Economic Evaluation of Umeclidinium/Vilanterol versus Umeclidinium or Salmeterol in Symptomatic Non-Exacerbating Patients with COPD from a UK Perspective Using the GALAXY Model

Figures & data

Figure 1 Infographic summary of the study background and base case results.

Table 1 Model Inputs

Parameter	Overall Input Value for Subgroup with No Exacerbations in Prior 12 Months (N = 2032)			Source
Demographics and baseline characteristics (pooled across treatment arms)
Female, %	40			EMAX trial data^a
Age, years, mean (SD)	64.6 (8.4)			EMAX trial data^a
BMI, %
Low (<21)	9.7			EMAX trial data^a
Medium (21–30)	58.0			EMAX trial data^a
High (>30)	32.3			EMAX trial data^a
Any CV comorbidity, %	45			EMAX trial data^a
Any other comorbidity, %	55			EMAX trial data^a
mMRC score ≥2, %	40			EMAX trial data (assumed same as CAT score ≥21)^Citation22
Current smoker, %	51			EMAX trial data^a
Height, cm, mean (SD)	169.5 (9.5)			EMAX trial data^a
Fibrinogen, μg/dL, mean (SD)	453.4 (104.7)			Predicted from risk equation^Citation11
Exacerbations in prior year, mean	0			Subgroup definition
Baseline SGRQ score, mean (SD)	44.72 (16.16)			EMAX trial data^a
Baseline FEV1% predicted, mean (SD)	55.7 (12.8)			EMAX trial data^a
6MWD, m, mean (SD)	385.3 (121.4)			Predicted from risk equation^Citation11
Treatment Effects	UMEC/VI (n = 689)	UMEC (n = 680)	SAL (n = 663)
Trough FEV1 at Week 24, mL (95% CI)
LS mean CFB	128 (111, 145)	58 (40, 76)	−9 (−27, 9)	EMAX trial data
UMEC/VI vs comparator mean difference	–	70 (45, 95) P<0.001	137 (112, 162) P<0.001	EMAX trial data
SGRQ score^b at Week 24 (95% CI)
LS mean CFB	−5.12 (−6.08, −4.16)	−5.02 (−6.02, −4.02)	−3.68 (−4.69, −2.68)	EMAX trial data^a
UMEC/VI vs comparator mean difference	–	−0.10 (−1.49, 1.29) P=0.888	−1.44 (−2.83, −0.05) P=0.043	EMAX trial data^a
Moderate and severe exacerbation reduction rate
UMEC/VI vs comparator relative risk		1.0	1.0	Assumption
Drug Costs per Day, 2020 £	UMEC/VI	UMEC	SAL
Base case	1.08	0.92	0.81^c	Supplementary Table S3
Scenario: SAL price (branded formulations for an effective dose of 50 µg)	1.08	0.92	1.02^d	Supplementary Table S3
Scenario: SAL price (50 µg formulation)	1.08	0.92	1.17^e	Supplementary Table S3
Healthcare Costs per Year or per Exacerbation, 2020 £	Overall Input Value
COPD severity (FEV1% predicted)
Moderate to severe (50–80%)	267			Supplementary Table S6
Severe (30–<50%)	831			Supplementary Table S6
Very severe (<30%)	2376			Supplementary Table S6
Exacerbation
Moderate	644			Supplementary Table S6
Severe	6929			Supplementary Table S6
Rescue Medication Costs	UMEC/VI	UMEC	SAL
Salbutamol inhalations/day, mean	1.56	1.84	1.77	EMAX trial data^a
	Overall Input Value
Salbutamol cost per inhalation, 2020 £	0.06			BNF 2020^Citation34
Treatment Discontinuation, % (Scenario Analyses)	UMEC/VI	UMEC	SAL
Base case, probability of discontinuation in all years	0	0	0	Assumption
Scenario: Discontinuation in first year only, no discontinuation in subsequent years
Probability of discontinuation in first year	13	19	16	Assumption (based on EMAX trial data at Week 24)
Probability of discontinuation in subsequent years	0	0	0	Assumption
Scenario: Equal rate of discontinuation in first and subsequent years
Probability of discontinuation in first year	13	19	16	Assumption (based on EMAX trial data at Week 24)
Probability of discontinuation in subsequent years	13	19	16	Assumption (equal to first year)
Subsequent Treatment Costs per day, 2020 £ (Scenario Analyses)
Weighted average cost	1.28	1.05	1.03	Supplementary Table S5
Patient Productivity Costs (Scenario Analyses)
Mean duration of exacerbation, days (SE)
Moderate	12.2 (0.12)			IMPACT trial data^a
Severe	13.4 (0.30)			IMPACT trial data^a
Average UK earnings per day, 2020 £	106.06			ONS, May 2020^Citation35

