|
 |
|
|||||||
|
|||||||||
Copyright ©ERS Journals Ltd 2004
Inhaled steroids and mortality in COPD: bias from unaccounted immortal time
Division of Clinical Epidemiology, Royal Victoria Hospital, McGill University Health Centre, and the Depts of Epidemiology and Biostatistics and of Medicine, McGill University, Montreal, Canada
CORRESPONDENCE: S. Suissa, Division of Clinical Epidemiology, Royal Victoria Hospital, 687 Pine Avenue West, Ross 4.29, Montreal, Canada, H3A 1A1. Fax: 1 5148431493. E-mail: samy.suissa@clinepi.mcgill.ca
Keywords: biases, cohort studies, drug effectiveness, epidemiology, immortal time, pharmacoepidemiology
Received: June 3, 2003
Accepted October 5, 2003
This research was funded by grants from the Canadian Institutes of Health Research (CIHR) and Fonds de la recherche en Santé du Québec (FRSQ). The acquisition of the database was funded by grants from AstraZeneca, Boehringer Ingelheim and GlaxoSmithKline. The author is the recipient of a Distinguished Investigator award from the CIHR. This study is based on de-identified data provided by the Saskatchewan Dept of Health. The interpretation and conclusions contained herein do not necessarily represent those of the government of Saskatchewan or the Saskatchewan Dept of Health.
A recent observational study, which suggested that inhaled corticosteroids (ICS) with or without long-acting bronchodilators are effective at reducing all-cause mortality in chronic obstructive pulmonary disease (COPD) patients, may be subject to immortal time bias.
This bias was assessed using a population-based cohort of 3,524 newly treated COPD patients from Saskatchewan, Canada, observed from 1990–1999. Regular users of bronchodilators or ICS were followed for 3 yrs, during which time 860 deaths occurred. Cox's proportional hazards model was used to compare the hierarchical intention-to-treat approach employed in the recent study, a technique subject to bias from two sources of immortal time, with the conventional intention-to-treat approach and the according-to-treatment approach.
The adjusted rate ratio of death using the hierarchical intention-to-treat approach was 0.66 (95% confidence interval (CI) 0.57–0.76) for ICS use relative to bronchodilator use, compared with 0.75 (95% CI 0.62–0.90) with the conventional intention-to-treat approach. Conversely, the rate ratio was 0.94 (95% CI 0.81–1.09) with the according-to-treatment approach, which accounts for both sources of immortal time.
In this study, regular inhaled corticosteroid use in chronic obstructive pulmonary disease was not found to reduce all-cause mortality. Suggestion of this benefit from a previous observational study is the result of bias from unaccounted immortal time in its cohort design and analysis.
This article has been cited by other articles:
|
|
 |
|
  S. Suissa and P. J. Barnes Inhaled corticosteroids in COPD: the case against Eur. Respir. J., July 1, 2009; 34(1): 13 - 16. [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Falk, O. A. Minai, and Z. Mosenifar Inhaled and Systemic Corticosteroids in Chronic Obstructive Pulmonary Disease Proceedings of the ATS, May 1, 2008; 5(4): 506 - 512. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Sridhar, R Taylor, S Dawson, N J Roberts, and M R Partridge A nurse led intermediate care package in patients who have been hospitalised with an acute exacerbation of chronic obstructive pulmonary disease Thorax, March 1, 2008; 63(3): 194 - 200. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Suissa Immortal Time Bias in Pharmacoepidemiology Am. J. Epidemiol., February 15, 2008; 167(4): 492 - 499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Suissa, R. McGhan, D. Niewoehner, and B. Make Inhaled Corticosteroids in Chronic Obstructive Pulmonary Disease Proceedings of the ATS, October 1, 2007; 4(7): 535 - 542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Mikaeloff, G. Caridade, S. Assi, M. Tardieu, S. Suissa, and on behalf of the KIDSEP study group of the French Hepatitis B vaccine and risk of relapse after a first childhood episode of CNS inflammatory demyelination Brain, April 1, 2007; 130(4): 1105 - 1110. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Suissa Statin Use and Risks for Death and Hospitalization in Chronic Heart Failure JAMA, March 14, 2007; 297(10): 1057 - 1057. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Setoguchi, R. J. Glynn, J. Avorn, H. Mogun, and S. Schneeweiss Statins and the Risk of Lung, Breast, and Colorectal Cancer in the Elderly Circulation, January 2, 2007; 115(1): 27 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Macie, K. Wooldrage, J. Manfreda, and N. R. Anthonisen Inhaled Corticosteroids and Mortality in COPD. Chest, September 1, 2006; 130(3): 640 - 646. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Suissa Observational Studies of Inhaled Corticosteroids in Chronic Obstructive Pulmonary Disease: Misconstrued Immortal Time Bias Am. J. Respir. Crit. Care Med., February 15, 2006; 173(4): 464 - 464. [Full Text] [PDF]
|
|
|
|
|
|
J. F. Donohue Combination Therapy for Chronic Obstructive Pulmonary Disease: Clinical Aspects Proceedings of the ATS, November 1, 2005; 2(4): 272 - 281. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Samet Inhaled Corticosteroids and Chronic Obstructive Pulmonary Disease: New and Improved Evidence? Am. J. Respir. Crit. Care Med., August 15, 2005; 172(4): 407 - 408. [Full Text] [PDF]
|
|
|
|
|
|
V. A. Kiri, N. B. Pride, J. B. Soriano, and J. Vestbo Inhaled Corticosteroids in Chronic Obstructive Pulmonary Disease: Results from Two Observational Designs Free of Immortal Time Bias Am. J. Respir. Crit. Care Med., August 15, 2005; 172(4): 460 - 464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Barber "Chronic obstructive pulmonary disease": the diagnostic last refuge of the intellectually challenged? Eur. Respir. J., October 1, 2004; 24(4): 710 - 711. [Full Text] [PDF]
|
|
|
|
|
|
S. Suissa From the Author Eur. Respir. J., July 1, 2004; 24(1): 191 - 192. [Full Text] [PDF]
|
|
|
|
|
|
V.A. Kiri, J. Vestbo, N.B. Pride, and J.B. Soriano Inhaled steroids and mortality in COPD: bias from unaccounted immortal time. Eur. Respir. J., July 1, 2004; 24(1): 190 - 191. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |