James D Chalmers1, Melissa J McDonnell2, Robert Rutherford2, John Davidson3, Simon Finch4, Megan Crichton4, Lieven Dupont5, Adam T Hill6, Thomas C Fardon4, Anthony De Soyza3, Stefano Aliberti7, Pieter Goeminne8. 1. Scottish Centre for Respiratory Research, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. Electronic address: jchalmers@dundee.ac.uk. 2. Department of Respiratory Medicine, Galway University Hospitals, Newcastle Road, Galway, Ireland. 3. Institute of Cellular Medicine, Newcastle University and Adult Bronchiectasis Service Freeman Hospital Newcastle upon Tyne NE7 7DN, UK. 4. Scottish Centre for Respiratory Research, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. 5. University Hospital Gasthuisberg, Respiratory Medicine, Herestraat 49, B-3000 Leuven, Belgium. 6. Department of Respiratory Medicine, Royal Infirmary of Edinburgh and the University of Edinburgh, 51 Little France Crescent, Old Dalkeith Road, Edinburgh, EH16 4SA, UK. 7. Department of Health Science, University of Milan Bicocca, Clinica Pneumologica, AO San Gerardo, Via Pergolesi 33, Monza, Italy. 8. University Hospital Gasthuisberg, Respiratory Medicine, Herestraat 49, B-3000 Leuven, Belgium; Department of Respiratory Medicine, AZ Nikolaas, Sint-Niklaas, Belgium.
Abstract
INTRODUCTION: 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). CONCLUSION: 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.
INTRODUCTION: 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). CONCLUSION: 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: Hamdan Al-Jahdali; Abdullah Alshimemeri; Abdullah Mobeireek; Amr S Albanna; Nehad N Al Shirawi; Siraj Wali; Khaled Alkattan; Abdulrahman A Alrajhi; Khalid Mobaireek; Hassan S Alorainy; Mohamed S Al-Hajjaj; Anne B Chang; Stefano Aliberti Journal: Ann Thorac Med Date: 2017 Jul-Sep Impact factor: 2.219
Authors: David de la Rosa Carrillo; Rodrigo Athanazio; Rosa Maria Girón Moreno; Luis Máiz Carro; Casilda Olveira; Javier de Gracia; Montserrat Vendrell; Concepción Prados Sánchez; Georgina Gramblicka; Monica Corso Pereira; Fernando Lundgren; Mara Fernandes De Figueiredo; Francisco Arancibia; Samia Rached; Miguel-Angel Martínez-Garcia Journal: ERJ Open Res Date: 2018-03-06
Authors: Andrea Gramegna; Stefano Aliberti; Manuela Seia; Luigi Porcaro; Vera Bianchi; Carlo Castellani; Paola Melotti; Claudio Sorio; Enza Consalvo; Elisa Franceschi; Francesco Amati; Martina Contarini; Michele Gaffuri; Luca Roncoroni; Barbara Vigone; Angela Bellofiore; Cesare Del Monaco; Martina Oriano; Leonardo Terranova; Maria Francesca Patria; Paola Marchisio; Baroukh M Assael; Francesco Blasi Journal: Multidiscip Respir Med Date: 2018-08-09
Authors: Jacob Twiss; Alistair Stewart; Catherine A Gilchrist; Jeffrey A Keelan; Russell Metcalfe; Catherine A Byrnes Journal: J Paediatr Child Health Date: 2022-02-16 Impact factor: 1.929
Authors: James D Chalmers; Megan Crichton; Pieter C Goeminne; Michael R Loebinger; Charles Haworth; Marta Almagro; Montse Vendrell; Anthony De Soyza; Raja Dhar; Lucy Morgan; Francesco Blasi; Stefano Aliberti; Jeanette Boyd; Eva Polverino Journal: Breathe (Sheff) Date: 2017-09
Authors: James D Chalmers; Alan Timothy; Eva Polverino; Marta Almagro; Thomas Ruddy; Pippa Powell; Jeanette Boyd Journal: Breathe (Sheff) Date: 2017-09