Notes: ^aData not previously published. ^bConverted to SGRQ-C score using a revised version of the SGRQ questionnaire and scoring system as previously described.^20,36 cBase case analysis (weighted average cost across branded and generic formulations) for an effective dose of 50 μg. ^dScenario analysis of weighted average of only branded products for an effective dose of 50 μg. ^eScenario analysis of 50 μg formulation only.

Abbreviations: 6MWD, 6-minute walk distance; BMI, body-mass index; BNF, British National Formulary; CAT, COPD Assessment Test; CFB, change from baseline; CI, confidence interval; COPD, chronic obstructive pulmonary disease; CV, cardiovascular; FEV₁, forced expiratory volume in 1 second; LS, least squares; mMRC, modified Medical Research Council dyspnea scale; ONS, Office for National Statistics; SAL, salmeterol; SD, standard deviation; SE, standard error; SGRQ, St George’s Respiratory Questionnaire; UMEC, umeclidinium; VI, vilanterol.

Table 2 Cumulative and Incremental Predicted Outcomes for UMEC/VI versus UMEC and SAL Over a 10-Year Horizon

	UMEC/VI	UMEC	UMEC/VI vs UMEC Incremental Difference	UMEC/VI	SAL	UMEC/VI vs SAL Incremental Difference
Cumulative exacerbations
Moderate	3.691	3.762	−0.071	3.622	3.762	−0.140
Severe	0.889	0.954	−0.064	0.831	0.954	−0.122
PPPY	0.109	0.119	−0.009	0.101	0.119	−0.017
Total	4.580	4.716	−0.136	4.453	4.716	−0.263
PPPY	0.563	0.586	−0.023	0.542	0.586	−0.044
Health outcomes
Survival at end of time horizon, %	55.3	53.4	1.9	57.1	53.4	3.8
Accumulated LYs (undiscounted)	8.136	8.046	0.090	8.219	8.046	0.174
Accumulated QALYs	4.844	4.789	0.055	4.993	4.789	0.204
Costs
Accumulated total costs, £	13,160	13,850	−690	12,240	13,575	−1336
Drug costs	3086	2670	416	3114	2396	719
Non-drug costs	10,074	11,180	−1106	9125	11,180	−2054
Incremental results, mean (95% range)
Costs, £			−690 (−1306, −231)			−1336 (−2032, −1006)
LYs			0.090 (0.035, 0.158)			0.174 (0.076, 0.286)
QALYs			0.055 (−0.059, 0.168)			0.204 (0.079, 0.326)
ICER/QALY			Dominant			Dominant

Abbreviations: ICER, incremental cost-effectiveness ratio; LY, life-year; PPPY, per-patient per-year; QALY, quality-adjusted life-year; SAL, salmeterol; UMEC, umeclidinium; VI, vilanterol.

