[Methodological controversies in chronic obstructive pulmonary disease therapeutic trials]

Area of Science:

• Pulmonology
• Pharmacology
• Clinical Trials

Context:

• Pharmacological treatment for chronic obstructive pulmonary disease (COPD) primarily uses long-acting bronchodilators.
• Inhaled corticosteroids (ICS) were introduced for COPD without initial randomized trials, leading to decades of controversial efficacy data.
• Numerous studies and meta-analyses on ICS for COPD have yielded contradictory and debated results.

Purpose:

• To critically evaluate the evidence supporting the use of inhaled corticosteroids (ICS) in the management of chronic obstructive pulmonary disease (COPD).
• To identify methodological flaws in randomized trials and observational studies that may create a false appearance of ICS efficacy.
• To assess the risks associated with ICS, including ocular damage and pneumonia, particularly in elderly patients.

Summary:

• Randomized trials for ICS in COPD often violate intention-to-treat principles and introduce bias through treatment interruption or run-in periods.
• Observational studies reporting significant mortality reductions with ICS are distorted by biases such as "immortal time" bias.
• Recent findings suggest that the benefits of ICS/bronchodilator combinations may primarily stem from the bronchodilator component.

Impact:

• The lack of proven efficacy and associated risks (ocular damage, pneumonia) make ICS difficult to recommend for general COPD treatment.
• Current high-dose ICS prescriptions in COPD are questioned given the evidence.
• ICS should be reserved for a very limited patient population within COPD management.