General principles for systematic reviews and meta-analyses and a critique of a recent systematic review of long-acting β-agonists

A systematic review attempts to summarize the scientific evidence related to treatment, causation, diagnosis, or prognosis of a specific disease. Meta-analysis refers to that portion of the systematic review that involves the statistical analysis. This perspective describes the appropriate steps in a systematic review and meta-analysis and critiques the recent systematic review on the effect of long-acting β-agonists on severe asthma exacerbations and asthma-related deaths. The authors of this systematic review identified 19 relevant studies and applied most of the methodological steps appropriately, although there is some concern about publication bias. The authors uncovered statistically significantly increased risk for long-acting β-agonists compared with placebo with respect to severe asthma exacerbations, life-threatening asthma exacerbations, and asthma-related deaths. Out of the 19 studies included in the systematic review, the Salmeterol Multicenter Asthma Research Trial provided 80% of the data and dominated the meta-analysis component, especially with respect to asthma-related deaths.