patients with diabetic foot ulcers

Abstract

An M1/M2 macrophage-regulating treatment, ON101 cream, has shown its superior healing efficacy for diabetic foot ulcers (DFUs) versus standard absorbent dressing, according to a phase III trial. Given its high cost, corroborating the economic value of ON101 treatment can facilitate clinical and policy decision-makings. This study sought to evaluate the cost-effectiveness of ON101 versus an absorbent dressing for patients with DFUs from Taiwan's healthcare sector perspective. This economic evaluation utilized effectiveness and cost data (in 2022 USD) from a randomized controlled trial of ON101, published literature, and Taiwan's National Health Insurance program. Incremental cost-effectiveness ratio (ICER) against willingness-to-pay (WTP) threshold was estimated to determine the cost-effectiveness of treatment. Over a mean follow-up of 12.69 weeks in the full analysis set of patients (n = 236), 6 patients would need to be treated with ON101 versus the absorbent dressing to obtain a case of complete healing, which costed US$21,128 per complete-healing case gained. This ICER value was below WTP threshold of US$32,788. Cost-effective findings were consistent across sensitivity analyses, and more remarkable for patients with Wagner grade 2 ulcers, HbA_1c >7%, and plantar ulcers. All these results were similar in modified intention-to-treat set. The high upfront drug cost of ON101 could be offset by its superior healing efficacy. Considering key prognostic factors for DFUs while optimizing the allocation of limited healthcare budgets, ON101 should be prioritized for severe cases with poor ulcer prognosis.

Fig. 1

One-way sensitivity analysis for impact of cost and effectiveness parameter variations (quantified by 95% CIs) on ICER for complete healing outcome. Abbreviations: FAS, full analyses set; mITT, modified intention to treat; HR, hazard ratio; ICER, incremental cost-effectiveness ratio; WTP, willingness-to-pay; CI, confidence interval. Notes: 1. One-way sensitivity analysis was only conducted for clinical outcome with statistically significant difference between treatment (i.e., healing outcome). 2. For complete healing outcome, there were mean follow-ups of 12.69 and 12.72 weeks under FAS and mITT settings, respectively. 3. The lower and upper bounds of 95% confidence interval from the effectiveness estimates (i.e., incidence rate and HR) were utilized to calculate the minimum and maximum values of NNT. The Wald method was applied to determine the minimum and maximum values for the cost parameters (including costs in the 16-week treatment course and costs in overall 28-week trial period). Black solid dot indicates the point estimate of ICER. The range for the black solid dot (i.e., ICER estimate) were calculated using the minimum and maximum values of NNT and of the cost parameters under different settings (i.e., FAS or mITT). 4. The baseline medical cost was not examined in one-way sensitivity analysis because it was estimated based on patient baseline characteristics using a regression model analysis (Chen et al. 2020), where between-group difference in baseline characteristics (i.e., ON101 and Absorbent dressing) was relatively small.

Fig. 2

Break-even analysis for ON101 treatment cost. Abbreviations: FAS, full analyses set; mITT, modified intention to treat; ICER, incremental cost-effectiveness ratio; WTP, willingness-to-pay. Note: ICER estimates were calculated based on the effectiveness estimated from the number needed to treat for complete healing event and the costs derived from 28 weeks of trial period.