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Open Access Highly Accessed Research article

Where is the supporting evidence for treating mild to moderate chronic obstructive pulmonary disease exacerbations with antibiotics? A systematic review

Milo A Puhan12*, Daniela Vollenweider1, Johann Steurer1, Patrick M Bossuyt3 and Gerben ter Riet4

Author Affiliations

1 Horten Centre for Patient-oriented Research and Knowledge Transfer, University of Zurich, Switzerland

2 Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, Johns Hopkins University, Baltimore (MD), USA

3 Academic Medical Center, Department of Clinical Epidemiology, Bioinformatics and Biostatistics, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands

4 Academic Medical Center, Department of General Practice, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands

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BMC Medicine 2008, 6:28  doi:10.1186/1741-7015-6-28

Published: 10 October 2008

Abstract

Background

Randomised trials comparing different drugs head-to-head are extremely valuable for clinical decision-making. However, it is scientifically and ethically sensible to demand strong evidence that a drug is effective by showing superiority over a placebo before embarking on head-to-head comparisons of potentially ineffective drugs. Our aim was to study the evolvement of evidence from placebo-controlled and head-to-head trials on the effects of antibiotics for the treatment of mild to moderate exacerbations of chronic obstructive pulmonary disease.

Methods

We conducted a historical systematic review. Through electronic databases and hand-searches, we identified placebo-controlled and head-to-head antibiotic trials for the treatment of mild to moderate chronic obstructive pulmonary disease exacerbations. We compared the numbers of patients recruited in placebo-controlled and head-to-head trials between 1957 and 2005. Using cumulative meta-analysis of placebo-controlled trials, we determined when, if ever, placebo-controlled trials had shown convincing evidence that antibiotics are effective in preventing treatment failure in patients with mild to moderate chronic obstructive pulmonary disease exacerbations.

Results

The first head-to-head trial was published in 1963. It was followed by another 100 trials comparing different antibiotics in a total of 34,029 patients with mild to moderate chronic obstructive pulmonary disease exacerbations. Over time, the cumulative odds ratio in placebo-controlled trials remained inconclusive throughout with odds ratios ranging from 0.39 (95% confidence intervals 0.04–4.22) to the most recent estimate (1995) of 0.81 (95% confidence intervals 0.52–1.28, P = 0.37).

Conclusion

Placebo-controlled trials do not support the use of antibiotics in chronic obstructive pulmonary disease patients with mild to moderate exacerbations. Conducting head-to-head trials is, therefore, scientifically and ethically questionable. This underscores the requirement to perform or study systematic reviews of placebo-controlled trials before conducting head-to-head trials.