title: Comorbidities of patients in tiotropium clinical trials: comparison with observational studies of patients with chronic obstructive pulmonary disease.
abstract: BACKGROUND
  There is an ongoing debate on whether patients with chronic obstructive pulmonary disease (COPD) seen in real-life clinical settings are represented in randomized controlled trials (RCTs) of COPD. It is thought that the stringent inclusion and exclusion criteria of RCTs may prevent the participation of patients with specific characteristics or risk factors.
  
  
  METHODS
  We surveyed a database of patients recruited into 35 placebo-controlled tiotropium RCTs and also conducted a systematic literature review of large-scale observational studies conducted in patients with a documented diagnosis of COPD between 1990 and 2013. Patient demographics and comorbidities with a high prevalence in patients with COPD were compared between the two patient populations at baseline. Using the Medical Dictionary for Regulatory Activities (MedDRA; v 14.0), patient comorbidities in the pooled tiotropium RCTs were classified according to system organ class, pharmacovigilance (PV) endpoints, and Standardised MedDRA Queries to enable comparison with the observational studies.
  
  
  RESULTS
  We identified 24,555 patients in the pooled tiotropium RCTs and 61,361 patients among the 13 observational studies that met our search criteria. The Global initiative for chronic Obstructive Lung Disease (GOLD) staging of patients in the RCTs differed from that in observational studies: the proportion of patients with GOLD stages I+II disease ranged from 40.0% to 51.5% in the RCTs but 24.5% to 44.1% in the observational studies; for GOLD stage III or IV disease these ranges were 7.2%-45.8% (RCTs) and 13.7-42.1% (observational studies). The comorbidities with the highest prevalence reported in the RCTs and observational studies were: hypertension (39.4%-40.0% vs 40.1%-60.6%), other ischemic heart disease (12.3%-14.2% vs 12.5%-41.0%), diabetes (10.3%-10.9% vs 4.0%-38.9%), depression (8.5%-9.5% vs 17.0%-20.6%), and cardiac arrhythmia (7.8%-11.4% vs 11.3%-15.8%).
  
  
  CONCLUSIONS
  The clinical profile of COPD patients treated in the tiotropium trial program appears to be largely in the range of clinical characteristics, including cardiovascular comorbidities, reported for "real-life patients." The tiotropium RCTs tended to include patients with more severe disease than the observational studies.
authors.affiliation: Pneumology Department, Hospital Universitari Vall d'Hebron, Ciber de Enfermedades Respiratorias (CIBERES), Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Miravitlles
authors.affiliation: Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: David
authors.initials: D
authors.lastname: Price
authors.affiliation: Department of Medicine, Christian-Albrechts-Universität zu Kiel (CAU), Großhansdorf, Germany ; LungenClinic Grosshansdorf, Großhansdorf, Germany.
authors.forename: Klaus F
authors.initials: KF
authors.lastname: Rabe
authors.affiliation: Global Biometrics and Clinical Applications, Boehringer Ingelheim Pharma GmbH and Co KG, Ingelheim am Rhein, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Schmidt
authors.affiliation: TA Respiratory Diseases, Boehringer Ingelheim Pharma GmbH and Co KG, Ingelheim am Rhein, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Metzdorf
authors.affiliation: Pulmonary Division, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Bartolome
authors.initials: B
authors.lastname: Celli
mesh_terms: D000368:Aged; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000453:epidemiology*; D018680:Cholinergic Antagonists / Q000627:therapeutic use*; D015897:Comorbidity; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D064887:Observational Studies as Topic; D015995:Prevalence; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D000069447:Tiotropium Bromide / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D000069447:Tiotropium Bromide
keywords: GOLD staging; baseline characteristics; epidemiology; patient population; real-life patients
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