title: The generalizability of bronchiectasis randomized controlled trials: A multicentre cohort study.
abstract: BACKGROUND
  Randomized controlled trials (RCTs) for bronchiectasis have experienced difficulties with recruitment and in reaching their efficacy end-points. To estimate the generalizability of such studies we applied the eligibility criteria for major RCTs in bronchiectasis to 6 representative observational European Bronchiectasis cohorts.
  
  
  METHODS
  Inclusion and exclusion criteria from 10 major RCTs were applied in each cohort. Demographics and outcomes were compared between patients eligible and ineligible for RCTs.
  
  
  RESULTS
  1672 patients were included. On average 33.0% were eligible for macrolide trials, 15.0% were eligible for inhaled antibiotic trials, 15.9% for the DNAse study and 47.7% were eligible for a study of dry powder mannitol. Within these groups, some trials were highly selective with only 1-9% of patients eligible. Eligible patients were generally more severe with higher mortality during follow-up (mean 17.2 vs 9.0% for macrolide studies, 19.2%% vs 10.7% for inhaled antibiotic studies), and a higher frequency of exacerbations than ineligible patients. As up to 93% of patients were ineligible for studies, however, numerically more deaths and exacerbations occurred in ineligible patient across studies (mean 56% of deaths occurred in ineligible patients across all studies).
  
  
  CONCLUSIONS
  Our data suggest that patients enrolled in RCT's in bronchiectasis are only partially representative of patients in clinical practice. The majority of mortality and morbidity in bronchiectasis occurs in patients ineligible for many current trials.
authors: Scottish Centre for Respiratory Research, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. Electronic address: jchalmers@dundee.ac.uk.
authors: James D
authors: JD
authors: Chalmers
authors: Department of Respiratory Medicine, Galway University Hospitals, Newcastle Road, Galway, Ireland.
authors: Melissa J
authors: MJ
authors: McDonnell
authors: Department of Respiratory Medicine, Galway University Hospitals, Newcastle Road, Galway, Ireland.
authors: Robert
authors: R
authors: Rutherford
authors: Institute of Cellular Medicine, Newcastle University and Adult Bronchiectasis Service Freeman Hospital Newcastle upon Tyne NE7 7DN, UK.
authors: John
authors: J
authors: Davidson
authors: Scottish Centre for Respiratory Research, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK.
authors: Simon
authors: S
authors: Finch
authors: Scottish Centre for Respiratory Research, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK.
authors: Megan
authors: M
authors: Crichton
authors: University Hospital Gasthuisberg, Respiratory Medicine, Herestraat 49, B-3000 Leuven, Belgium.
authors: Lieven
authors: L
authors: Dupont
authors: Department of Respiratory Medicine, Royal Infirmary of Edinburgh and the University of Edinburgh, 51 Little France Crescent, Old Dalkeith Road, Edinburgh, EH16 4SA, UK.
authors: Adam T
authors: AT
authors: Hill
authors: Scottish Centre for Respiratory Research, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK.
authors: Thomas C
authors: TC
authors: Fardon
authors: Institute of Cellular Medicine, Newcastle University and Adult Bronchiectasis Service Freeman Hospital Newcastle upon Tyne NE7 7DN, UK.
authors: Anthony
authors: A
authors: De Soyza
authors: Department of Health Science, University of Milan Bicocca, Clinica Pneumologica, AO San Gerardo, Via Pergolesi 33, Monza, Italy.
authors: Stefano
authors: S
authors: Aliberti
authors: University Hospital Gasthuisberg, Respiratory Medicine, Herestraat 49, B-3000 Leuven, Belgium; Department of Respiratory Medicine, AZ Nikolaas, Sint-Niklaas, Belgium.
authors: Pieter
authors: P
authors: Goeminne
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001987:Bronchiectasis / Q000188:drug therapy*; D015331:Cohort Studies; D003851:Deoxyribonucleases / Q000627:therapeutic use*; D004234:Diuretics, Osmotic / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008353:Mannitol / Q000627:therapeutic use*; D008875:Middle Aged; D018579:Patient Selection; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index
chemical_list: D000900:Anti-Bacterial Agents; D004234:Diuretics, Osmotic; D008353:Mannitol; D003851:Deoxyribonucleases
keywords: Antibiotics; Bronchiectasis; Clinical trials; Evidence-based medicine