Predictors of treatment REsponse to inhaled corticosteroids (ICS) in Chronic Obstructive pulmonary disease: randomised controlled trials individual participant Data re-Evaluation–protocol of the ICS-RECODE individual participant data meta-analysis
Introduction Inhaled corticosteroids (ICS) can improve clinical outcomes in patients with chronic obstructive pulmonary disease (COPD) and eosinophilic airway inflammation, but they also increase the risk of side effects like pneumonia. Blood eosinophils guide ICS use, though evidence is limited. Th...
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2025-03-01
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| author | Matthew Sperrin John R Hurst Michael Miligkos Joergen Vestbo Pradeesh Sivapalan Mike Clarke Lesley Stewart Jørgen Vestbo Dave Singh Tim Felton Alexander G Mathioudakis Rebecca Fortescue Jennifer Quint Jonathan Marshall Anurita Majumdar Jan Hansel Alice M Turner Sinduja Manohar Catherine Fullwood Nawar Diar Bakerly Mark Simmonds Steven Barnes Ashley Woodcock Sebastian Bate Jens-Ulrik Jensen Markus Fally Helen Ashdown Ashley A Woodcock Emily Howlett John Linnell Alan Preston Glauco Cappellini Dmitry Galkin Olaf Joens |
| author_facet | Matthew Sperrin John R Hurst Michael Miligkos Joergen Vestbo Pradeesh Sivapalan Mike Clarke Lesley Stewart Jørgen Vestbo Dave Singh Tim Felton Alexander G Mathioudakis Rebecca Fortescue Jennifer Quint Jonathan Marshall Anurita Majumdar Jan Hansel Alice M Turner Sinduja Manohar Catherine Fullwood Nawar Diar Bakerly Mark Simmonds Steven Barnes Ashley Woodcock Sebastian Bate Jens-Ulrik Jensen Markus Fally Helen Ashdown Ashley A Woodcock Emily Howlett John Linnell Alan Preston Glauco Cappellini Dmitry Galkin Olaf Joens |
| collection | DOAJ |
| description | Introduction Inhaled corticosteroids (ICS) can improve clinical outcomes in patients with chronic obstructive pulmonary disease (COPD) and eosinophilic airway inflammation, but they also increase the risk of side effects like pneumonia. Blood eosinophils guide ICS use, though evidence is limited. The predictors of treatment REsponse to ICS in COPD: a randomised controlled trials (RCTs) individual participant Data re-Evaluation (ICS-RECODE) research programme will leverage data from large RCTs to identify patients who benefit most from ICS with minimal risk. This protocol details an individual participant data (IPD) meta-analysis, assessing ICS safety, efficacy and treatment×covariate interactions to identify predictors of treatment response.Methods and analysis This meta-analysis will adhere to Cochrane, IPD handbook and Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance. We will conduct a two-stage IPD meta-analysis of RCTs evaluating the addition of ICS to maintenance COPD treatments. Only RCTs with at least 500 participants across all eligible arms will be included, to allow for treatment×covariate interaction evaluation. Primary outcomes are severe and moderate or severe exacerbation rates; secondary outcomes assess both safety and efficacy. Data from each RCT will be reanalysed using rigorous, consistent statistical methods. Treatment×covariate interactions will be assessed at the RCT level. Trial treatment effects and the coefficients of treatment×covariate interaction analyses will be pooled using random effects model meta-analysis. Risk of bias will be appraised using RoB-2 informed by IPD, and certainty of evidence will be assessed with GRADE and the Instrument to assess the Credibility of Effect Modification Analyses.The ICS-RECODE IPD meta-analysis will make use of the best available data to define evidence-based, precision medicine approaches for ICS use in COPD.Ethics and dissemination The Health Research Authority approved the ICS-RECODE study, exempting it from ethics review (HRA UK, Reference: 24/HRA/0460). Our findings will be published in peer-reviewed journals and shared with the scientific and broader stakeholder communities.PROSPERO registration number CRD42024508286. |
| format | Article |
| id | doaj-art-fea239c582ac458080c6415ced884e41 |
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| issn | 2044-6055 |
| language | English |
| publishDate | 2025-03-01 |
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| spelling | doaj-art-fea239c582ac458080c6415ced884e412025-08-20T03:16:22ZengBMJ Publishing GroupBMJ Open2044-60552025-03-0115310.1136/bmjopen-2024-095541Predictors of treatment REsponse to inhaled corticosteroids (ICS) in Chronic Obstructive pulmonary disease: randomised controlled trials individual participant Data re-Evaluation–protocol of the ICS-RECODE individual participant data meta-analysis Matthew Sperrin0John R Hurst1Michael Miligkos2Joergen Vestbo3Pradeesh Sivapalan4Mike ClarkeLesley Stewart5Jørgen VestboDave Singh6Tim FeltonAlexander G Mathioudakis7Rebecca Fortescue8Jennifer QuintJonathan MarshallAnurita MajumdarJan Hansel9Alice M TurnerSinduja Manohar10Catherine Fullwood11Nawar Diar BakerlyMark Simmonds12Steven BarnesAshley WoodcockSebastian Bate13Jens-Ulrik JensenMarkus Fally14Helen AshdownAshley A Woodcock15Emily Howlett16John Linnell17Alan Preston18Glauco CappelliniDmitry GalkinOlaf Joens4 Centre for Health Informatics, Imaging and Data Science, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UKUCL Respiratory, Divison of Medicine, University College London, London, UK9 Allergy Department, 2nd Paediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece7 Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UKDepartment of Medicine, Section of Respiratory Medicine, Gentofte University Hospital, Hellerup, Denmark5 Centre for Reviews and Dissemination, University of York, York, UK7 Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK7 Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK3 Population Health Research Institute, St George’s University of London, London, UK8 North West School of Intensive Care Medicine, Health Education England North West, Manchester, UK10 Vocal, Manchester University NHS Foundation Trust, Manchester, UK1 Research and Innovation, Manchester University NHS Foundation Trust, Manchester, UK5 Centre for Reviews and Dissemination, University of York, York, UK2 Centre for Biostatistics, The University of Manchester, Manchester, UK6 Department of Respiratory Medicine and Infectious Diseases, Copenhagen University Hospital—Bispebjerg and Frederiksberg, Copenhagen University Hospital, Kobenhavn, Denmark12 North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK10 Vocal, Manchester University NHS Foundation Trust, Manchester, UK10 Vocal, Manchester University NHS Foundation Trust, Manchester, UK10 Vocal, Manchester University NHS Foundation Trust, Manchester, UKIntroduction Inhaled corticosteroids (ICS) can improve clinical outcomes in patients with chronic obstructive pulmonary disease (COPD) and eosinophilic airway inflammation, but they also increase the risk of side effects like pneumonia. Blood eosinophils guide ICS use, though evidence is limited. The predictors of treatment REsponse to ICS in COPD: a randomised controlled trials (RCTs) individual participant Data re-Evaluation (ICS-RECODE) research programme will leverage data from large RCTs to identify patients who benefit most from ICS with minimal risk. This protocol details an individual participant data (IPD) meta-analysis, assessing ICS safety, efficacy and treatment×covariate interactions to identify predictors of treatment response.Methods and analysis This meta-analysis will adhere to Cochrane, IPD handbook and Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance. We will conduct a two-stage IPD meta-analysis of RCTs evaluating the addition of ICS to maintenance COPD treatments. Only RCTs with at least 500 participants across all eligible arms will be included, to allow for treatment×covariate interaction evaluation. Primary outcomes are severe and moderate or severe exacerbation rates; secondary outcomes assess both safety and efficacy. Data from each RCT will be reanalysed using rigorous, consistent statistical methods. Treatment×covariate interactions will be assessed at the RCT level. Trial treatment effects and the coefficients of treatment×covariate interaction analyses will be pooled using random effects model meta-analysis. Risk of bias will be appraised using RoB-2 informed by IPD, and certainty of evidence will be assessed with GRADE and the Instrument to assess the Credibility of Effect Modification Analyses.The ICS-RECODE IPD meta-analysis will make use of the best available data to define evidence-based, precision medicine approaches for ICS use in COPD.Ethics and dissemination The Health Research Authority approved the ICS-RECODE study, exempting it from ethics review (HRA UK, Reference: 24/HRA/0460). Our findings will be published in peer-reviewed journals and shared with the scientific and broader stakeholder communities.PROSPERO registration number CRD42024508286.https://bmjopen.bmj.com/content/15/3/e095541.full |
| spellingShingle | Matthew Sperrin John R Hurst Michael Miligkos Joergen Vestbo Pradeesh Sivapalan Mike Clarke Lesley Stewart Jørgen Vestbo Dave Singh Tim Felton Alexander G Mathioudakis Rebecca Fortescue Jennifer Quint Jonathan Marshall Anurita Majumdar Jan Hansel Alice M Turner Sinduja Manohar Catherine Fullwood Nawar Diar Bakerly Mark Simmonds Steven Barnes Ashley Woodcock Sebastian Bate Jens-Ulrik Jensen Markus Fally Helen Ashdown Ashley A Woodcock Emily Howlett John Linnell Alan Preston Glauco Cappellini Dmitry Galkin Olaf Joens Predictors of treatment REsponse to inhaled corticosteroids (ICS) in Chronic Obstructive pulmonary disease: randomised controlled trials individual participant Data re-Evaluation–protocol of the ICS-RECODE individual participant data meta-analysis BMJ Open |
| title | Predictors of treatment REsponse to inhaled corticosteroids (ICS) in Chronic Obstructive pulmonary disease: randomised controlled trials individual participant Data re-Evaluation–protocol of the ICS-RECODE individual participant data meta-analysis |
| title_full | Predictors of treatment REsponse to inhaled corticosteroids (ICS) in Chronic Obstructive pulmonary disease: randomised controlled trials individual participant Data re-Evaluation–protocol of the ICS-RECODE individual participant data meta-analysis |
| title_fullStr | Predictors of treatment REsponse to inhaled corticosteroids (ICS) in Chronic Obstructive pulmonary disease: randomised controlled trials individual participant Data re-Evaluation–protocol of the ICS-RECODE individual participant data meta-analysis |
| title_full_unstemmed | Predictors of treatment REsponse to inhaled corticosteroids (ICS) in Chronic Obstructive pulmonary disease: randomised controlled trials individual participant Data re-Evaluation–protocol of the ICS-RECODE individual participant data meta-analysis |
| title_short | Predictors of treatment REsponse to inhaled corticosteroids (ICS) in Chronic Obstructive pulmonary disease: randomised controlled trials individual participant Data re-Evaluation–protocol of the ICS-RECODE individual participant data meta-analysis |
| title_sort | predictors of treatment response to inhaled corticosteroids ics in chronic obstructive pulmonary disease randomised controlled trials individual participant data re evaluation protocol of the ics recode individual participant data meta analysis |
| url | https://bmjopen.bmj.com/content/15/3/e095541.full |
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