M. Najafzadeh, C. A. Marra, M. Sadatsafavi, S. D. Aaron, S. D. Sullivan, K. L. Vandemheen, P. W. Jones, and J. M. FitzGerald. Cost effectiveness of therapy with combinations of long acting bronchodilators and inhaled steroids for treatment of COPD. Thorax 63 (11):962-967, 2008. Ref ID: 2588

Study detailsPopulation & interventionsHealth outcomesCostsCost effectiveness
Economic analysis:
CEA/CUA

Study design:
Within RCT analysis (OPTIMAL10)

Perspective:
Canadian NHS

Time horizon:
1 year

Discounting:
N/a
Population:
COPD patients (FEV1<65% predicted)
N=449

Intervention 1:
Tiotropium 18μg once daily (LAMA)

Intervention 2:
Tiotropium 18μg once daily + salmeterol 25μg ×2 puffs, twice daily (LAMA+ LABA)

Intervention 3:
Tiotropium18μg once daily + salmeterol/ fluticasone propionate 25μg/250μg ×2 puffs twice daily (LAMA+LABA+ICS)
Health outcomes incorporated:
Exacerbations, life years, quality of life

Primary outcome measure:
Exacerbations (mean/year)
  1. LAMA: 1.56 (CI: 1.34-1.81)
  2. LAMA+LABA: 1.69 (CI:1.47-1.94)
  3. LAMA+LABA+ICS: 1.35 (CI : 1.16-1.55)
Incremental (not reported; calculated from above):
Intvn 2 – 1: 0.13 (CI: NR)
Intvn 3 – 1: -0.21 (CI:NR)

Other outcome measures:
QALYs (mean)
  1. LAMA: 0.7092 (CI: 0.6953, 0.7228)
  2. LAMA+LABA: 0.7124 (CI : 0.6931, 0.7310)
  3. LAMA+LABA+ICS: 0.7217 (CI : 0.7034, 0.7389)
Incremental (adjusted for baseline utility):
Intvn 2 – 1: -0.0052 (CI : -0.0088, 0.0032)
Intvn 3 – 1: 0.0056 (CI : -0.0142, 0.0251)
Intvn 3 – 2: NR (not possible to calc due to adjustment of QALYs in incremental analysis)
Cost components incorporated:
Study drugs, exacerbation related medications, nursing and respiratory care visits at home, physician and ER visits, and hospital or ICU admissions. Non-COPD hospitalisations were included in a sensitivity analysis.

Total costs (mean):
  1. LAMA: £1435 (CI: £1045, £1895)
  2. LAMA+LABA: £1501 (CI: £1236, £1802)
  3. LAMA+LABA+ICS: £2166 (CI: £1730, £2676)
Incremental (not reported; calculated from above):
Intvn 2 – 1: £66 (CI: NR)
Intvn 3 – 1: £731 (CI: NR)
Intvn 3 – 2: £665 (CI: NR)

Currency & cost year:
2006 Canadian Dollars (presented here as 2006 UK pounds)
Base case ICERs:
Cost/exacerbation avoidedCI
Intvn 2-1:LAMA dominantNR
Intvn 3-1:£3488Graphically only
Intvn 3-2:NRNR
Cost/QALY gainedCI
Intvn 2-1:LAMA dominantNR
Intvn 3-1:£130,308Graphically only
Intvn 3-2:NRn/a
Analysis of uncertainty
From bootstrap/imputation analysis for Intvn 3 vs 1 (triple vs LAMA) LAMA was cost-effective in >90% of simulations at a threshold of £20,000/QALY. Not reported for other comparisons.
Various one way sensitivity analyses undertaken including looking at complete cases only, including non-COPD hospitalisations, FEV1≤50% predicted only, 50% <FEV1 <65% predicted, attributing disutility during exacerbation, excluding cost of patient with 215 day hospital stay in triple arm. Conclusions were maintained except in the analysis of FEV1≤50% predicted only where LABA+LAMA became a cost-effective option compared to LAMA alone. Range £13,655-dominated for LAMA+LABA vs LAMA. Range £30,620-£78,103 for triple vs LAMA.
Data sources
Health outcomes: patient level data from Optimal study
Quality-of-life weights: EQ5D calculated from patient level SGRQ data from Optimal study using published algorithm. Tariff unclear.
Cost sources: Patient level resource use prospectively collected during Optimal study. Drugs based on Canadian national reimbursement rates; hospitalisation costs from Vancouver hospital; ER visit from literature; others from fee-for-service rates of British Columbia Medical Services Plan.
Comments
Source of funding: National Sanitarium Association, Canadian Institutes of Health Research.
Limitations: There is some uncertainty over the applicability of Canadian costs and resource use data to the UK. Key limitations: GDG concerns re clinical trial; LABA+ICS drug costs based on 250/50 inhaler ×2 puffs, twice daily – in UK this would cost £260 more than using the 500/50 inhaler ×1puff, twice daily (not included in sensitivity analysis); one patient in triple arm had a 215 day hosp stay (included in base case although excluded in a sensitivity analysis); in base case QALYs based on SGRQ differences mapped to EQ5D. Minor limitations: Resource use may be influenced by trial setting. Time horizon is 1 year – investigations of impact of longer term extrapolation may be appropriate – authors consider this unlikely to impact results greatly.
Overall quality*: Potentially serious limitationsOverall applicability**: Partially applicable

Abbreviations: CI = confidence interval; COPD = chronic obstructive pulmonary disorder; CUA = cost-utility analysis; ER = emergency room; ICER = incremental cost-effectiveness ratio; ICU = intensive care unit; NR = not reported; QALY = quality-adjusted life-year;

Converted using 2006 Purchasing Power Parities4;

*

Very serious limitations / Potentially serious Limitations / Minor limitations;

**

Directly applicable / Partially applicable / Not applicable

From: Appendix F, Evidence tables

Cover of Chronic Obstructive Pulmonary Disease
Chronic Obstructive Pulmonary Disease: Management of Chronic Obstructive Pulmonary Disease in Adults in Primary and Secondary Care [Internet].
NICE Clinical Guidelines, No. 101.
National Clinical Guideline Centre (UK).
Copyright © 2010, National Clinical Guideline Centre - Acute and Chronic Conditions.

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