Measuring respiratory symptoms of COPD: performance of the EXACT- Respiratory Symptoms Tool (E-RS) in three clinical trials

Respiratory Research

Sanjay Sethi¹  Elizabeth J Dansie⁵  Paul W Jones⁴  Mitchell Goldman⁶  Linda Nelsen²  Brigitta U Monz³  Lindsey T Murray⁵  Nancy K Leidy⁵ 

[1] University of Buffalo, Buffalo, NY, USA;Merck, Sharp & Dohme, Corp, Whitehouse Station, NJ, USA;Formerly Boehringer Ingelheim GmbH, Ingelheim, Germany;St. George’s, University of London, London, UK;Evidera, 7101 Wisconsin Ave, Suite 1400, Bethesda 20814, MD, USA;AstraZeneca, Wilmington, DE, USA

关键词: Chest symptoms;    Sputum;    Cough;    Dyspnoea;    Clinical trials;    Respiratory symptoms;    COPD;   

Others  :  1137259
DOI  :  10.1186/s12931-014-0124-z

 received in 2014-07-23, accepted in 2014-09-30,  发布年份 2014

【 摘 要 】

Background

Symptomatic relief is an important treatment goal for patients with COPD. To date, no diary for evaluating respiratory symptoms in clinical trials has been developed and scientifically-validated according to FDA and EMA guidelines. The EXACT – Respiratory Symptoms (E-RS) scale is a patient-reported outcome (PRO) measure designed to address this need. The E-RS utilizes 11 respiratory symptom items from the existing and validated 14-item EXACT, which measures symptoms of exacerbation. The E-RS total score quantifies respiratory symptom severity, and 3 domains assess breathlessness, cough and sputum, and chest symptoms.

Methods

This study examined the performance of the E-RS in each of 3 controlled trials with common and unique validation variables: one 6-month (N = 235, US) and two 3-month (N = 749; N = 597; international). Subjects completed the E-RS as part of a daily eDiary. Tests of reliability, validity, and responsiveness were conducted in each dataset.

Results

In each study, RS-Total score was internally consistent (Cronbach α) (0.88, 0.92, 0.92) and reproducible (intra-class correlation) in stable patients (2 days apart: 0.91; 7 days apart: 0.71, 0.74). RS-Total scores correlated significantly with the following criterion variables (Spearman’s rho; p < 0.01, all comparisons listed here): FEV₁% predicted (−0.19, −0.14, −0.15); St. George’s Respiratory Questionnaire (SGRQ) (0.65, 0.52, 0.51); Breathlessness, Cough, and Sputum Scale (BCSS) (0.89, 0.89); modified Medical Research Council dyspnoea scale (mMRC) (0.40); rescue medication use (0.43, 0.42); Functional Performance Inventory Short-Form (FPI-SF) (0.43); 6-minute walk distance (6-MWT) (−0.30, −0.14) and incremental shuttle walk (ISWT) (−0.18) tests. Correlations between these variables and RS-Breathlessness, RS-Cough and Sputum, RS-Chest Symptoms scores supported subscale validity. RS-Total, RS-Breathlessness, and RS-Chest Symptoms differentiated mMRC levels of breathlessness severity (p < 0.0001). RS-Total and domain scores differentiated subjects with no rescue medication use and 3 or more puffs (p < 0.0001). Sensitivity to changes in health status (SGRQ), symptoms (BCSS), and exercise capacity (6MWT, ISWT) were also shown and responder definitions using criterion- and distribution-based methods are proposed.

Conclusions

Results suggest the E-RS is a reliable, valid, and responsive measure of respiratory symptoms of COPD suitable for use in natural history studies and clinical trials.

Trial registration

MPEX: NCT00739648 webcite; AZ1: NCT00949975 webcite; AZ 2: NCT01023516 webcite

【 授权许可】

   
2014 Leidy et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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