Eric D Bateman1, Dirk Esser2, Costel Chirila3, Maria Fernandez3, Andy Fowler4, Petra Moroni-Zentgraf5, J Mark FitzGerald6. 1. Department of Medicine, University of Cape Town, Cape Town, South Africa. Electronic address: Eric.Bateman@uct.ac.za. 2. Global Health Economics and Outcomes Research, Boehringer Ingelheim GmbH, Ingelheim am Rhein, Germany. 3. RTI Health Solutions, Research Triangle Park, NC. 4. Clinical Research, Boehringer Ingelheim Ltd, Bracknell, United Kingdom. 5. TA Respiratory Diseases, Boehringer Ingelheim GmbH, Ingelheim am Rhein, Germany. 6. Lung Centre, Gordon and Leslie Diamond Health Care Centre, Vancouver, British Columbia, Canada.
Abstract
BACKGROUND: The Asthma Quality of Life Questionnaire (AQLQ) and the Asthma Control Questionnaire (ACQ) are widely used in asthma research; however, in studies of newer asthma treatments, mean improvements in these measures compared with placebo arms do not exceed the minimal important difference (MID), particularly when a new treatment is added to current treatment. OBJECTIVE: We performed a systematic review and network meta-analysis to examine the magnitude of AQLQ and ACQ responses achieved with commonly used asthma drugs and factors influencing these end points in clinical trials. METHODS: A systematic literature search was conducted to identify blinded randomized controlled trials reporting AQLQ or ACQ results. Mixed treatment comparisons, combined with meta-regression, were then performed. RESULTS: Of the 64 randomized controlled trials (42,527 patients) identified, 54 included the AQLQ and 11 included the ACQ as end points. The presence of a run-in period, the nature of treatment during the run-in period, concurrent treatment during the treatment period, and instrument version significantly influenced the change in AQLQ score from baseline and whether it exceeded the MID. When compared with placebo, only inhaled corticosteroids (ICSs), with or without a long-acting β-agonist, achieved the MID. The ACQ results were comparable with those of the AQLQ: no differences from placebo exceeded the MID, and ICS-based treatments provided the greatest improvements. CONCLUSION: The established within-patient MID for the ACQ and AQLQ is not achievable as a group-wise efficacy threshold between treatment arms in clinical studies in which controllers are added to ICS treatment. Thus in addition to reporting mean changes of the instruments, other measurement criteria should be considered, including responder analyses.
BACKGROUND: The Asthma Quality of Life Questionnaire (AQLQ) and the Asthma Control Questionnaire (ACQ) are widely used in asthma research; however, in studies of newer asthma treatments, mean improvements in these measures compared with placebo arms do not exceed the minimal important difference (MID), particularly when a new treatment is added to current treatment. OBJECTIVE: We performed a systematic review and network meta-analysis to examine the magnitude of AQLQ and ACQ responses achieved with commonly used asthma drugs and factors influencing these end points in clinical trials. METHODS: A systematic literature search was conducted to identify blinded randomized controlled trials reporting AQLQ or ACQ results. Mixed treatment comparisons, combined with meta-regression, were then performed. RESULTS: Of the 64 randomized controlled trials (42,527 patients) identified, 54 included the AQLQ and 11 included the ACQ as end points. The presence of a run-in period, the nature of treatment during the run-in period, concurrent treatment during the treatment period, and instrument version significantly influenced the change in AQLQ score from baseline and whether it exceeded the MID. When compared with placebo, only inhaled corticosteroids (ICSs), with or without a long-acting β-agonist, achieved the MID. The ACQ results were comparable with those of the AQLQ: no differences from placebo exceeded the MID, and ICS-based treatments provided the greatest improvements. CONCLUSION: The established within-patient MID for the ACQ and AQLQ is not achievable as a group-wise efficacy threshold between treatment arms in clinical studies in which controllers are added to ICS treatment. Thus in addition to reporting mean changes of the instruments, other measurement criteria should be considered, including responder analyses.
Authors: Diana M Sobieraj; Erin R Weeda; Elaine Nguyen; Craig I Coleman; C Michael White; Stephen C Lazarus; Kathryn V Blake; Jason E Lang; William L Baker Journal: JAMA Date: 2018-04-10 Impact factor: 56.272
Authors: Diana M Sobieraj; William L Baker; Elaine Nguyen; Erin R Weeda; Craig I Coleman; C Michael White; Stephen C Lazarus; Kathryn V Blake; Jason E Lang Journal: JAMA Date: 2018-04-10 Impact factor: 56.272
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Authors: Anne Bruton; Amanda Lee; Lucy Yardley; James Raftery; Emily Arden-Close; Sarah Kirby; Shihua Zhu; Manimekalai Thiruvothiyur; Frances Webley; Lyn Taylor; Denise Gibson; Guiqing Yao; Mark Stafford-Watson; Jenny Versnel; Michael Moore; Steve George; Paul Little; Ratko Djukanovic; David Price; Ian D Pavord; Stephen T Holgate; Mike Thomas Journal: Lancet Respir Med Date: 2017-12-14 Impact factor: 30.700