Canadian Respiratory Journal

Review Article

Cost Effectiveness of Bosentan for Pulmonary Arterial Hypertension: A Systematic Review

Table 3

Overview of economic evaluation outcomes of included studies.


References	Comparison	Effectiveness/benefits	Costs (original currency; mean)	Costs (2017 US$; mean)	ICER (2017 US$ per QALY)	Threshold of ICER (per QALY)	Sensitivity or uncertainty analysis

Highland et al. [12]	(1) Bosentan vs. epoprostenol	Incremental effectiveness: 11 QALYs per 100 patients	Incremental costs: $3631900 per 100 patients/yr	Incremental costs: $4641721.88 per 100 patients/yr	Dominating	NA	Sensitivity analyses: results robust.
Highland et al. [12]	(2) Bosentan vs. treprostinil	Incremental effectiveness: 11 QALYs per 100 patients	Incremental costs: $4873800 per 100 patients/yr	Incremental costs: $6228922.62 per 100 patients/yr	Dominating	NA	Sensitivity analyses: results robust.

Garin et al. [13]	(1) Bosentan vs. epoprostenol	Incremental effectiveness: 5.77 QALYs per 100 patients	Incremental costs: $408213 per 100 patients/yr	Incremental costs: $452508.19 per 100 patients/yr	Dominating	NA	Sensitivity analyses had minimal impact on these results.
	(2) Bosentan vs. treprostinil	Incremental effectiveness: 5.92 QALYs per 100 patients	Incremental costs: $434684 per 100 patients/yr	Incremental costs: $481851.56 per 100 patients/yr	$81393.84	$50000
	(3) Bosentan vs. iloprost	Incremental effectiveness: 3.09 QALYs per 100 patients	Incremental costs: $3466486 per 100 patients/yr	Incremental costs: $3842634.40 per 100 patients/yr	Dominating	NA
	(4) Bosentan vs. Sitaxentan	Incremental effectiveness: 0.16 QALYs per 100 patients	Incremental costs: $474 per 100 patients/yr	Incremental costs: $525.43 per 100 patients/yr	$3283.94	$50000
	(5) Bosentan vs. ambrisentan	Incremental effectiveness: 0 QALYs per 100 patients	Incremental costs: $0 per 100 patients/yr	Incremental costs: $0 per 100 patients/yr	$0	NA
	(6) Bosentan vs. sildenafil	Incremental effectiveness: 0 QALYs per 100 patients	Incremental costs: $3153535 per 100 patients/yr	Incremental costs: $3495725.08 per 100 patients/yr	Dominated	NA

Coyle et al. [14]	(1) Bosentan vs. ambrisentan 5mg	Patients with FC II Incremental effectiveness: −0.73 QALYs per person (treatment, 3.904 QALYs; comparator, 4.634 QALYs)	Patients with FC II Incremental costs: Can$29095 per person (treatment, Can$406282; comparator, Can$377187)	Patients with FC II Incremental costs: $24105.22 per person (treatment, $336604.81; comparator, $312499.59)	Dominated	NA	Extensive sensitivity analyses: results robust. Probabilistic sensitivity analysis: results robust.
	(1) Bosentan vs. ambrisentan 5mg	Patients with FC III Incremental effectiveness: −0.22 QALYs per person (treatment, 2.960 QALYs; comparator, 3.180 QALYs)	Patients with FC III Incremental costs: Can$61406 per person (treatment, Can$412979; comparator, Can$351573)	Patients with FC III Incremental costs: $50874.90 per person (treatment, $342153.27; comparator, $291278.38)	Dominated	NA
	(2) Bosentan vs. ambrisentan 10mg	Patients with FC II Incremental effectiveness: −0.313 QALYs per person (treatment, 3.904 QALYs; comparator, 4.217 QALYs)	Patients with FC II incremental costs: Can$28759 per person (treatment, Can$406282 comparator, Can$377523)	Patients with FC III Incremental costs: $23826.84 per person (treatment, $336604.81; comparator, $312777.96)	Dominated	NA
	(2) Bosentan vs. ambrisentan 10mg	Patients with FC III Incremental effectiveness: −0.083 QALYs per person (treatment, 2.960 QALYs; comparator, 3.043 QALYs)	Patients with FC III Incremental costs: Can$36095 per person (treatment, Can$412979; comparator, Can$376884)	Patients with FC III Incremental costs: $29904.7 per person (treatment, $342153.27; comparator, $312248.55)	Dominated	NA
	(3) Bosentan vs. sildenafil	Patients with FC II incremental effectiveness: −0.7593 QALYs per person (treatment, 3.904 QALYs; comparator, 4.663 QALYs)	Patients with FC II incremental costs: Can$260028 per person (treatment, Can$406282 comparator, Can$146254)	Patients with FC II incremental costs: $215433.31 per person (treatment, $336604.81; comparator, $121171.50)	Dominated	NA
	(3) Bosentan vs. sildenafil	Patients with FC III Incremental effectiveness: −0.324 QALYs per person (treatment, 2.960 QALYs; comparator, 3.284 QALYs)	Patients with FC III Incremental costs: Can$231860 per person (treatment, Can$412979; comparator, Can$181119)	Patients with FC III Incremental costs: $192096.11 per person (treatment, $342153.27; comparator, $150057.17)	Dominated	NA
	(4) Bosentan vs. tadalafil	Patients with FC II Incremental effectiveness: −0.098 QALYs per person (treatment, 3.904 QALYs; comparator, 4.002 QALYs)	Patients with FC II Incremental costs: Can$253037 per person (treatment, Can$406282 comparator, Can$153245)	Patients with FC II Incremental costs: $209641.26 per person (treatment, $336604.81; comparator, $126963.55)	Dominated	NA
	(4) Bosentan vs. tadalafil	Patients with FC III Incremental effectiveness: −0.053 QALYs per person (treatment, 2.960 QALYs; comparator, 3.013 QALYs)	Patients with FC III Incremental costs: Can$212395 per person (treatment, Can$412979; comparator, Can$200584)	Patients with FC III Incremental costs: $175969.35 per person (treatment, $342153.27; comparator, $166183.93)	Dominated	NA
	(5) Bosentan vs. supportive care	Patients with FC II Incremental effectiveness: 0.686 QALYs per person (treatment, 3.904 QALYs; comparator, 3.128 QALYs)	Patients with FCII Incremental costs: Can$251126 per person (treatment, Can$406282 comparator, Can$155156)	Patients with FCII Incremental costs: $208058.00 per person (treatment, $336604.81; comparator, $128815.82)	$303291.55	$165700.08 (Can$200000)
	(5) Bosentan vs. supportive care	Patients with FC III Incremental effectiveness: 0.273 QALYs per person (treatment, 2.960 QALYs; comparator, 2.687 QALYs)	Patients with FC III Incremental costs: Can$208694 per person (treatment, Can$412979; comparator, Can$204285)	Patients with FC III Incremental costs: $172903.07 per person (treatment, $342153.27; comparator, $169250.2)	$633344.58	$165700.08 (Can$200000)

