Clare Saunders1, Renee Jensen2, Paul D Robinson3, Sanja Stanojevic4, Michelle Klingel5, Christopher Short1, Jane C Davies1, Felix Ratjen6. 1. Royal Brompton & Harefield NHS Foundation Trust, London, United Kingdom; National Heart and Lung Institute, Imperial College London, United Kingdom. 2. Translational Medicine, Hospital for Sick Children, Toronto, Canada. Electronic address: renee.jensen@sickkids.ca. 3. Department of Respiratory Medicine, The Children's Hospital at Westmead, Sydney, New South Wales, Australia; Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, Australia. 4. Translational Medicine, Hospital for Sick Children, Toronto, Canada; University of Toronto, Toronto, Canada. 5. Translational Medicine, Hospital for Sick Children, Toronto, Canada. 6. Translational Medicine, Hospital for Sick Children, Toronto, Canada; University of Toronto, Toronto, Canada. Electronic address: felix.ratjen@sickkids.ca.
Abstract
BACKGROUND: The lung clearance index (LCI), derived from the Multiple Breath Washout (MBW) test, is sensitive to treatment effects and compared with spirometry has higher feasibility in younger children and requires smaller sample sizes. As a result, the LCI has been endorsed by the European CF Society Clinical Trials Network for use as a primary outcome measure in CF clinical trials. METHODS: Here we describe the implementation of standardised protocols for MBW test performance, data collection and quality control to successfully incorporate LCI as a novel outcome measure in a large multicentre phase III clinical trial. RESULTS: Three regional (North America (NA), Europe (EU), Australia (AUS)) central over-reading centres (CORC) were established to provide a collaborative platform for MBW training, certification and quality control of data. One hundred and thirty-two naïve operators from 53 sites across NA, EU and AUS were successfully trained and certified to perform MBW testing. Incorporation of a re-screening opportunity in the study protocol resulted a final screening feasibility rate of 93%, success remained high throughout the study resulting in an overall feasibility of MBW study data of 88.1% (1107/1257). MBW test acceptability was similar between geographical regions: NA (88%), EU (89%) and AUS (89%). CONCLUSION: With this approach we achieved high MBW test feasibility and sustained collection of good quality data, demonstrating the utility of LCI as an effective primary endpoint in the first international phase III clinical trial to report LCI as the primary outcome.
BACKGROUND: The lung clearance index (LCI), derived from the Multiple Breath Washout (MBW) test, is sensitive to treatment effects and compared with spirometry has higher feasibility in younger children and requires smaller sample sizes. As a result, the LCI has been endorsed by the European CF Society Clinical Trials Network for use as a primary outcome measure in CF clinical trials. METHODS: Here we describe the implementation of standardised protocols for MBW test performance, data collection and quality control to successfully incorporate LCI as a novel outcome measure in a large multicentre phase III clinical trial. RESULTS: Three regional (North America (NA), Europe (EU), Australia (AUS)) central over-reading centres (CORC) were established to provide a collaborative platform for MBW training, certification and quality control of data. One hundred and thirty-two naïve operators from 53 sites across NA, EU and AUS were successfully trained and certified to perform MBW testing. Incorporation of a re-screening opportunity in the study protocol resulted a final screening feasibility rate of 93%, success remained high throughout the study resulting in an overall feasibility of MBW study data of 88.1% (1107/1257). MBW test acceptability was similar between geographical regions: NA (88%), EU (89%) and AUS (89%). CONCLUSION: With this approach we achieved high MBW test feasibility and sustained collection of good quality data, demonstrating the utility of LCI as an effective primary endpoint in the first international phase III clinical trial to report LCI as the primary outcome.
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Authors: Katherine O'Neill; Kathryn Ferguson; Denis Cosgrove; Michael M Tunney; Anthony De Soyza; Mary Carroll; James D Chalmers; Timothy Gatheral; Adam T Hill; John R Hurst; Christopher Johnson; Michael R Loebinger; Gerhild Angyalosi; Charles S Haworth; Renee Jensen; Felix Ratjen; Clare Saunders; Christopher Short; Jane C Davies; J Stuart Elborn; Judy M Bradley Journal: ERJ Open Res Date: 2020-10-13
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