The budget impact and cost-effectiveness of defibrotide for treatment of veno-occlusive disease with multi-organ dysfunction in patients post-hematopoietic stem cell transplant

Figures & data

Figure 1. Budget impact model schematic.

Table 1. Base-case model assumptions and inputs for budget impact model.

Model parameter	Assumption
Patient population	Patients with VOD with MOD approximate those of the trial^12^,^25^,^26 n = 102 defibrotide patients and n = 32 historical controls Median age of 21 years in defibrotide arm and 18 years in controls 43% pediatric patients in defibrotide arm and 44% pediatric patients in controls 45% female and 55% male in adults 40% female and 60% male in pediatric patients 88% allogeneic transplant in DF arm and 84% in historical controls
Comparators	Standard care
Daily dose	The daily dose of 6.25 mg/kg every 6 h was taken from the trial protocol Assumed 4 infusions per day Assumed adult weight of 73.9 kg and pediatric weight of 26.0 kg per phase III trial
Drug cost	Mean cost per vial (200 mg per vial) based on wholesale acquisition cost (WAC) (Analy$ource, 2016) Base case = $825 Assumed no vial sharing across days per patient
Days on therapy	21 days on therapy based on the minimum recommended treatment
Adverse events	The costs of adverse events were not included because, although both the defibrotide group and historical control patients had a high rate of overall treatment emergent adverse events (97% vs 100%, respectively), the defibrotide group and historical control demonstrated similar incidence of common adverse events. Bleeds did not significantly differ between the treatment groups (65% defibrotide and 69% controls).
Length of hospital stay	We assumed there was no difference in length of stay (LOS) based on limited trial data. However, intensity of care (and cost per day) was estimated based on mortality differences and differences in hospital costs by survival/mortality status, as described above.
Hospital costs for HSCT	Estimated cost of HSCT was higher in the pediatric population based on Premier data analysis, described below.

VOD: veno-occlusive disease; MOD: multi-organ dysfunction; HSCT: hematopoietic stem cell transplant.

Table 2. Other model inputs for budget impact model.

Model parameter	Adult estimates	Pediatric estimates	Source
Day +100 mortality reduction between defibrotide and standard care	23%	23%	Propensity score adjusted outcome of trial^12
Mean hospital cost for HSCT without VOD	$95,746	$176,122	Premier database analysis
Mean total hospitalization cost in VOD with MOD patients who are alive at day 100 post HSCT	$198,027	$295,750
Mean total hospitalization cost in VOD with MOD patients who died by day 100 post HSCT	$326,134	$486,925
Calculated cost of VOD with MOD per defibrotide patient	$264,643	$395,161	= (cost VOD with MOD hospitalization in those died) × (% died) + ((1 − % died) * (cost VOD with MOD hospitalization in those lived)
Calculated cost of VOD with MOD per standard care patient	$294,107	$439,131

VOD: veno-occlusive disease; MOD: multi-organ dysfunction; HSCT: hematopoietic stem cell transplant.

Table 3. Parameters varied in budget impact model one-way sensitivity analysis of incremental total costs.

	Adult		Pediatric
Parameter	Low value	High value	Low value	High value
Cost of 200 mg defibrotide vial	$660	$990	$660	$990
Vial sharing	Yes	No	Yes	No
Infusions per day	3.2	4.8	3.2	4.8
Dose/infusion, mg/kg	5.00	7.50	5.00	7.50
Days on therapy	16.8	25.2	16.8	25.2
Transplants/year at treatment center	80	120	80	120
Proportion deaths in control arm	60.0%	90.0%	60.0%	90.0%
Proportion deaths in defibrotide arm	41.6%	62.4%	41.6%	62.4%
% Patients with VOD with MOD	1.8%	2.8%	3.4%	5.0%
% Female patients	36%	54%	32%	48%
Body weight, Female, kg	59.12	88.68	20.80	31.20
Body weight, Male, kg	59.12	88.68	20.80	31.20
Mean hospital cost, VOD with MOD patients dead by 100 days	$260,907	$391,361	$389,540	$584,310
Mean hospital cost, VOD with MOD patients alive at 100 days	$158,422	$237,632	$236,600	$354,900
Mean hospital cost of transplant, no VOD with MOD	$76,597	$114,895	$140,898	$211,346

VOD: veno-occlusive disease; MOD: multi-organ dysfunction.

Figure 2. Cost utility analysis model schematic.

Table 4. Additional inputs for the cost utility analysis from the trial.

Model parameter	Estimate
Mean age, years
Adults	30
Pediatric	10
% adults	57%
Mean weight in kg, adults
Females	67.23
Males	79.47
Mean weight in kg, pediatrics
Females	23
Males	28
Days on therapy	23.3
Vial sharing?	No
Mortality from day 101–180 (assumed to be the same in both groups)	5.8%

Figure 3. Estimated mean long-term survival of patients who survive to 180 days (based on Phase III trial data)¹¹ undergoing HSCT and experiencing VOD with MOD.