Table 3 Scenario and Sensitivity Analyses

Scenario Analyses			UMEC/VI vs UMEC				UMEC/VI vs SAL
			LYs	QALYs	Costs	ICER/QALY	LYs	QALYs	Costs	ICER/QALY
5-year time horizon			0.019	0.015	£0	£4	0.035	0.086	−£44	Dominant
Lifetime horizon			0.321	0.133	−£504	Dominant	0.641	0.394	−£947	Dominant
0% discount rate			0.090	0.068	−£831	Dominant	0.174	0.243	−£1654	Dominant
5% discount rate			0.090	0.050	−£639	Dominant	0.174	0.190	−£1222	Dominant
Discontinuation in first year only			0.090	0.055	−£684	Dominant	0.174	0.204	−£1359	Dominant
Discontinuation in first and subsequent years			0.090	0.055	−£663	Dominant	0.174	0.204	−£1403	Dominant
Patient productivity costs included			0.090	0.055	−£853	Dominant	0.174	0.204	−£1651	Dominant
SAL price (weighted average of branded formulations)			-	-	-	-	0.174	0.204	−£1857	Dominant
SAL price (50 µg formulation only)			-	-	-	-	0.174	0.204	−£2252	Dominant
ITT data			0.087	0.026	−£787	Dominant	0.182	0.228	−£1866	Dominant
Alternate health state and exacerbation event costs			0.090	0.055	-£539	Dominant	0.174	0.204	−£1035	Dominant
Sensitivity Analyses	Base Case Value	Analysis Value	LYs	QALYs	Costs	ICER/QALY	LYs	QALYs	Costs	ICER/QALY
Fibrinogen lower CI (ECLIPSE data)	453.4	448.7	0.090	0.055	−£692	Dominant	0.172	0.203	−£1339	Dominant
Fibrinogen upper CI (ECLIPSE data)	453.4	458.0	0.091	0.055	−£1105	Dominant	0.175	0.204	−£1749	Dominant
6MWD lower CI (ECLIPSE data)	385.3	379.9	0.090	0.055	−£1107	Dominant	0.174	0.204	−£1751	Dominant
6MWD upper CI (ECLIPSE data)	385.3	390.7	0.090	0.055	−£691	Dominant	0.174	0.204	−£1337	Dominant
mMRC −25%	39.9%	29.9%	0.089	0.054	−£696	Dominant	0.172	0.203	−£1349	Dominant
mMRC +25%	39.9%	49.9%	0.091	0.055	−£1100	Dominant	0.176	0.204	−£1739	Dominant
FEV1 lower CI	70	45	0.058	0.038	−£221	Dominant	0.143	0.187	−£934	Dominant
FEV1 upper CI	70	95	0.122	0.071	−£1125	Dominant	0.204	0.220	−£1707	Dominant
SGRQ lower CI^a	−0.11	−1.66	0.090	0.163	−£690	Dominant	0.174	0.310	−£1336	Dominant
SGRQ upper CI^a	−0.11	1.43	0.090	−0.056	−£690	£12,284	0.174	0.095	−£1336	Dominant

Notes: ^aConverted to SGRQ-C score using a revised version of the SGRQ questionnaire and scoring system as previously described.^20,36

Abbreviations: 6MWD, 6-minute walk distance; CI, confidence interval; FEV₁, forced expiratory volume in 1 second; ICER, incremental cost-effectiveness ratio; ITT, intent-to-treat; LY, life-year; mMRC, modified Medical Research Council dyspnea scale; QALY, quality-adjusted life-year; SAL, salmeterol; SGRQ, St George’s Respiratory Questionnaire; UMEC, umeclidinium; VI, vilanterol.

Figure 2 Probabilistic sensitivity analysis of incremental cost-effectiveness with (A) UMEC/VI versus UMEC and (B) UMEC/VI versus SAL, showing incremental differences between costs and QALYs between treatments over 5000 Monte Carlo simulations where distributions of input parameters were assigned and sampled randomly. Red circles indicate the base case results.

Abbreviations: QALY, quality-adjusted life-year; SAL, salmeterol; UMEC, umeclidinium; VI, vilanterol.

Figure 3 Net benefit acceptability curves for with (A) UMEC/VI versus UMEC and (B) UMEC/VI versus SAL, showing the relative probability of cost-effectiveness across the range of £0–45,000 per QALY for competing treatments included in the model. The dashed vertical line indicates the willingness-to-pay threshold at £20,000.

Abbreviations: SAL, salmeterol; UMEC, umeclidinium; VI, vilanterol.

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