Comparative effectiveness of combination therapies in COPD

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Effectiveness study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (R03AC) Selective beta-2-adrenoreceptor agonists

  Selective beta-2-adrenoreceptor agonists

  (R03BA) Glucocorticoids

  Glucocorticoids

  (R03BB) Anticholinergics

  Anticholinergics
• Medical condition to be studied:
  Chronic obstructive pulmonary disease

Population studied

• Short description of the study population:
  Patients with COPD aged 55 years or older who were new users of tiotropium, LABA or ICS between 1 January 2002 and 31 December 2015.
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Special population of interest:
  Other
• Special population of interest, other:
  Chronic obstructive pulmonary disease (COPD) patients
• Estimated number of subjects:
  6000

Study design details

• Main study objective:
  To assess the effectiveness of maintenance treatment of COPD with the combination of a LABA and the LAMA tiotropium (LABA-TIO) compared with the combination of a LABA and an ICS (LABA-ICS) on the time to COPD exacerbation.
• Outcomes:
  The primary outcome event is the first COPD exacerbation to occur after cohort entry. The event is defined as a hospitalization for COPD (severe exacerbation) or the prescription of an oral corticosteroid, namely prednisolone (moderate exacerbation). The first secondary outcome is the rate of COPD exacerbations over the one-year follow-up. This outcome will be based on the number of hospitalizations and on the number of courses of treatment with an oral corticosteroid. A gap of at least 30 days between treatment courses will be required to consider the exacerbations as separate
• Data analysis plan:
  For the analysis of the primary objective, the matched cohort will be used to estimate the crude 1-year cumulative incidence of severe and moderate COPD exacerbations for the two combination treatment groups. The main comparative analysis will also be based on the matched cohort and a time-dependent Cox proportional hazard regression model to perform an as-treated analysis that assesses the effect of current use of LABA-TIO combination versus the LABA-ICS combination on the risk of a first COPD exacerbation. It will provide an estimate of the hazard ratio (HR) of a COPD exacerbation associated with LABA-TIO use relative to LABA-ICS use, along with 95% confidence intervals (CI). Current use will be defined as a prescription dispensed within the 60-day period of the date defined by the risk set of the Cox model. This approach allows consideration of exposure as time-dependent, accounting for the changes in exposure during the follow-up.