Cost-effectiveness of combination therapy umeclidinium/vilanterol versus tiotropium in symptomatic COPD Spanish patients

Figures & data

Table 1 Baseline characteristics of the population included in the analysis

Baseline characteristics	Base case	Source
Sex
Female (%)	17	Casanova et al^Citation19
Male (%)	83
Mean age (years)	67	Casanova et al^Citation19
Body mass index
Low (%)	4.6	Casanova et al^Citation19
Medium (%)	60.3
High (%)	35.1
≥1 cardiovascular comorbidity (%)	29	Maleki-Yazdi et al^Citation22
≥1 other comorbidity (%)	86
History of exacerbations, ≥1 (%)	16.6
mMRC score ≥2 (%)	100
Active smokers (%)	29	Casanova et al^Citation19
Height (m) (mean)	1.676	Spanish National Health Survey^Citation21
Fibrinogen (μg/mL) (mean)	458.8	Vestbo et al^Citation14 Agusti et al^Citation15
Number of exacerbations in previous year (mean)	0.27	Maleki-Yazdi et al^Citation22
Moderate/severe ratio	80:20	Hurst et al^Citation44
SGRQ score (mean)	42.7	Almagro et al^Citation20
Post-bronchodilator baseline FEV1 (%pred) (mean)	46.4%	Maleki-Yazdi et al^Citation22
Six-minute walk test (6MWT) (m) (mean)	438	Casanova et al^Citation19

Abbreviations: mMRC, modified Medical Research Council; SGRQ, St George’s Respiratory Questionnaire; FEV₁, forced expiratory volume in 1 second.

Table 2 Risk equation to incorporate Spanish utilities (linear regression model)

Variables	Effect
Intercept	0.8345
Female (vs male)	−0.0875
Low BMI (vs mean)	−0.0059
High BMI (vs mean)	-0.0136
Cardiovascular comorbidities (vs no)	−0.0074
Other comorbidities (vs no)	−0.0074
Smoker (vs ex-smoker)	−0.0244
Age	0.0012
Number of exacerbations	−0.0291
Post-bronchodilator FEV1 (%pred)	0.0006
mMRC 2–3 (vs 0–1)	−0.1541
mMRC 4 (vs 0–1)	−0.5326
Cough and sputum (vs no)a	−0.0672

Note:

a Defined as answers ≥3 in the first two dimensions of the CAT (COPD Assessment Test) questionnaire.

Abbreviations: BMI, body mass index; FEV₁, forced expiratory volume in 1 second; pred, predicted; mMRC, modified Medical Research Council.

Table 3 Unitary costs of health care resources included in the analysis

Type	Cost (€)	Source
Drug cost (PTP + VAT)
UMEC/VI – 55/22 umeclidinium/vilanterol powder for inhalation 30 doses	70.25	National Formulary
TIO – 18 μg tiotropium powder for inhalation 30 capsules	49.06	Listing^Citation27
Cost per episode of exacerbation
Moderate exacerbation	70.86	Miravitlles et al^Citation28,Citation29
Severe exacerbation	4,349.61
Annual cost of management according to symptoms
Dyspnea level 1: no symptoms per week = mMRC 0–1	511.18	Punekar et al^Citation30
Dyspnea stage 2: symptoms several days per week = mMRC 2–3	681.72	Almagro et al^Citation20
Dyspnea level 3: symptoms nearly every day = mMRC 4	901.7	Sicras et al^Citation31

Abbreviations: PTP + VAT, retail price plus value added tax; UMEC/VI, umeclidinium and vilanterol; TIO, tiotropium; mMRC, modified Medical Research Council.

Table 4 Deterministic sensitivity analysis values

Parameter	Base case	Alternative values
Time horizon	3 years	1 year, 5 years
Baseline characteristics	Spanish population data, clinical development of UMEC/VI and ECLIPSE	Clinical development UMEC/VI and ECLIPSE
Efficacy data UMEC/VI vs TIO	112 mL (81.144; P<0.001) (Maleki-Yazdi et al^Citation22)	60 mL (10.109; P=0.018) (Decramer et al^Citation33)
Duration of efficacy	First year	First 6 months Entire time horizon (3 years)
Modeling of quality of life	Spanish utilities (M1)	SGRQ
Discount rate for costs and future events	3%	(0%–5%)
Exacerbation unitary cost (moderate and severe)	Estimated from Miravitlles et al^Citation28,Citation29	(± 20%)
Follow-up cost according dyspnea levels (three levels of frequency)	Estimated from Sicras et al^Citation31	(±20%)
	Punekar et al^Citation30
	Almagro et al^Citation20

Abbreviations: UMEC/VI, umeclidinium and vilanterol; TIO, tiotropium; SGRQ, St George’s Respiratory Questionnaire; ECLIPSE, Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points.

