Cost/effectiveness of elivaldogene autotemcel vs. hematopoietic stem cells transplantation in patients with cerebral adrenoleukodystrophy (CALD)

Figures & data

Table 1. The model inputs.

Input parameter	Basecase value with variability (± SD*)	Probability sensitivity analysis value	References
Time delay of unfavourable events in patients with childhood-onset CALD if treated with elivaldogene autotemcel (months)	30.0 ± 8.0	Inverse normal distribution (mean 30.0, SD 8.0)	Eichler et al. [17]
Mean age in months of a child with CALD when hemisyndrome is acquired	130.0 ± 20.0	Inverse normal distribution (mean 130.0, SD 20.0)	Raymond et al. [5]
Mean age in months of a child with CALD when it experiences cognitive deterioration	118.0 ± 24.0	Inverse normal distribution (mean 118.0, SD 24.0)	Kühl et al. [19]
Mean age in months of a child with CALD when it starts falling due to cerebellar dysfunction	122.0 ± 24.0	Inverse normal distribution (mean 122.0, SD 24.0)	Pierpont et al. [20]
Mean age in months of a child with CALD when it starts having pyramidal signs	180.0 ± 20.0	Inverse normal distribution (mean 180.0, SD 20.0)	Pereira et al. [21]
Mean age in months of a child with CALD when it starts having bilateral sensitive loss	170.0 ± 20.0	Inverse normal distribution (mean 170.0, SD 20.0)	Matos et al. [22]
Mean age in months of a child with CALD when it loses vision	175.0 ± 25.0	Inverse normal distribution (mean 175.0, SD 25.0)	Kanakis and Kaltsas [23]
Mean age in months of a child with CALS it starts having hearing impairment	140.0 ± 20.0	Inverse normal distribution (mean 140.0, SD 20.0)	Eichler et al. [17]
Mean age in months of a child with CALS it starts having adrenal insufficiency	96.0 ± 18.0	Inverse normal distribution (mean 96.0, SD 18.0)	Eichler et al. [17]
Mean age in months of a child with CALD when death occurs	253.0 ± 45.0	Inverse normal distribution (mean 253.0, SD 45.0)	Eichler et al. [17]
Initial quality of life of CALD	1	Inverse beta distribution (α = 99, β = 1)	Assumption
Quality of life decrement due to hearing impairment	0.027 ± 0.002	Inverse beta distribution (α = 2.7, β = 97.3)	Tordrup et al. [24]
Quality of life decrement due to loss of vision	0.244 ± 0.034	Inverse beta distribution (α = 24.4, β = 75.6)	Lloyd et al. [25]
Quality of life decrement due to mental impairment	0.048 ± 0.012	Inverse beta distribution (α = 4.8, β = 95.2)	Fattori et al. [26]
Quality of life decrement due to motor incoordination and falls	0.042 ± 0.008	Inverse beta distribution (α = 4.2, β = 95.8)	Chittrakul et al. [27]
Quality of life decrement due to pyramidal syndrome and spasticity	0.276 ± 0.024	Inverse beta distribution (α = 27.6, β = 72.4)	Ozkan [28]
Quality of life decrement due to hemiplegia	0.120 ± 0.025	Inverse beta distribution (α = 12.0, β = 88.0)	Zhang et al. [29]
Quality of life decrement due to sensory loss	0.080 ± 0.015	Inverse beta distribution (α = 8.0, β = 92.0)	Zhang et al. [29]
Quality of life decrement due to cerebellar dysfunction	0.220 ± 0.020	Inverse beta distribution (α = 22.0, β = 78.0)	Lopez/Bastida et al. [30]
Direct costs per month per patient for treating hearing impairment in Serbia	4,422 ± 682 RSD	Inverse gamma distribution (α = 16, β = 276)	McDaid et al. [31]
Direct costs per patient for treating blind person in Serbia	15,498 ± 2,714 RSD	Inverse gamma distribution (α = 16, β = 969)	Marques et al. [32]
Direct costs per month of mental disability in Serbia	6,881 ± 1,200 RSD	Inverse gamma distribution (α = 16, β = 430)	Shahat and Greco [33]
Direct costs per month per patient for treating child with spasticity in Serbia	13,838 ± 2,439 RSD	Inverse gamma distribution (α = 16, β = 865)	de Lissovoy et al. [34]
Direct costs per month of treating hemiplegia in children	945 ± 114 RSD	Inverse gamma distribution (α = 16, β = 59)	Beecham et al. [35]
Direct costs per month of treating sensory loss	5,995 ± 1,400 RSD	Inverse gamma distribution (α = 16, β = 375)	Happich et al. [36]
Direct costs per month of treating cerebellar dysfunction	64,398 ± 7,800 RSD	Inverse gamma distribution (α = 16, β = 4,025)	Lopez/Bastida et al. [30]
Unit cost of elivaldogene autotemcel (Skysona):	324,570,900 RSD	Inverse gamma distribution (α = 16, β = 20,285,000)	Liu [37]
Gross Domestic Product per capita in Serbia 2021	RSD 917,441.90	n.a.	Statistical Office of the Republic of Serbia [38]
Referent interest rate – National Bank of Serbia in 2022	5.25%	n.a.	National Bank of Serbia [39]

