title: [Methodological controversies in chronic obstructive pulmonary disease therapeutic trials].
abstract: Pharmacological treatment of chronic obstructive pulmonary disease (COPD) relies principally on long-acting bronchodilators. Inhaled corticosteroids (ICS) were introduced for COPD two decades ago, despite the fact that no randomized trial had yet assessed their efficacy for this indication. Since then, the numerous randomized trials and meta-analyses performed to justify their use in COPD have been contradictory and controversial. Moreover, observational studies have reported efficacy rates so exceptional that they are almost too good to be true. These studies contain important methodological flaws that produce the appearance of efficacy. The randomized trials infringe the fundamental principle of intention-to-treat analysis, an analysis necessary to prevent important biases. Two other complications are the interruption of treatment at the moment of randomization and the use of a run-in period; in both cases, the withdrawal of treatment can introduce bias. The observational studies reporting phenomenal reductions in mortality with ICS were distorted by "immortal time" bias. Finally, recent data suggest that the effect of ICS/bronchodilator combinations is due mainly to the effect of the long-acting bronchodilator. Given the absence of proof of the efficacy of inhaled corticosteroids in COPD and their associated risks, especially of ocular damage and pneumonia, and particularly among the elderly, as well as the high doses currently prescribed in COPD, it is difficult to recommend their use in this indication. They should be prescribed in COPD for at most a limited population of patients.
authors.affiliation: Hôpital Général Juif de Montréal et Départements d'Epidémiologie et Biostatistique, et de Médecine, Université McGill, Montréal, Canada. samy.suissa@mcgill.ca
authors.forename: Samy
authors.initials: S
authors.lastname: Suissa
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use*; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000592:standards; D006801:Humans; D015201:Meta-Analysis as Topic; D015588:Observer Variation; D018579:Patient Selection; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic / Q000592:standards; D015203:Reproducibility of Results
chemical_list: D000305:Adrenal Cortex Hormones; D001993:Bronchodilator Agents