A pilot cost-effectiveness analysis of treatments in newly diagnosed high-grade gliomas: the example of 5-aminolevulinic Acid compared with white-light surgery

Abstract

Background: High-grade gliomas are aggressive, incurable tumors characterized by extensive diffuse invasion of the normal brain parenchyma. Novel therapies at best prolong survival; their costs are formidable and benefit is marginal. Economic restrictions thus require knowledge of the cost-effectiveness of treatments. Here, we show the cost-effectiveness of enhanced resections in malignant glioma surgery using a well-characterized tool for intraoperative tumor visualization, 5-aminolevulinic acid (5-ALA).

Objective: To evaluate the cost-effectiveness of 5-ALA fluorescence-guided neurosurgery compared with white-light surgery in adult patients with newly diagnosed high-grade glioma, adopting the perspective of the Portuguese National Health Service.

Methods: We used a Markov model (cohort simulation). Transition probabilities were estimated with the use of data from 1 randomized clinical trial and 1 noninterventional prospective study. Utility values and resource use were obtained from published literature and expert opinion. Unit costs were taken from official Portuguese reimbursement lists (2012 values). The health outcomes considered were quality-adjusted life-years, life-years, and progression-free life-years. Extensive 1-way and probabilistic sensitivity analyses were performed.

Results: The incremental cost-effectiveness ratios are below &OV0556;10 000 in all evaluated outcomes, being around &OV0556;9100 per quality-adjusted life-year gained, &OV0556;6700 per life-year gained, and &OV0556;8800 per progression-free life-year gained. The probability of 5-ALA fluorescence-guided surgery cost-effectiveness at a threshold of &OV0556;20000 is 96.0% for quality-adjusted life-year, 99.6% for life-year, and 98.8% for progression-free life-year.

Conclusion: 5-ALA fluorescence-guided surgery appears to be cost-effective in newly diagnosed high-grade gliomas compared with white-light surgery. This example demonstrates cost-effectiveness analyses for malignant glioma surgery to be feasible on the basis of existing data.

FIGURE 1

Influence diagram. 5-ALA, 5-aminolevulinic acid; PDeathCR, probability of death for patients with complete resection (time dependent); PDeathPR, probability of death in patients with partial resection (time dependent); Surg2CR_5ALA, probability of complete resection with 5-ALA surgery; StaCR2Pro, probability of progression in patients with complete resection; Surg2CRstand, probability of complete resection with white-light surgery; StaPR2Pro, probability of progression in patients with partial resection; Surg2D, probability of death within 4 weeks of initial debulking surgery; Surg2PR_5ALA, probability of partial resection with 5-ALA surgery; Surg2PRstand, probability of partial resection with white-light surgery.

FIGURE 2

Tornado diagrams of 1-way sensitivity analyses concerning incremental cost-effectiveness ratios, National Health Service perspective. A, incremental cost per quality-adjusted life-year gained (in euros). B, incremental cost per life-year gained (in euros). C, incremental cost per progression-free life-year gained (in euros). PDeathCR, probability of death for patients with complete resection; PDeathPR, probability of death in patients with partial resection; Progressive >W52, progressive disease state after week 52; ProgressiveW1, first week in progressive disease state; ProgressiveW2-W52, progressive disease state from week 2 to 52; StableNoTherapy, stable disease after partial or complete resection without active treatment; StableRT, stable disease after partial or complete resection receiving radiotherapy; StableTMZadj, stable disease after partial or complete resection receiving adjuvant temozolomide treatment; StableTMZcRT, stable disease after partial or complete resection receiving concomitant radiotherapy and temozolomide; StaCR2Pro, probability of progression in patients with complete resection; StaPR2Pro, probability of progression in patients with partial resection; Surg2CRGliolan, probability of complete resection with 5-aminolevulinic acid surgery.

FIGURE 3

Scatter diagram of Monte Carlo simulation results in the cost-effectiveness plane, National Health Service perspective. A, incremental cost per quality-adjusted life-year (QALY) gained. B, incremental cost per life-year (LY) gained. C, incremental cost per progression-free life-year (PFLY) gained. The gray line represents a willingness-to-pay threshold of €20000 per additional QALY, LY, or PFLY. Results are located in the upper-right quadrant, reflecting a beneficial effect of 5-aminolevulinic acid fluorescence-guided surgery in all health effects evaluated but at a higher cost. In the 3 scatterplots, the majority of the simulation results are located below the threshold line, indicating a very high probability of incremental cost-effectiveness ratio being inferior to €20000 for all health effects evaluated.

FIGURE 4

Cost-effectiveness acceptability curves, National Health Service perspective. A, incremental cost-per quality adjusted life-year gained. B, incremental cost per life-year gained. C, incremental cost per progression-free life-year gained. The acceptability curves represent, for several willingness-to-pay threshold values ranging from €0 to €50000, the probability that the incremental cost-effectiveness ratio is below the considered threshold value. 5-ALA, 5-aminolevulinic acid.