Long-term health-related quality-of-life and symptom response profiles with arformoterol in COPD: results from a 52-week trial

James F Donohue,1 Vamsi K Bollu,2 Donald E Stull,3 Lauren M Nelson,4 Valerie SL Williams,4 Michael D Stensland,5 Nicola A Hanania6 1Department of Pulmonary Diseases and Critical Care Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 2Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, NJ, 3Data Analytics and Design Strategy, 4Psychometrics, RTI Health Solutions, Research Triangle Park, NC, 5Agile Outcomes Research, Inc., Rochester, MN, 6Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX, USA Background: Symptom severity is the largest factor in determining subjective health in COPD. Symptoms (eg, chronic cough, dyspnea) are associated with decreased health-related quality of life (HRQoL). We evaluated the impact of arformoterol on HRQoL in COPD patients, measured by St George’s Respiratory Questionnaire (SGRQ). Post hoc growth mixture model (GMM) analysis examined symptom response profiles. Methods: We examined data from a randomized, double-blind, parallel-group, 12-month safety trial of twice-daily nebulized arformoterol 15 µg (n=420) versus placebo (n=421). COPD severity was assessed by Global Initiative for Chronic Obstructive Lung Disease (GOLD) status. GMM analysis identified previously unknown patient subgroups and examined the heterogeneity in response to SGRQ Symptoms scores. Results: SGRQ Total score improved by 4.24 points with arformoterol and 2.02 points with placebo (P=0.006). Significantly greater improvements occurred for arformoterol versus placebo in SGRQ Symptoms (6.34 vs 4.25, P=0.031) and Impacts (3.91 vs 0.97, P=0.001) scores, but not in Activity score (3.57 vs 1.75, P=0.057). GMM identified responders and nonresponders based on the SGRQ Symptoms score. End-of-study mean difference in SGRQ Symptoms scores between these latent classes was 20.7 points (P<0.001; 95% confidence interval: 17.6–23.9). Compared with nonresponders, responders were more likely current smokers (55.52% vs 44.02%, P=0.0021) and had more severe COPD (forced expiratory volume in 1 second [FEV1]: 1.16 vs 1.23 L, P=0.0419), more exacerbations (0.96 vs 0.69, P=0.0018), and worse mean SGRQ Total (59.81 vs 40.57, P<0.0001), Clinical COPD Questionnaire (3.29 vs 2.05, P<0.0001), and Modified Medical Research Council Dyspnea Scale (3.13 vs 2.75, P<0.0001) scores. Arformoterol-receiving responders exhibited significantly greater improvements in FEV1 (0.09 vs 0.008, P=0.03) and fewer hospitalizations (0.13 vs 0.24, P=0.02) than those receiving placebo. Conclusion: In this study, arformoterol treatment significantly improved HRQoL reflected by SGRQ. For the analysis performed on these data, arformoterol may be particularly effective in improving lung function and reducing hospitalizations among patients who are unable to quit smoking or present with more severe symptoms. Keywords: St George’s Respiratory Questionnaire, growth mixture model, HRQoL, long-acting beta agonis

Construction of the Pediatric Asthma Impact Scale (PAIS) for the Patient-Reported Outcomes Measurement Information System (PROMIS)

BACKGROUND: Recently, the National Institutes of Health Roadmap for Medical Research initiative led a large-scale effort to develop the Patient-Reported Outcomes Measurement Information System (PROMIS). PROMIS’s main goal was to develop a set of item banks and computerized adaptive tests for the clinical research community. Asthma, as the most common chronic childhood disease, was chosen for a disease-specific pediatric item bank. OBJECTIVES: The primary objective of this research is to present the details of the psychometric analyses of the asthma domain items. METHODS: Item response theory (IRT) analyses were conducted on a 34–asthma item bank. Test forms containing PROMIS Pediatric Asthma domain items were completed by 622 children ages 8 to 12. Items were subsequently evaluated for local dependence, scale dimensionality, and differential item functioning. RESULTS: A 17-item pool and an 8-item short form for the new PROMIS Pediatric Asthma Impact Scale (PAIS) were generated using IRT. The recommended 8-item short form contains the item set that provides the maximum test information at the mean (50) on the T-score metric. If more score precision is required, the complete 17-item pool is recommended and may be used in toto or as the basis of a computerized adaptive test (CAT). A shorter test form can also be created and scored on the same scale. CONCLUSIONS: The present study presents the PROMIS Pediatric Asthma Impact Scale (PAIS) developed with IRT, and provides the initial calibration data for the items