Cost-effectiveness analysis of defibrotide in the treatment of patients with severe veno-occlusive disease/sinusoidal obstructive syndrome with multiorgan dysfunction following hematopoietic cell transplantation in Spain

Figures & data

Figure 1. Model diagram. Abbreviations. VOD/SOS, veno-occlusive disease/sinusoidal obstruction syndrome; MOD, multiorgan dysfunction; CR, complete response.

Figure 2. Use of resources, unit costs, and cost per cycle for the health states of the model. Abbreviations. HCT, hematopoietic cell transplantation; VOD/SOS, veno-occlusive disease/sinusoidal obstruction syndrome; CR, complete response; BSC, best supportive care.

Table 1. Summary of the costs associated with extended hospital stay due to severe VOD/SOS.

	Defibrotide + BSC		BSC alone
Extended hospital stay, days	7.5		23.2
	ICU	Transplant unit	ICU	Transplant unit
Unit type distribution, %	30	70	60	40
Unit cost (MBDS-H),^a €	1,254.60	909.80	1,254.60	909.80
Cost per extra day of stay, €	1,013.23		1,116.68

Abbreviations. VOD/SOS, veno-occlusive disease/sinusoidal obstruction syndrome; BSC, best supportive care; ICU, intensive care unit; MBDS-H, Mínimo Básico de Datos – Hospitalización.

^aData obtained from the Ministerio de Sanidad Consumo y Bienestar Social²⁵.

Table 2. Utility values.

Health condition	Utility	Range	Reference
Utility in ‘CR state’ according to age, years			Szende et al.^27
18–24	0.951	0.945, 0.957
25–34	0.936	0.944, 0.928
35–44	0.919	0.925, 0.913
45–54	0.898	0.906, 0.890
55–64	0.874	0.884, 0.864
65–74	0.835	0.849, 0.821
≥75	0.756	0.758, 0.754
Severe VOD/SOS utility	0.208	0.166, 0.250	Aberg et al.^26

Abbreviations. CR, complete response; VOD/SOS, veno-occlusive disease/sinusoidal obstructive syndrome.

Table 3. Univariate sensitivity analysis parameters.

	Minimum value	Base case	Maximum value
Discount rate for effects, %	0	3	5
Extended stay due to severe VOD/SOS, days
Defibrotide + BSC	0	7.48	28.11
BSC alone	0	23.18	55.69
Cost per extra day of stay, €
Defibrotide + BSC	909.78	1,013.23	1,254.61
BSC alone	909.78	1,116.68	1,254.61
Average duration of treatment with defibrotide, days	14.8	17.5	20.4
Average weight, kg	47.4	53.7	60.4
Average daily dose defibrotide, mg/kg/day	23.36	25.00	26.69
Proportion in CR at day 100, %
Defibrotide arm in phase 3 study	15.3	23.5	31.8
Historical control arm in phase 3 study	0.0	9.4	19.5
Utility in ‘severe VOD/SOS’ health state	0.166	0.208	0.250

Abbreviations. VOD/SOS, veno-occlusive disease/sinusoidal obstruction syndrome; BSC, best supportive care; CR, complete response.

Table 4. Results of the base case.

	Defibrotide + BSC	BSC alone	Defibrotide + BSC vs BSC alone
Total costs, €	58,409	24,701	+33,708
Pharmacologic cost	50,352	0	+50,352
Hospital stay cost	8,057	24,701	−16,644
LYs	5.354	4.006	+1.348
QALYs	4.655	3.440	+1.214
ICER (€/LY)			25,007
ICUR (€/QALY)			27,757

Abbreviations. BSC, best supportive care; LY, life-year; QALY, quality-adjusted life-year; ICER, incremental cost-effectiveness ratio; ICUR, incremental cost-utility ratio.

Figure 3. Results of the univariate analysis: tornado diagram. Abbreviations. VOD/SOS, veno-occlusive disease/sinusoidal obstruction syndrome; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life-year.

Table 5. Results of deterministic analysis.

Parameter	Scenario	ICER vs BSC, €/LY	ICUR vs BSC, €/QALY
Base case		25,007	27,757
Temporal horizon
Pharmacologic cost	Wastage	€26,606	€2,532
KM data extrapolation	Exponential, HR from last observation	€24,701	€2,166
Long-term survival adjustment	No adjustment	€24,927	€27,669
	Goldman et al.^28	€24,947	€27,692
Utilities	Constants over time	€25,007	€26,516

Abbreviations. ICER, incremental cost-effectiveness ratio; BSC, best supportive care; LY, life-years; QALY, quality-adjusted life-year; ICUR, incremental cost-utility ratio; KM, Kaplan-Meier; HR, hazard ratio.

Figure 4. Probabilistic sensitivity analysis results. Incremental cost-effectiveness plan. Abbreviations. WTP, willingness-to-pay; QALY, quality-adjusted life-year.

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Data availability statement

Data that support the findings of this study are openly available in Ministerio de Sanidad, Consumo y Bienestar Social - Portal Estadístico del SNS - Registro de Altas de los Hospitales Generales del Sistema Nacional de Salud at https://www.mscbs.gob.es/estadEstudios/estadisticas/cmbd.htm and from the literature cited in References. Additional data that support the findings of this study are available from the corresponding author, DCR, upon reasonable request.