Critical interpretation of pairwise and network meta-analysis of randomized respiratory clinical trials

Interpretazione critica delle “pairwise” e “network” meta-analisi di studi clinici randomizzati in ambito respiratorio




BPCO; broncodilatatori; corticosteroidi; farmacoterapia; meta-analisi.


A meta-analysis is a statistical technique used to assess the data of   independent studies concerning the same clinical scenario, in order to  synthesize results that are reported as effect estimate. The strength of a meta-analysis lies in its potential to combine the results of   studies characterized by different size and that may have been   underpowered to answer clinically relevant questions. Furthermore, meta-analyses can be used to clarify questions for which large randomized controlled trials have not led to consensus within the scientific community. The effect estimate resulting from a meta-analysis should be interpreted both from a statistical and clinical point of view. The clinical interpretation of the effect estimate must take into consideration the minimal clinically important differences compared to the comparator, which may be placebo and/or other active treatments. In this review we consider the key points needed to correctly and critically interpret the current meta-analyses, and to assess how reliable are the results from a statistical and clinical point of view.



Download data is not yet available.


Smith ML, Glass GV. Meta-analysis of psychotherapy outcome studies. Am Psychol. 1977;32(9):752-60.

Cazzola M, Rogliani P, Calzetta L, Matera MG. Triple therapy versus single and dual long-acting bronchodilator therapy in COPD: a systematic review and meta-analysis. Eur Respir J. 2018;52(6). pii: 1801586. doi: 10.1183/13993003.01586-2018

Cazzola M, Calzetta L, Barnes PJ et al. Efficacy and safety profile of xanthines in COPD: a network meta-analysis. Eur Respir Rev. 2018;27(148). pii: 180010.

Cazzola M, Calzetta L, Rogliani P et al. Impact of doxofylline in COPD: a pairwise meta-analysis. Pulm Pharmacol Ther. 2018;51:1-9.

Calzetta L, Ora J, Cavalli F et al. Impact of LABA/LAMA combination on exercise endurance and lung hyperinflation in COPD: a pair-wise and network meta-analysis. Respir Med. 2017;129:189-98.

Cazzola M, Rogliani P, Calzetta L et al. Impact of mucolytic agents on COPD exacerbations: a pair-wise and network meta-analysis. COPD. 2017;14(5):552-63.

Rogliani P, Calzetta L, Cavalli F et al. Pirfenidone, nintedanib and N-acetylcysteine for the treatment of idiopathic pulmonary fibrosis: a systematic review and meta-analysis. Pulm Pharmacol Ther. 2016;40:95-103.

Calzetta L, Rogliani P, Ora J et al. LABA/LAMA combination in COPD: a meta-analysis on the duration of treatment. Eur Respir Rev. 2017;26(143) pii: 160043.

Calzetta L, Matera MG, Braido F et al. Withdrawal of inhaled corticosteroids in COPD: a meta-analysis. Pulm Pharmacol Ther. 2017;45:148-58.

Cazzola M, Calzetta L, Rogliani P, Matera MG. Tiotropium formulations and safety: a network meta-analysis. Ther Adv Drug Saf. 2017;8(1):17-30.

Rogliani P, Calzetta L, Cazzola M, Matera MG. Drug safety evaluation of roflumilast for the treatment of COPD: a meta-analysis. Expert Opin Drug Saf. 2016;15(8):1133-46.

Calzetta L, Rogliani P, Matera MG, Cazzola M. A systematic review with meta-analysis of dual bronchodilation with LAMA/LABA for the treatment of stable COPD. Chest. 2016;149(5):1181-96.

Cazzola M, Calzetta L, Page C et al. Influence of N-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis. Eur Respir Rev. 2015;24(137):451-61.

Rogliani P, Matera MG, Ora J et al. The impact of dual bronchodilation on cardiovascular serious adverse events and mortality in COPD: a quantitative synthesis. Int J Chron Obstruct Pulmon Dis. 2017;12:3469-85.

Calzetta L, Cazzola M, Matera MG, Rogliani P. Adding a LAMA to ICS/LABA therapy: a meta-analysis of triple combination therapy in COPD. Chest. 2019;155(4):758-70.

Moher D, Shamseer L, Clarke M et al.; PRISMA-P Group. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015;4:1.

Cazzola M, MacNee W, Martinez FJ et al.; American Thoracic Society; European Respiratory Society Task Force on outcomes of COPD. Outcomes for COPD pharmacological trials: from lung function to biomarkers. Eur Respir J. 2008;31(2):416-69.

Magnussen H, Disse B, Rodriguez-Roisin R et al.; WISDOM Investigators. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. N Engl J Med. 2014;371(14):1285-94.

Guyatt GH, Oxman AD, Kunz R et al. GRADE guidelines 6. Rating the quality of evidence--imprecision. J Clin Epidemiol. 2011;64(12):1283-93.

Bateman E; SHINE study report authors. Lack of clinically relevant differences between combination therapy and monotherapy in COPD. Eur Respir J. 2014;43(4):1204-5.

Pedder H, Sarri G, Keeney E et al. Data extraction for complex meta-analysis (DECiMAL) guide. Syst Rev. 2016;5(1):212.

Higgins JP, Altman DG, Gøtzsche PC et al.; Cochrane Bias Methods Group; Cochrane Statistical Methods Group. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.

Berger VW, Alperson SY. A general framework for the evaluation of clinical trial quality. Rev Recent Clin Trials. 2009;4(2):79-88.

Shamseer L, Moher D, Clarke M et al.; PRISMA-P Group. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015;350:g7647.

Haidich AB. Meta-analysis in medical research. Hippokratia. 2010;14(Suppl 1):29-37.

Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557-60.

Salanti G. Indirect and mixed-treatment comparison, network, or multiple-treatments meta-analysis: many names, many benefits, many concerns for the next generation evidence synthesis tool. Res Synth Methods. 2012;3(2):80-97.

Salanti G, Ades AE, Ioannidis JP. Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol. 2011;64(2):163-71.

Pearlman DS. Primum non nocere and "black box" warnings. J Allergy Clin Immunol. 2006;117(1):30-1.

Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629-34.

Guyatt G, Oxman AD, Akl EA et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64(4):383-94.



How to Cite

Rogliani, P., & Calzetta, L. (2019). Critical interpretation of pairwise and network meta-analysis of randomized respiratory clinical trials: Interpretazione critica delle “pairwise” e “network” meta-analisi di studi clinici randomizzati in ambito respiratorio. AboutOpen, 5(1), 55–61.
Received 2019-04-29
Accepted 2019-05-29
Published 2019-06-27