Vol 79, No 3 (2011)
Review paper
Published online: 2011-04-21
Submitted: 2013-02-22
Mega trials in COPD - clinical data analysis and design issues
Samy Suissa, Pierre Ernst
Pneumonol Alergol Pol 2011;79(3):227-231.
Vol 79, No 3 (2011)
EDUKACJA. Zmniejszmy ciężar przewlekłej obturacyjnej choroby płuc (cz. II)
Published online: 2011-04-21
Submitted: 2013-02-22
Abstract
The TORCH and UPLIFT randomised controlled trials have provided important data on the benefits of COPD treatments, but
also some lessons in study design and data analysis that we will here review.
Firstly, it is fundamental that the study question be answerable by the study design. The question in the TORCH study was
aimed at a comparison with ‘usual care’, but the placebo group was not ‘usual care’. Secondly, TORCH and UPLIFT were
among the first trials to follow the intent-to-treat principle, fundamental to avoid bias in randomised trials. However, this
principle was followed for the mortality outcome, but not for lung function, so that the findings related to lung function
decline are subject to bias from regression to the mean. Finally, a re-analysis of the TORCH study (performed to fully exploit
the data as a 2 × 2 factorial trial) shows that a mortality benefit is entirely accounted for by the effect of the long-acting
beta-agonist salmeterol, with no effect attributable to the inhaled corticosteroid fluticasone component of the combination
therapy. Together, these data suggest that long-acting bronchodilators, including anticholinergics such as tiotropium and
beta-agonists, are associated with lower mortality of patients with COPD, but not inhaled corticosteroids. With COPD one of
the major causes of morbidity and mortality worldwide, mega trials such as TORCH and UPLIFT are much needed, but must
achieve the utmost scientific rigour in their design and analysis.
Pneumonol. Alergol. Pol. 2011; 79, 3: 227-231
Abstract
The TORCH and UPLIFT randomised controlled trials have provided important data on the benefits of COPD treatments, but
also some lessons in study design and data analysis that we will here review.
Firstly, it is fundamental that the study question be answerable by the study design. The question in the TORCH study was
aimed at a comparison with ‘usual care’, but the placebo group was not ‘usual care’. Secondly, TORCH and UPLIFT were
among the first trials to follow the intent-to-treat principle, fundamental to avoid bias in randomised trials. However, this
principle was followed for the mortality outcome, but not for lung function, so that the findings related to lung function
decline are subject to bias from regression to the mean. Finally, a re-analysis of the TORCH study (performed to fully exploit
the data as a 2 × 2 factorial trial) shows that a mortality benefit is entirely accounted for by the effect of the long-acting
beta-agonist salmeterol, with no effect attributable to the inhaled corticosteroid fluticasone component of the combination
therapy. Together, these data suggest that long-acting bronchodilators, including anticholinergics such as tiotropium and
beta-agonists, are associated with lower mortality of patients with COPD, but not inhaled corticosteroids. With COPD one of
the major causes of morbidity and mortality worldwide, mega trials such as TORCH and UPLIFT are much needed, but must
achieve the utmost scientific rigour in their design and analysis.
Pneumonol. Alergol. Pol. 2011; 79, 3: 227-231
Keywords
drug effectiveness; methods; chronic obstructive pulmonary disease; inhaled corticosteroids; anticholinergics; long-acting beta-agonist
Title
Mega trials in COPD - clinical data analysis and design issues
Journal
Advances in Respiratory Medicine
Issue
Vol 79, No 3 (2011)
Article type
Review paper
Pages
227-231
Published online
2011-04-21
Bibliographic record
Pneumonol Alergol Pol 2011;79(3):227-231.
Keywords
drug effectiveness
methods
chronic obstructive pulmonary disease
inhaled corticosteroids
anticholinergics
long-acting beta-agonist
Authors
Samy Suissa
Pierre Ernst