The generalizability of bronchiectasis randomized controlled trials: A multicentre cohort study - 27/02/16
, Melissa J. McDonnell b, Robert Rutherford b, John Davidson c, Simon Finch a, Megan Crichton a, Lieven Dupont d, Adam T. Hill e, Thomas C. Fardon a, Anthony De Soyza c, Stefano Aliberti f, Pieter Goeminne d, gAbstract |
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.
Le texte complet de cet article est disponible en PDF.Highlights |
• | A number of recent bronchiectasis trials have failed to meet their primary end-point. It is important to determine if patients included in trials are representative of the populations to which intervention will be applied to in the future. In this study we evaluated the generalisability of bronchiectasis clinical trials. We identified that the majority of bronchiectasis trials were highly selective and did not take account of the profound heterogeneity of the disease. |
• | We identified that the majority of medical treatments currently being developed for bronchiectasis are targeted at the most severe patients and those with chronic airway colonisation. While this may be appropriate for certain therapies, we highlight that the burden of disease remains high in the large group of patients currently excluded from trials. |
• | We propose that in some cases, regulators and drug developers should look to using less stringent inclusion criteria and thereby produce therapies that can be of benefit to larger groups of patients. |
Keywords : Bronchiectasis, Clinical trials, Evidence-based medicine, Antibiotics
Plan
Vol 112
P. 51-58 - mars 2016 Retour au numéro
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