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:

Study design:
Within RCT analysis (OPTIMAL10)

Canadian NHS

Time horizon:
1 year

COPD patients (FEV1<65% predicted)

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.
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.

Apart from any fair dealing for the purposes of research or private study, criticism or review, as permitted under the Copyright, Designs and Patents Act, 1988, no part of this publication may be reproduced, stored or transmitted in any form or by any means, without the prior written permission of the publisher or, in the case of reprographic reproduction, in accordance with the terms of licences issued by the Copyright Licensing Agency in the UK. Enquiries concerning reproduction outside the terms stated here should be sent to the publisher at the UK address printed on this page. The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant laws and regulations and therefore for general use. The rights of National Clinical Guideline Centre to be identified as Author of this work have been asserted by them in accordance with the Copyright, Designs and Patents Act, 1988.

PubMed Health. A service of the National Library of Medicine, National Institutes of Health.