title: Performance of the EXAcerbations of chronic pulmonary disease tool patient-reported outcome measure in three clinical trials of chronic obstructive pulmonary disease.
abstract: BACKGROUND
  The EXAcerbations of Chronic Pulmonary Disease Tool (EXACT) is a patient-reported outcome measure to standardize the symptomatic assessment of chronic obstructive pulmonary disease exacerbations, including reported and unreported events. The instrument has been validated in a short-term study of patients with acute exacerbation and stable disease; its performance in longer-term studies has not been assessed.
  
  
  OBJECTIVE
  To test the EXACT's performance in three randomized controlled trials and describe the relationship between resource-defined medically treated exacerbations (MTEs) and symptom (EXACT)-defined events.
  
  
  METHODS
  Prespecified secondary analyses of data from phase II randomized controlled trials testing new drugs for the management of chronic obstructive pulmonary disease: one 6-month trial (United States) (n = 235) and two 3-month, multinational trials (AZ 1 [n = 749], AZ 2 [n = 597]). In each case, the experimental drugs were found to be ineffective, permitting assessment of the EXACT's performance in three independent studies of moderate to severe high-risk patients on maintenance therapies.
  
  
  RESULTS
  The mean age of subjects was 62 to 64 years; 48 to 76% were male. Mean FEV1 % predicted was 42 to 59%. EXACT scores exhibited internal consistency (Cronbach's α ≥ 0.90), reproducibility (intraclass correlation ≥ 0.70), correlation with St. George's Respiratory Questionnaire (Spearman rho [rs] = 0.62, 0.46, 0.46 in the three trials; P < 0.001), and Breathlessness Cough and Sputum Scale (AZ 1, rs = 0.83; AZ 2, rs = 0.83; P < 0.001). EXACT-defined events had a high correspondence with alternative indicators of worsening (94, 88, and 93%). In each trial, unreported events were similar in severity (mean EXACT score, 56, 57, 61 vs. 53, 54 [P < 0.05], 57 [P < 0.05], respectively; 100-point scale) and longer (median, 9, 8, 7 vs. 8, 7 [P < 0.01], 6 days, respectively) than moderate MTEs.
  
  
  CONCLUSIONS
  Data generated through the EXACT offers insight into the symptomatic nature of MTEs and the frequency, severity, and duration of unreported symptom-defined events. Clinical trials registered with www.clinicaltrials.gov (MPEX: NCT00739648; AZ 1: NCT00949975; AZ 2: NCT01023516).
authors.affiliation: 1 Evidera, Bethesda, Maryland.
authors.forename: Nancy K
authors.initials: NK
authors.lastname: Leidy
authors.forename: Lindsey T
authors.initials: LT
authors.lastname: Murray
authors.forename: Paul
authors.initials: P
authors.lastname: Jones
authors.forename: Sanjay
authors.initials: S
authors.lastname: Sethi
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001993:Bronchodilator Agents / Q000627:therapeutic use; D015331:Cohort Studies; D005260:Female; D006801:Humans; D064704:Levofloxacin / Q000627:therapeutic use; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000188:drug therapy*; D011728:Pyridones / Q000627:therapeutic use; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D013450:Sulfones / Q000627:therapeutic use; D011795:Surveys and Questionnaires; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D001993:Bronchodilator Agents; D011728:Pyridones; D013450:Sulfones; D064704:Levofloxacin; C568080:N-((5-(methanesulfonyl)pyridin-2-yl)methyl)-6-methyl-5-(1-methyl-1H-pyrazol-5-yl)-2-oxo-1-(3-(trifluoromethyl)phenyl)-1,2-dihydropyridine-3-carboxamide