Cost-Effectiveness Of Once-Daily Single-Inhaler Triple Therapy In COPD: The IMPACT Trial

Figures & data

Figure 1 Linked-risk equation model. Blue lines indicate the relationship between the central attributes in the different time periods. Orange lines indicate the relationship between intermediate outcomes and exacerbations. Black lines indicate the relationship between the central attributes and the final health outcomes. Adapted from Briggs AH, Baker T, Risebrough NA, et al (2017). Development of the Galaxy Chronic Obstructive Pulmonary Disease (COPD) Model Using Data from ECLIPSE: Internal Validation of a Linked-Equations Cohort Model Med Decis Making, 37(4): 469–480. https://doi.org/10.1177/0272989X16653118. Copyright © 2017 by the authors. Reprinted by permission of SAGE Publications, Inc.¹¹ *Calculated (in mL) using the risk equation at 1 year and converted to FEV₁% predicted based on the cohort profile.

Abbreviations: 6MWT, 6-min walk test; FEV₁, forced expiratory volume in 1 s; LY, life year; QALY, quality-adjusted life year; RU, resource utilization; SGRQ, St. George’s Respiratory Questionnaire.

Table 1 Summary Of Model Inputs

Parameters	Reference Estimate	Probability Distribution	Source
Baseline characteristics
Female, %	34	Fixed	IMPACT Trial Supplementary Materials (GSK, 2017)
Mean age, years	65.3	Fixed	IMPACT Trial Supplementary Materials (GSK, 2017)
Current smoker, %	35	Fixed	IMPACT Trial Supplementary Materials (GSK, 2017)
Any CV comorbidity, %	44	Fixed	IMPACT Trial Supplementary Materials (GSK, 2017)
Any other comorbidity, %	57	Fixed	IMPACT Trial Supplementary Materials (GSK, 2017)
History of ≥1 exacerbation in the previous year, %	100	Fixed	IMPACT Trial Supplementary Materials (GSK, 2017)
BMI (kg/m^2), %
BMI <21	17	Fixed	IMPACT Trial Supplementary Materials (GSK, 2017)
BMI 21–30	58	Fixed	IMPACT Trial Supplementary Materials (GSK, 2017)
BMI >30	25	Fixed	IMPACT Trial Supplementary Materials (GSK, 2017)
Dyspnea, %
None	1.7	Fixed	Derived from a risk equation
Several days/week	32.9	Fixed	Derived from a risk equation
Most days/week	65.4	Fixed	Derived from a risk equation
Cough or sputum, most days/week, %	52.2	Fixed	Derived from a risk equation
Exacerbations in prior year (mean), n
Total	1.71	Fixed	IMPACT Trial Supplementary Materials (GSK, 2017)
Moderate	1.41	Fixed	IMPACT Trial Supplementary Materials (GSK, 2017)
Severe	0.30	Fixed	IMPACT Trial Supplementary Materials (GSK, 2017)
Starting FEV1% predicted	45.5	Fixed	IMPACT Trial Supplementary Materials (GSK, 2017)
Starting FEV1 predicted by the GALAXY model, mL	1215.3	Fixed	Based on FEV1% reported in IMPACT and formulae based in ECLIPSE to back calculate the starting FEV1 value
Height, cm	167.5	Fixed	IMPACT Trial Supplementary Materials (GSK, 2017)
mMRC dyspnea score ≥2, %	37	Fixed	% with CAT score ≥21 from IMPACT considered equivalent; IMPACT Trial Supplementary Materials (GSK, 2017)
Fibrinogen, μg/dL	477.5	Fixed	Not available from IMPACT, derived from a risk equation
6MWT, m	365.8	Fixed	Not available from IMPACT, derived from a risk equation
Mean starting SGRQ total score	50.7	Fixed	IMPACT Trial Supplementary Materials (GSK, 2017)
Resulting HRQoL utility value	0.654	Fixed	Calculated from SGRQ-C score by algorithm^Citation19
Treatment effects
FF/UMEC/VI versus FF/VI
Difference FEV1 incremental change from baseline, mL	97	Normal (SE=6.10)	IMPACT Trial Supplementary Materials (GSK, 2017)
