Cost-effectiveness analysis of budesonide/formoterol SMART therapy versus salmeterol/fluticasone plus as-needed SABA among patients ≥12 years with moderate asthma from the Chinese societal perspective

Figures & data

Table 1 Key efficacy parameter inputs (exacerbation rates and distributions of patients received different exacerbation management strategies)

Variables	Base case value	Range for OWSA	Distribution for PSA	References
Bi-weekly exacerbation rates
-Budesonide/formoterol combination therapy plus as need (100% adherence)	0.0063	(0.0051-0.0076)	Beta	[12]
-Salmeterol/fluticasone plus salbutamol (100% adherence)	0.0074	(0.0060-0.0089)	Beta	[12]
-HR of the exacerbation with 25% increase in the ICS/LABA adherence	0.89	(0.8100-0.9700)	Lognormal	[14]
Distributions of patients by different exacerbation managements strategies
Budesonide/formoterol combination therapy plus as need
-Use of OCS ≥ 3 days	66.67%	60.00%-73.33%	Dirichlet	[12]
-ED visit or hospitalization	16.67%	15.00%-18.33%
-Hospitalization with systemic steroids use	16.67%	15.00%-18.33%
Salmeterol/fluticasone plus salbutamol
-Use of OCS ≥ 3 days	42.86%	38.57%-47.14%	Dirichlet	[12]
-ED visit or hospitalization	14.29%	12.86%-15.71%
-Hospitalization with systemic steroids use	42.86%	38.57%-47.14%
OWSA, one-way sensitivity analysis; PSA, probabilistic sensitivity analysis; HR, hazard ratio; ICS, inhaled corticosteroids; LABA, long-acting β2-agonist; OCS, oral corticosteroids; ED, emergency department

Table 2 Key cost parameter inputs (direct and indirect costs)

Variables	Base case value	Range for OWSA	Distribution for PSA	References
Dosage
-Daily inhalations of maintenance ICS + LABA	2	NA	NA	Medication package insert
-Daily inhalations of as-needed budesonide/formoterol	0.305	0.245-0.365	Normal	[18]
-Daily inhalations of as-needed salbutamol	0.389	0.313-0.465	Normal
Treatment adherence rates
-Budesonide/formoterol	60%	48%-71%	Beta	Expert panel
-Salmeterol/fluticasone	60%	48%-71%	Beta
-Salbutamol (as-need therapy)	100%	NA	NA	Assumption
Drug unit costs
-Budesonide/formoterol, 160µg/4.5µg*60 (average bidding price)	220.18	179.15-265.38	Gamma	[17]
-Salmeterol/fluticasone, 50µg/250µg*60 (average bidding price)	193.60	157.52-233.34	Gamma
- Budesonide/formoterol, 160µg/4.5µg*60 (average VBP price used in scenario analysis)	183.40	NA	NA
- Salmeterol/fluticasone, 50µg/250µg*60 (average VBP price used in scenario analysis)	159.80	NA	NA
-Salbutamol (100µg*200)	22.37	18.20-26.96	Gamma
Monitoring and exacerbation costs
-Bi-weekly monitoring cost (after weighting)	33.67	See Supplemental Material Table S1
Exacerbation management costs (after weighting)
-Use of OCS ≥ 3 days	167.73	See Supplemental Material Table S1
-ED visit or hospitalization	1796.25
-Hospitalization with systemic steroids use	2493.12
Productivity loss
-Employment rate (%)	See Supplemental Material Table S2
-Daily wage per capita	82.36	67.01-99.27	Gamma	[19]
Annual work loss of patients over 21 years with no exacerbations (days)	54.40	44.26-65.57	Gamma	[20]
Annual work loss of the caregivers of 12-20 aged patients with no exacerbations (days)	11.67	9.50-14.07	Gamma	[20]
Work loss per exacerbation (days)
-Use of OCS ≥ 3 days	1.00	0.81-1.21	Gamma
-ED visit or hospitalization	6.40	5.21-7.71	Gamma	[21]
-Hospitalization with systemic steroids use	6.40	5.21-7.71	Gamma	[21]
OWSA, one-way sensitivity analysis; PSA, probabilistic sensitivity analysis; ICS, inhaled corticosteroids; LABA, long-acting β2-agonist; OCS, oral corticosteroids; ED, emergency department; VBP, volume-based procurement; NA, not applicable

Table 3 Key utility parameter inputs

Variables	Base case value	Range for OWSA	Distribution for PSA	References
Utilities
-No exacerbations	0.780	0.74-0.82	Beta	[22]
Disutility of exacerbation
-Use of OCS ≥ 3 days	0.100	0.08-0.12	Beta	[23]
-ED visit or hospitalization	0.150	0.12-0.18	Beta
-Hospitalization with systemic steroids use	0.200	0.16-0.24	Beta
OWSA, one-way sensitivity analysis; PSA, probabilistic sensitivity analysis; OCS, oral corticosteroids; ED, emergency department

Table 4 Results from Base Case Cost-effectiveness Analysis

Outcomes	Budesonide/formoterol SMART therapy	Salmeterol/fluticasone plus as-needed salbutamol	Incremental value of Budesonide/formoterol SMART therapy
Effectiveness
Exacerbation events	13.5575	15.8910	−2.3336
LY Gains	20.1067	20.1067	0.0000
QALYs Gains	15.6643	15.6566	0.0077
Costs
Total	¥98,496.18	¥98,299.80	¥196.38
Direct medical cost	¥52,774.94	¥51,991.39	¥783.55
Maintenance drug cost	¥31,986.24	¥28,088.05	¥3,898.19
Monitoring and follow-up cost	¥17,467.36	¥17,444.49	¥22.87
Reliever medication as-needed cost	¥61.78	¥2.81	¥58.97
Acute exacerbation management cost	¥3,259.56	¥6,456.04	¥-3,196.48
Adverse reaction management cost	¥890.54	¥889.37	¥1.17
Indirect cost	¥45,721.24	¥46,308.41	¥-587.17
ICER	¥25,409.98/QALY

LY, Life years; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life-year;

Figure 1 Model structure

Figure 2 OWSA Tornado Diagram. Negative values of cost per QALY gained from the tornado plot should be interpreted with caution as a negative cost per QALY gained may be caused by negative incremental costs (a good outcome) or negative incremental QALYs (a bad outcome).

Figure 3 Cost-effectiveness Plane for budesonide/formoterol vs. salmeterol/fluticasone plus salbutamol from Probabilistic Sensitivity Analysis

Figure 4 Cost-effectiveness acceptability curve