Table 5 Results of base case

	UMEC/VI		TIO
Health outcomes (QALY)	2.025		1.998
Costs	€6,215		€5,625
ICER (€/QALY)		€21,475

Abbreviations: UMEC/VI, umeclidinium and vilanterol; TIO, tiotropium; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life year.

Figure 1 Results of the sensitivity analysis.

Abbreviations: SGRQ, St George’s Respiratory Questionnaire; UMEC/VI, umeclidinium and vilanterol; TIO, tiotropium; Min, minimum; Max, maximum.

Figure 2 Probabilistic sensitivity analysis results. Cost-effectiveness plane.

Abbreviations: QALYs, quality-adjusted life years; UMEC/VI, umeclidinium and vilanterol; TIO, tiotropium.

Figure 3 Acceptability curve.

Abbreviations: QALY, quality-adjusted life year; UMEC/VIL, umeclidinium/vilanterol.

Table S1 Risk equations developed for utility estimation

Risk equation	Scenario	Description
M1	Base case	Saturated linear regression model
M2	Sensitivity analysis	Reduction in number of variables according to goodness of fit index AIC
M3	Sensitivity analysis	Grouping of frequency and severity of dyspnea: mMRC2 (vs 0–1) and mMRC3–4 (vs 0–1)
M4	Sensitivity analysis	Variable cough and sputum = score ≥2 in first two items of CAT
M5	Sensitivity analysis	Variable cough and sputum = score ≥4 in first two items of CAT

Abbreviations: AIC, Akaike information criterion; mMRC, modified Medical Research Council; CAT, COPD Assessment Test.

Table S2 Variables considered in each of the risk equations

	Base-case sensitivity analysis
	Effect
	M1	M2	M3	M4	M5
Intercept	0.8345	0.9158	0.8526	0.8345	0.8148
Female (vs male)	−0.0875	−0.0902	−0.0819	−0.0875	−0.0749
Low BMI (vs mean)	−0.0059	–	−0.0870	−0.0059	−0.0153
High BMI (vs mean)	−0.0136	–	−0.0305	−0.0136	−0.0197
Cardiovascular comorbidities (vs no)	−0.0074	–	−0.0407	−0.0074	−0.0023
Other comorbidities (vs no)	−0.0074	–	−0.0169	−0.0074	−0.0091
Smoker (vs ex-smoker)	−0.0244	–	−0.0488	−0.0244	−0.0338
Age	0.0012	–	0.0012	0.0012	0.0010
Number of exacerbations	−0.0291	−0.0298	−0.0338	−0.0291	−0.0316
FEV1 (%) post-bronchodilator	0.0006	–	0.0004	0.0006	0.0008
mMRC 2–3 (vs 0–1)a	−0.1541	−0.1606	−0.1089	−0.1541	−0.1573
mMRC 4 (vs 0–1)a	−0.5326	−0.5390	−0.3041	−0.5326	−0.5275
Cough and sputum (vs no)b	−0.0672	−0.0581	−0.0600	−0.0672	−0.0776

Notes:

a In M3, grouping is mMRC 2 (vs 0–1) and mMRC 3–4 (vs 0–1).

b In M4 and M5, cough and sputum are considered as equivalent to the score in the first two items of CAT ≥2 and ≥4, respectively.

Abbreviations: BMI, body mass index; FEV₁, forced expiratory volume in 1 second; mMRC, modified Medical Research Council; –, variable not considered in the model.

Table S3 Results obtained considering risk equations developed for utility estimation

	UMEC/VI		TIO		UMEC/VI vs TIO
	QALY	Cost (€)	QALY	Cost (€)	ΔQALY	ΔCost (€)	ICER (€/QALY)
Base case
M1	2.025	6,215	1.998	5,625	+0.0275	+590.1	21,475
M2	2.043	6,215	2.039	5,625	+0.0048	+590.1	123,425
M3	2.021	6,215	1.994	5,625	+0.0271	+590.1	21,794
M4	2.028	6,215	1.999	5,625	+0.0288	+590.1	20,456
M5	2.024	6,215	1.997	5,625	+0.0271	+590.1	21,759

Abbreviations: UMEC/VI, umeclidinium and vilanterol; TIO, tiotropium; QALY, quality-adjusted life years; ICER, incremental cost-effectiveness ratio.

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