How the cost-effectiveness results change in the China health policy environment: an economic evaluation of glycopyrrolate/formoterol for the treatment of COPD

Figures & data

Figure 1. The structure of the Markov model for COPD.

Table 1. Classification of airflow limitation severity in COPD⁵.

GOLD classification	State	Calculation
GOLD 1	Mild	FEV1 ≥ 80% predicted
GOLD 2	Moderate	50% ≤ FEV1 < 80% predicted
GOLD 3	Severe	30% ≤ FEV1 < 50% predicted
GOLD 4	Very severe	FEV1 < 30% predicted

Abbreviations. FEV₁, forced expiratory volume in 1 s, GOLD, global initiative for chronic obstructive lung disease.

Figure 2. Structure of the Markov cycle path.

Table 2. Baseline characteristics.

Baseline characteristics	Value	Reference
Age	63.6	Lipworth et al.^9
Male	55.00%	Lipworth et al.^9
Female	45.00%	Lipworth et al.^9
Height (male, cm)	167.1	NHFPC^16
Height (female, cm)	155.8
Distribution of the disease state
Moderate	53.10%	Lipworth et al.^9
Severe	41.68%
Very severe	5.22%

Abbreviations. NHFPC, National Health and Family Planning Commission of People’s Republic of China.

Table 3. Improvement of the morning pre-dose trough FEV₁ over 24 weeks (MD (95% confidence interval), L).

Trough FEV1 improvement	GFF MDI 7.2 μg/5.0 μg	Tiotropium 18 μg	Distribution for PSA	Reference
Pooled PINNACLE analysis	0.144 (0.134–0.154)	0.117 (0.095–0.139)^b	Normal	Martinez et al.^6
NMA	0.144 (0.121–0.166)	0.121 (0.083–0.159)	Normal	Siddiqui et al.^14
Smaller NMA^a	0.144 (0.121–0.166)	0.084 (0.035–0.132)	Normal

Abbreviations. FEV₁, forced expiratory volume in 1 s; MD, mean difference; L, liter; MDI, metered dose inhaler; NMA, network meta-analysis; PSA, probabilistic sensitivity analysis.

^aSmaller NMA excluded the open label studies.

^bOpen-label arm design for tiotropium.

Table 4. Hazard ratio of all-cause mortality rate.

Disease state	HR	95% confidence interval	Distribution for PSA	Reference
Moderate	1.466	1.19–1.48	Log-normal	Ekberg-Aronsson et al.^21
Severe	3.025	1.97–2.97	Log-normal	Ekberg-Aronsson et al.^21
Very severe	5.256	2.75–5.76	Log-normal	Ekberg-Aronsson et al.^21

Abbreviations. HR, hazard ratio; PSA, probabilistic sensitivity analysis.

Table 5. Poisson regression for exacerbations.

Coefficient	IRR	95% confidence interval	Distribution for PSA
Moderate COPD	3.4273	1.2719–9.2354	Log-normal
Severe COPD	5.5455	2.0725–14.8385	Log-normal
Very severe COPD	7.2908	2.7120–19.6002	Log-normal
GFF MDI	0.9139	0.7273–1.1484	Log-normal
Tiotropium	0.8054	0.6127–1.0585	Log-normal

Abbreviations. IRR, incidence rate ratio; COPD, chronic obstructive pulmonary disease; GFF, glycopyrrolate/formoterol; MDI, metered dose inhaler; PSA, probabilistic sensitivity analysis.

Table 6. Summary of the cycle costs.

Item	Cost per cycle (CNY)	Range for OWSA	Distribution for PSA	Reference
GFF MDI (before negotiation)	1,882.79	1,317.95–2,447.63	Gamma	Menet database^26
GFF MDI (after negotiation)	584.00	408.80–759.20	Gamma	Menet database^26
Tiotropium	1,135.33	794.73–1,475.93	Gamma	Menet database^26
Maintenance cost for moderate COPD	239.27	84.20–495.89	Gamma	Experts’ opinion and published files
Maintenance cost for severe COPD	440.21	163.20–899.61	Gamma
Maintenance cost for very severe COPD	804.71	304.94–1,650.88	Gamma
Moderate exacerbation (per episode)	892.66	317.99–1,791.62	Gamma
Severe exacerbation (per episode)	4,375.76	2,425.51–6,658.47	Gamma
Life-threatening exacerbation (per episode)	47,600.77	44,370.86–52,558.74	Gamma
Pneumonia	15,497.00	NA*	Gamma	Di et al.^27

*Due to the low incidence rate, cost of pneumonia was not tested in OWSA but included in PSA.