Dranitsaris et al. [15]	(1) Bosentan vs. ambrisentan	NA	Incremental costs: Can$16302 per patient (treatment, Can$164745; comparator, Can$148443)	Incremental costs: $14956.40 per patient (treatment, $151146.60; comparator, $136190.20)	NA	NA	One-way sensitivity analysis: results sensitive to sildenafil dose, ambrisentan daily drug cost, and bosentan daily drug cost.
	(2) Bosentan vs. sitaxentan	NA	Incremental costs: Can$6307 per patient (treatment, Can$164745; comparator, Can$158444)	Incremental costs: $5786.41 per patient (treatment, $151146.60; comparator, $145365.70)	NA	NA
	(3) Bosentan vs. sildenafil	NA	Incremental costs: Can$116394 per patient (treatment, Can$164745; comparator, Can$48351)	Incremental costs: $106786.59 per patient (treatment, $151146.60; comparator, $44360.01)	NA	NA
Wlodarczyk et al. [16]	Bosentan vs. conventional care	At 5years incremental effectiveness: 1.39 life expectancy	At 5years incremental costs: A$116929 for each patient	At 5years incremental costs: $101787.70 for each patient	$73228.56	$41928.72 (A$60000)	One-way sensitivity analysis: removing the PBS continuation rules from the model, halving of the annual mortality rate in patients treated with conventional therapy, and changing mortality and hospitalization RR affected the results.
		At 10years incremental effectiveness: 2.93 life expectancy	At 10years incremental costs: A$181808 for each patient	At 10years incremental costs: $158265.43 for each patient	$54015.51	$41928.72 (A$60000)
		At 15years incremental effectiveness: 3.87 life expectancy	At 15years incremental costs: A$216331 for each patient	At 15years incremental costs: $188318.00 for each patient	$48660.98	$41928.72 (A$60000)

Stevenson et al. [17]	Bosentan vs. palliative therapy	Patients with iPAH Incremental effectiveness: 0.37 QALYs per patient (treatment, 3.32 QALYs; comparator, 2.95 QALYs)	Patients with iPAH Incremental costs: £69000 per patient (treatment, £134000; comparator, £203000)	Patients with iPAH Incremental costs: $111639.98 per patient (treatment, $216808.07; comparator, $328448.05)	Dominating	NA	The results were similar in both the deterministic and probabilistic analyses.
Stevenson et al. [17]	Bosentan vs. palliative therapy	Patients with PAH-CTD Incremental effectiveness: 0.15 QALYs per patient (treatment, 1.36 QALYs; comparator, 1.21 QALYs)	Patients with PAH-CTD Incremental costs: £32000 per patient (treatment, £62000; comparator, £94000)	Patients with PAH-CTD Incremental costs: $51775.06 per patient (treatment, $100314.18; comparator, $152089.25)	Dominating	NA

Fan et al. [18]	Bosentan vs. palliative therapy	Incremental effectiveness: 6.19 QALYs per person (treatment, 7.23 QALYs; comparator, 1.04 QALYs)	Incremental costs: ¥439046.77 per patient (treatment, ¥504293.75; comparator, ¥65246.98)	Incremental costs: $125227.26 per patient (treatment, $143837.35; comparator, $18610.09)	$20230.58	$39815.46 (¥139593)	Sensitivity analyses: results robust.

Barbieri et al. [19]	Bosentan vs. ambrisentan	NA	Incremental costs: €1112145 (treatment, €87594291; comparator, €86482146)	Incremental costs: $1184990.49 (treatment, $93331717.06; comparator, $92146726.56)	NA	NA	The sensitivity analysis corroborated the base case findings.

Note. “Dominating” denotes bosentan treatment producing more QALYs at a lower cost, whereas “dominated” denotes bosentan producing less QALYs at a higher cost. ICER: incremental cost-effectiveness ratio; QALY: quality-adjusted life-year; yr: year; PAH: pulmonary arterial hypertension; FC: functional class; NA: not applicable; CTD: connective tissue disease.