Difference SGRQ total score change from baseline	−1.8	Normal (SE=0.34)	IMPACT Trial Supplementary Materials (GSK, 2017), converted to SGRQ-C
Moderate exacerbation reduction, ratio	0.84	Log normal (SE=0.03)	IMPACT Trial Supplementary Materials (GSK, 2017)
Severe exacerbation reduction, ratio	0.87	Log normal (SE=0.06)	IMPACT Trial Supplementary Materials (GSK, 2017)
FF/UMEC/VI versus UMEC/VI
Difference FEV1 incremental change from baseline, mL	54	Normal (SE=7.60)	IMPACT Trial Supplementary Materials (GSK, 2017)
Difference SGRQ total score change from baseline	−1.8	Normal (SE=0.42)	IMPACT Trial Supplementary Materials (GSK, 2017), converted to SGRQ-C
Moderate exacerbation reduction, ratio	0.77	Log normal (SE=0.03)	IMPACT Trial Supplementary Materials (GSK, 2017)
Severe exacerbation reduction, ratio	0.66	Log normal (SE=0.06)	IMPACT Trial Supplementary Materials (GSK, 2017)
Treatment discontinuation at 52 weeks
FF/UMEC/VI	18.3%	Beta (758/4151)	IMPACT Trial Supplementary Materials (GSK, 2017)
FF/VI	25.2%	Beta (1040/4134)	IMPACT Trial Supplementary Materials (GSK, 2017)
UMEC/VI	27.3%	Beta (566/2070)	IMPACT Trial Supplementary Materials (GSK, 2017)
Drug costs	Cost per day
FF/UMEC/VI (100/62.5/25 μg) (Trelegy ELLIPTA)	C$4.41	Fixed	Assume same as price for FF/VI + UMEC
UMEC (62.5 μg) (Incruse ELLIPTA)	C$1.67	Fixed	ODB, 2017^Citation20
FF/VI (100/25 μg) (Breo ELLIPTA)	C$2.74	Fixed	ODB, 2017^Citation20
UMEC/VI (62.5/25 μg) (Anoro ELLIPTA)	C$2.70	Fixed	ODB, 2017^Citation20
Subsequent treatment cost
Average weighted cost of all treatment classes	C$4.29	Fixed	Average cost weighted by Canadian prescription utilization in regimen class (based on IMS data)^Citation21
Outpatient medication
Cost of moderate exacerbations	C$7.59	Fixed	Calculation based on ODB, 2017^Citation20
Rescue medication	Cost per day
Salbutamol (Ventolin DISKUS)	C$0.03	Fixed	ODB, 2017^Citation20
Occasions of rescue medication use per day
FF/UMEC/VI	1.75	Fixed	IMPACT Trial Supplementary Materials (GSK, 2017)
FF/VI	2.03	Fixed	IMPACT Trial Supplementary Materials (GSK, 2017)
UMEC/VI	2.05	Fixed	IMPACT Trial Supplementary Materials (GSK, 2017)
Hospital costs
Cost per day in ICU	C$3843.40	Fixed	CIHI, 2016^Citation22 OHIP, 2016^Citation23 Statistics Canada, 2017^Citation24
Cost per day in general ward	C$1256.30	Fixed	CIHI, 2016^Citation22 Statistics Canada, 2017^Citation24
ER visit	C$76.90	Fixed	OHIP, 2016^Citation23
Hospital outpatient visit – initial visit	C$157.00	Fixed	OHIP, 2016^Citation23
Physician costs
Day(/night) home visit^#	C$45.15	Fixed	OHIP, 2016^Citation23
Visit to physician’s office (family physician)	C$77.20	Fixed	OHIP, 2016^Citation23
Telephone consultation^¶	C$9.30	Fixed	OHIP, 2016^Citation23 Statistics Canada, 2017^Citation24 Payscale, 2017^Citation25

Notes: The IMPACT Trial Supplementary Materials are GlaxoSmithKline plc. internal data on file (Nov/Dec 2017). ^#The model assumes the same cost for home consultations whether they occur during “day” or “night” hours; OHIP 2016 schedule reports billing rates current in 2017. ^¶The cost of a telephone call is based on assuming the interaction is 10 min in length and a nurse (registered nurse hourly wage C$33.01) will take the call 60% of the time and a physician the remaining 40%. Physician code H101 (C$15.00) was selected as a substitute value since there is no appropriate code for a telephone call between a patient and physician.

