Performance of the EXAcerbations of Chronic Pulmonary Disease Tool Patient-reported Outcome Measure in Three Clinical Trials of Chronic Obstructive Pulmonary Disease

RATIONALE: 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. OBJECTIVES: 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. MEASUREMENTS AND MAIN 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).