Table 5. Range of model inputs for cost utility sensitivity analyses.

Parameter	Adult		Pediatric
	Low value	High value	Low value	High value
Days on therapy	18.6	28.0	18.6	28.0
Cost per 200 mg vial	$660	$990	$660	$990
Defibrotide dose/infusion, mg/kg	5.00	7.50	5.00	7.50
Infusions per day	3.2	4.8	3.2	4.8
Vial sharing?	Yes	No	Yes	No
Survival utility	0.69	0.95	0.69	0.95
Standard care 100-day survival	20.0%	30.0%	20.0%	30.0%
Defibrotide survival difference at 100 days	5.2%	40.8%	5.2%	40.8%
Absolute mortality days 100–180 (both arms)	4.6%	7.0%	4.6%	7.0%
Proportion of adult patients	45.6%	68.4%
% Female	30%	44%	32%	48%
Mean patient age	24	36	8	12
Mean body weight in kg, Male	63.58	95.36	22.40	33.60
Mean body weight in kg, Female	53.78	80.68	18.40	27.60
Mean hospital cost, VOD with MOD patients who died by 100 days	$260,907	$391,361	$389,540	$584,310
Mean hospital cost, VOD with MOD patients alive at 100 days	$158,422	$237,632	$236,600	$354,900

VOD: veno-occlusive disease; MOD: multi-organ dysfunction; HSCT: hematopoietic stem cell transplant.

Table 6. Results of budget impact model for 100 patients per year: adult transplant center.

	No defibrotide	With defibrotide	Difference
Total annual cost, adult treatment center, 100 HSCTs/year	$10,030,831	$10,361,537	$330,706
Hospitalization cost, no VOD with MOD	$9,354,384	$9,354,384	$0
Hospitalization cost, VOD with MOD	$676,447	$608,678	−$67,769
Defibrotide cost	$0	$398,475	$398,475
Direct hospitalization cost offset per treated patient		−$29,465
Incremental cost per treated patient		$143,785
Incremental cost per transplant patient year		$3,307

VOD: veno-occlusive disease; MOD: multi-organ dysfunction; HSCT: hematopoietic stem cell transplant.

Table 7. Results of budget impact model for 100 patients per year: pediatric transplant center.

	No defibrotide	With defibrotide	Difference
Total annual cost, pediatric treatment center, 100 HSCTs/year	$18,716,839	$18,823,224	$106,385
Total hospitalization cost, no sVOD	$16,872,488	$16,872,488	$0
Total hospitalization cost, sVOD	$1,844,351	$1,659,676	−$184,675
Defibrotide cost	$0	$291,060	$291,060
Direct hospitalization cost offset per treated patient		−$43,970
Incremental cost per treated patient		$25,330
Incremental cost per transplant patient year		$1,064

VOD: veno-occlusive disease; MOD: multi-organ dysfunction; HSCT: hematopoietic stem cell transplant.

Figure 4. Breakdown of total annual transplant center costs with or without defibrotide.

Figure 5. Budget impact model one-way sensitivity analyses for total annual incremental costs for an adult transplant center with the introduction of defibrotide for VOD with MOD. The widths of the horizontal bars represent the change in results when each parameter was varied over the ranges specified in Table 3.

Figure 6. Budget impact model one-way sensitivity analyses for total annual incremental costs for a pediatric transplant center with the introduction of defibrotide for VOD with MOD. The widths of the horizontal bars represent the change in results when each parameter was varied over the ranges specified in Table 3.

Table 8. Cost utility analysis results: incremental cost effectiveness of defibrotide versus standard care in the treatment of VOD with MOD among patients undergoing HSCT.

Treatment	Costs in US $ Base case (95% CR)	QALYs Base case (95% CR)	Lys Base case (95% CR)	ICER
Defibrotide	$463,396 ($389,220–$541,679)	4.12 (2.01–6.76)	6.87 (3.42–11.06)	$47,736 ($12,374–$178,523)
Standard care	$356,468 ($306,578–$407,083)	1.88 (0.58–3.47)	3.13 (0.98–5.73)
Difference	$106,928 (−$40,551–$176,776)	2.24 (0.77–4.29)	3.74 (1.30–7.01)

95% CR: 95% credible range; QALYs: Quality-adjusted life-years; Lys: Life years; ICER: Incremental cost-effectiveness ratio.

Figure 7. Cost utility analysis incremental cost-effectiveness ratio of defibrotide vs no defibrotide in one-way sensitivity analyses. The widths of the horizontal bars represent the change in results when each parameter was varied over the ranges specified in Table 5.

Figure 8. Cost utility analysis probabilistic sensitivity analyses of the ICER of defibrotide vs standard care among VOD with MOD patients.

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