Abbreviations: 6MWT, 6-min walk test; BMI, body mass index; CAT, COPD Assessment Test; CIHI, Canadian Institute for Health Information; CV, cardiovascular; C$, Canadian dollars; ER, emergency room; FEV₁, forced expiratory volume in 1 s; FF, fluticasone furoate; HRQoL, health-related quality of life; ICU, intensive care unit; IMS, IMS Brogan ODB RxDynamics Database; mMRC, modified Medical Research Council; ODB, Ontario Drug Benefit; OHIP, Ontario Health Insurance Program; SE, standard error; SGRQ, St. George’s Respiratory Questionnaire; SGRQ-C, St. George’s Respiratory Questionnaire for COPD patients; UMEC, umeclidinium; VI, vilanterol.

Table 2 Cumulative And Incremental Lifetime Outcomes Of FF/UMEC/VI Versus FF/VI

	FF/UMEC/VI		FF/VI	Difference
Cumulative exacerbations
Moderate exacerbations	10.6200		11.2337	−0.6136
Severe exacerbations	3.5326		3.6314	−0.0988
Total exacerbations (moderate and severe)	14.1526		14.8650	−0.7124
Moderate exacerbations PPPY	1.1728		1.2605	−0.0878
Severe exacerbations PPPY	0.3884		0.4056	−0.0172
Total exacerbations PPPY	1.5611		1.6661	−0.1050
Health outcomes
Accumulated LYs (undiscounted)	9.0524		8.9136	0.1388
Accumulated QALYs	5.0431		4.9060	0.1371
Costs
Drug costs	C$13,387		C$11,461	C$1926
Total non-drug costs	C$53,750		C$53,072	C$678
Hospital (ICU and ward) costs	C$52,506		C$51,835	C$672
Outpatient/ER costs	C$651		C$646	C$5.38
Physician visit costs	C$592		C$591	C$0.96
Accumulated costs total	C$67,137		C$64,533	C$2604
Incremental results
Incremental costs (95% CI)	C$2604	(C$1980, C$3285)
Incremental LYs (95% CI) undiscounted	0.1388	(0.068, 0.207)
Incremental QALYs (95% CI)	0.1371	(0.092, 0.182)
ICER/QALY gained (95% CI)	C$18,989	(C$14,665, C$25,753)

Abbreviations: CI, confidence interval; C$, Canadian dollars; ER, emergency room; FF, fluticasone furoate; ICER, incremental cost-effectiveness ratio; ICU, intensive care unit; LY, life year; QALY, quality-adjusted life year; PPPY, per patient per year; UMEC, umeclidinium; VI, vilanterol.

Figure 2 Incremental cost-effectiveness plane for FF/UMEC/VI versus FF/VI (A), and tornado plot of sensitivity and scenario analyses (B). *Assume 100% market share of product.

Abbreviations: 6MWT, 6-min walk test; CI, confidence interval; COPD, chronic obstructive pulmonary disease; C$, Canadian dollars; DPI, dry-powder inhaler; FF, fluticasone furoate; FP, fluticasone propionate; ICER, incremental cost-effectiveness ratio; ICS, inhaled corticosteroid; ITT, intent to treat; LABA, long-acting β₂-agonist; mMRC, modified Medical Research Council; PSA, probabilistic sensitivity analysis; QALY, quality-adjusted life year; SAL, salmeterol; SITT, single-inhaler triple therapy; UMEC, umeclidinium; VI, vilanterol.

Figure 3 Net benefit acceptability curves for FF/UMEC/VI versus FF/VI.

Abbreviations: C$, Canadian dollars; FF, fluticasone furoate; QALY, quality-adjusted life year; UMEC, umeclidinium; VI, vilanterol.