*SD- standard deviation.

Figure 1. Graphic representation of the model. Rectangles in the graph represent events that may happen during the model horizon, which bear costs and influence quality of life. At each subsequent monthly cycle, it is checked within the model simulation whether each event would happen or not (depending on the time set in advance for onset of each event). The model ends when all of 480 cycles are completed.

Figure 2. Base case ICERs for all virtual patients. The x-axis: difference in QALYs gained (elivaldogene autotemcel vs HSCT); the y-axis: difference in costs (elivaldogene autotemcel vs HSCT). The line lambda 1 – the RHIF’s willingness to pay one Gross Domestic Product (GDP) per capita for one more QALY gained with elivaldogene autotemcel in comparison to the HSCT. The line lambda 2 – the RHIF’s willingness to pay three GDPs per capita for one more QALY gained with elivaldogene autotemcel in comparison to the HSCT. The line lambda 3 – the RHIF’s willingness to pay nine GDPs per capita for one more QALY gained with elivaldogene autotemcel in comparison to the HSCT.

Figure 3. Acceptability curve showing probability that elivaldogene autotemcel is considered cost/effective for treatment of CALD in comparison with HSC transplantation, which depends on willingness to pay for one additional QALY by the health insurance fund.

Figure 4. Tornado diagram showing results of one-way deterministic sensitivity analysis The bars in the graph represent variations of net monetary benefit caused by increase and subsequent decrease of model inputs listed in the right part of the graph.

Figure 5. Probability sensitivity analysis ICERs for virtual patients. The x-axis: difference in QALYs gained (elivaldogene autotemcel vs HSCT); the y-axis: difference in costs (elivaldogene autotemcel vs HSCT). The line lambda 1 – the RHIF’s willingness to pay one Gross Domestic Product (GDP) per capita for one more QALY gained with elivaldogene autotemcel in comparison to the HSCT. The line lambda 2 – the RHIF’s willingness to pay three GDPs per capita for one more QALY gained with elivaldogene autotemcel in comparison to the HSCT. The line lambda 3 – the RHIF’s willingness to pay nine GDPs per capita for one more QALY gained with elivaldogene autotemcel in comparison to the HSCT.

Table 2. Values of main output variables before and after the PSA (mean ± 99% confidence interval).

Output variables	Base case	PSA
ICER	259,848,512 ± 23,680,857 RSD	212,620,811.86 ± 250,155,384.37 RSD
Net monetary benefit	−313,439,304 ± 314,951 RSD	−315,821,281.03 ± 6,774,638.52 RSD

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Data availability statement

The data that support the findings reported in this study are available from the corresponding author upon reasonable request.