Abbreviations. CNY, Chinese national Yuan; GFF, glycopyrrolate/formoterol; MDI, metered dose inhaler; OWSA, one-way sensitivity analysis; PSA, probabilistic sensitivity analysis.

Table 7. Utility values for different COPD states.

COPD state	Utility value (mean ± SD)	Distribution for PSA	Reference
Mild	0.786 ± 0.085	Beta	Wu et al.^30
Moderate	0.734 ± 0.158	Beta	Wu et al.^30
Severe	0.691 ± 0.155	Beta	Wu et al.^30
Very severe	0.675 ± 0.151	Beta	Wu et al.^30

Abbreviations. COPD, chronic obstructive pulmonary disease; GFF, glycopyrrolate/formoterol; MDI, metered dose inhaler; PSA, probabilistic sensitivity analysis.

Table 8. Base case analysis results.

Outcomes	GFF MDI	Tiotropium	Difference
LYG	8.1007	8.0943	0.0063
QALY	5.6051	5.6019	0.0032
Lifetime exacerbation	7.1938	7.0051	0.1887
Total costs (CNY)	27,854	33,189	‒5,335
Cost of drugs (CNY)	5,870	11,459	‒5,589
Cost of maintenance (CNY)	13,983	14,022	‒39
Cost of exacerbation (CNY)	7,903	7,656	247
Cost of AEs (CNY)	98	52	46
ICER (GFF MDI vs. tiotropium)	Dominant

Abbreviations. LYG, life-years gained; QALY, quality-adjusted life year; CNY, Chinese national YUAN; AE, adverse event; ICER, incremental cost-effectiveness ratio; GFF, glycopyrrolate/formoterol; MDI, metered dose inhaler.

Figure 3. Tornado diagram.

Figure 4. Cost-effectiveness acceptability curve.

Figure 5. Cost-effectiveness plane.

Table 9. The results of scenario analysis.

Scenario	Treatment	Cost (CNY)	QALYs	Incremental costs (CNY)	Incremental QALYs	ICER (CNY/QALY)
Original retail price	GFF MDI	40,910	5.6051	7,720	0.0032	2,442,213
	Tiotropium	33,189	5.6019
Moderate initiate state	GFF MDI	24,857	6.3044	‒5,529	0.0041	Dominant
	Tiotropium	30,386	6.3003
Severe initiate state	GFF MDI	31,157	4.8165	‒5,135	0.0027	Dominant
	Tiotropium	36,292	4.8139
Very severe initiate state	GFF MDI	35,180	4.1183	‒4,690	‒0.0066	712,918*
	Tiotropium	39,870	4.1249
Low discontinuation rate	GFF MDI	29,697	5.6222	‒7,126	0.0045	Dominant
	Tiotropium	36,823	5.6178
High discontinuation rate	GFF MDI	26,715	5.5939	‒4,222	0.0023	Dominant
	Tiotropium	30,937	5.5915
NMA	GFF MDI	27,854	5.6051	‒5,329	0.0019	Dominant
	Tiotropium	33,183	5.6032
Smaller NMA	GFF MDI	27,854	5.6051	‒5,390	0.0146	Dominant
	Tiotropium	33,244	5.5905

Abbreviations. CNY, Chinese National Yuan; QALY, quality-adjusted life year; ICER, incremental cost-effectiveness ratio; GFF, glycopyrrolate/formoterol; MDI, metered dose inhaler; NMA, network meta-analysis.

*Tiotropium compared with GFF MDI.

Figure 6. Cost-effectiveness acceptability curve for GFF MDI.

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