Table 3 Cumulative And Incremental Lifetime Outcomes Of FF/UMEC/VI Versus FF/VI

	FF/UMEC/VI		UMEC/VI	Difference
Cumulative exacerbations
Moderate exacerbations	10.2638		11.2357	−0.9719
Severe exacerbations	3.2631		3.6314	−0.3683
Total exacerbations (moderate and severe)	13.5269		14.8671	−1.3402
Moderate exacerbations PPPY	1.1364		1.2615	−0.1251
Severe exacerbations PPPY	0.3593		0.4056	−0.0464
Total exacerbations PPPY	1.4957		1.6671	−0.1714
Health outcomes
Accumulated LYs (undiscounted)	9.0258		8.9081	0.1177
Accumulated QALYs	5.0352		4.9070	0.1282
Costs
Drug costs	C$13,346		C$11,519	C$1827
Total non-drug costs	C$53,065		C$53,126	−C$61
Hospital (ICU and ward) costs	C$51,830		C$51,887	−C$58
Outpatient/ER costs	C$645		C$646	−C$0.72
Physician visit costs	C$589		C$592	−C$2.67
Accumulated costs total	C$66,411		C$64,644	C$1766
Incremental results
Incremental costs (95% CI)	C$1766	(C$1167, C$2336)
Incremental LYs (95% CI) undiscounted	0.1177	(0.048, 0.186)
Incremental QALYs (95% CI)	0.1282	(0.081, 0.177)
ICER/QALY gained (95% CI)	C$13,776	(C$9787, C$19,448)

Abbreviations: CI, confidence interval; C$, Canadian dollars; ER, emergency room; FF, fluticasone furoate; ICER, incremental cost-effectiveness ratio; ICU, intensive care unit; LY, life year; QALY, quality-adjusted life year; PPPY, per patient per year; UMEC, umeclidinium; VI, vilanterol.

Figure 4 Incremental cost-effectiveness plane for FF/UMEC/VI versus UMEC/VI (A), and tornado plot of sensitivity and scenario analyses (B). *Assume 100% market share of product.

Abbreviations: 6MWT, 6-min walk test; CI, confidence interval; COPD, chronic obstructive pulmonary disease; C$, Canadian dollars; DPI, dry-powder inhaler; FF, fluticasone furoate; FP, fluticasone propionate; ICER, incremental cost-effectiveness ratio; ITT, intent to treat; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; mMRC, modified Medical Research Council; PSA, probabilistic sensitivity analysis; QALY, quality-adjusted life year; SAL, salmeterol; SITT, single-inhaler triple therapy; UMEC, umeclidinium; VI, vilanterol.

Figure 5 Net benefit acceptability curves for FF/UMEC/VI versus UMEC/VI.

Abbreviations: C$, Canadian dollars; FF, fluticasone furoate; QALY, quality-adjusted life year; UMEC, umeclidinium; VI, vilanterol.

Briggs AH, Baker T, Risebrough NA, et al. Development of the Galaxy Chronic Obstructive Pulmonary Disease (COPD) model using data from ECLIPSE: internal validation of a linked-equations cohort model. Med Decis Making. 2017;37:469–480. doi:10.1177/0272989X1665311827317436

 PubMed Web of Science ®Google Scholar

Starkie HJ, Briggs AH, Chambers MG, et al. Predicting EQ-5D values using the SGRQ. Value Health. 2011;14:354–360. doi:10.1016/j.jval.2010.09.01121402304

 PubMed Web of Science ®Google Scholar

Ontario Drug Benefit Formulary. Comparative drug index (effective December 2017). Available from: https://www.formulary.health.gov.on.ca/formulary/ Accessed 114, 2019.

 Google Scholar

IMS Brogan. ODB RxDynamics® Database. Respiratory Therapies 2017 [data on file].

 Google Scholar

Canadian Institute for Health Information (CIHI). Care in Canadian ICUs. 2016 Available from: https://www.cihi.ca/en/ICU_DataTables_EN.xlsx Accessed 114, 2019.

 Google Scholar

Ontario Health Insurance Plan (OHIP) – Schedule of benefits. 2016 Available from: http://www.health.gov.on.ca/en/pro/programs/ohip/sob/ Accessed 114, 2019.

 Google Scholar

Statistics Canada. Consumer price index. 2017 Available from: http://statcan.gc.ca/tables-tableaux/sum-som/l01/cst01/cpis01a-eng.htm Accessed 114, 2019.

 Google Scholar

Payscale. Registered Nurse wage. 2017 Available from: http://www.payscale.com Accessed 114, 2019.

 Google Scholar