Bibliographic study showed improving statistical methodology of network meta-analyses published between 1999 and 2015.

OBJECTIVES To assess the characteristics and core statistical methodology specific to network meta-analyses (NMAs) in clinical research articles. STUDY DESIGN AND SETTING We searched MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews from inception until April 14, 2015, for NMAs of randomized controlled trials including at least four different interventions. Two reviewers independently screened potential studies, whereas data abstraction was performed by a single reviewer and verified by a second. RESULTS A total of 456 NMAs, which included a median (interquartile range) of 21 (13-40) studies and 7 (5-9) treatment nodes, were assessed. A total of 125 NMAs (27%) were star networks; this proportion declined from 100% in 2005 to 19% in 2015 (P = 0.01 by test of trend). An increasing number of NMAs discussed transitivity or inconsistency (0% in 2005, 86% in 2015, P < 0.01) and 150 (45%) used appropriate methods to test for inconsistency (14% in 2006, 74% in 2015, P < 0.01). Heterogeneity was explored in 256 NMAs (56%), with no change over time (P = 0.10). All pairwise effects were reported in 234 NMAs (51%), with some increase over time (P = 0.02). The hierarchy of treatments was presented in 195 NMAs (43%), the probability of being best was most commonly reported (137 NMAs, 70%), but use of surface under the cumulative ranking curves increased steeply (0% in 2005, 33% in 2015, P < 0.01). CONCLUSION Many NMAs published in the medical literature have significant limitations in both the conduct and reporting of the statistical analysis and numerical results. The situation has, however, improved in recent years, in particular with respect to the evaluation of the underlying assumptions, but considerable room for further improvements remains.

[1]  Ethan M Balk,et al.  Influence of Reported Study Design Characteristics on Intervention Effect Estimates From Randomized, Controlled Trials , 2012, Annals of Internal Medicine.

[2]  Paula Williamson,et al.  Indirect Comparisons: A Review of Reporting and Methodological Quality , 2010, PloS one.

[3]  D. Altman,et al.  Measuring inconsistency in meta-analyses , 2003, BMJ : British Medical Journal.

[4]  Dan Jackson,et al.  A design-by-treatment interaction model for network meta-analysis with random inconsistency effects , 2014, Statistics in medicine.

[5]  Douglas G Altman,et al.  Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses , 2003, BMJ : British Medical Journal.

[6]  Simon G Thompson,et al.  Predicting the extent of heterogeneity in meta-analysis, using empirical data from the Cochrane Database of Systematic Reviews , 2012, International journal of epidemiology.

[7]  Douglas G Altman,et al.  Statistical methods for assessing the influence of study characteristics on treatment effects in ‘meta‐epidemiological’ research , 2002, Statistics in medicine.

[8]  Andrea Cipriani,et al.  Conceptual and Technical Challenges in Network Meta-analysis , 2013, Annals of Internal Medicine.

[9]  Douglas G Altman,et al.  Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study , 2010, BMJ : British Medical Journal.

[10]  Catrin Tudur Smith,et al.  Assessing key assumptions of network meta‐analysis: a review of methods , 2013, Research synthesis methods.

[11]  G. Lu,et al.  Assessing Evidence Inconsistency in Mixed Treatment Comparisons , 2006 .

[12]  Nicky J Welton,et al.  Automating network meta‐analysis , 2012, Research synthesis methods.

[13]  Ian R. White,et al.  Network Meta-analysis , 2015 .

[14]  Anna Chaimani,et al.  Using network meta‐analysis to evaluate the existence of small‐study effects in a network of interventions , 2012, Research synthesis methods.

[15]  Christopher H. Schmid,et al.  Characteristics of Networks of Interventions: A Description of a Database of 186 Published Networks , 2014, PloS one.

[16]  Douglas G Altman,et al.  Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study , 2008, BMJ : British Medical Journal.

[17]  J. Higgins,et al.  Empirical evidence about inconsistency among studies in a pair‐wise meta‐analysis , 2015, Research synthesis methods.

[18]  L. Trinquart,et al.  Influence of trial sample size on treatment effect estimates: meta-epidemiological study , 2013, BMJ : British Medical Journal.

[19]  Nicky J Welton,et al.  Network meta-analysis: a norm for comparative effectiveness? , 2015, The Lancet.

[20]  S Dias,et al.  Checking consistency in mixed treatment comparison meta‐analysis , 2010, Statistics in medicine.

[21]  J. McGowan,et al.  PRESS Peer Review of Electronic Search Strategies: 2015 Guideline Statement. , 2016, Journal of clinical epidemiology.

[22]  D. Cox,et al.  SOME QUICK SIGN TESTS FOR TREND IN LOCATION AND DISPERSION , 1955 .

[23]  Dimitris Mavridis,et al.  Publication bias and small-study effects magnified effectiveness of antipsychotics but their relative ranking remained invariant. , 2016, Journal of clinical epidemiology.

[24]  A. Sutton,et al.  Comparison of two methods to detect publication bias in meta-analysis. , 2006, JAMA.

[25]  Anna Chaimani,et al.  Visualizing Assumptions and Results in Network Meta-analysis: The Network Graphs Package , 2015 .

[26]  Alex J Sutton,et al.  Contour-enhanced meta-analysis funnel plots help distinguish publication bias from other causes of asymmetry. , 2008, Journal of clinical epidemiology.

[27]  Kristian Thorlund,et al.  The PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions: Checklist and Explanations , 2015, Annals of Internal Medicine.

[28]  Gerta Rücker,et al.  Ranking treatments in frequentist network meta-analysis works without resampling methods , 2015, BMC Medical Research Methodology.

[29]  Dimitris Mavridis,et al.  Characteristics of a loop of evidence that affect detection and estimation of inconsistency: a simulation study , 2014, BMC Medical Research Methodology.

[30]  Roger M. Harbord,et al.  Updated Tests for Small-study Effects in Meta-analyses , 2009 .

[31]  S D Walter,et al.  The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. , 1997, Journal of clinical epidemiology.

[32]  Dimitris Mavridis,et al.  A fully Bayesian application of the Copas selection model for publication bias extended to network meta‐analysis , 2013, Statistics in medicine.

[33]  Douglas G Altman,et al.  Methodological problems in the use of indirect comparisons for evaluating healthcare interventions: survey of published systematic reviews , 2009, BMJ : British Medical Journal.

[34]  J. Sterne,et al.  How important are comprehensive literature searches and the assessment of trial quality in systematic reviews? Empirical study. , 2003, Health technology assessment.

[35]  Julian P T Higgins,et al.  Evaluation of inconsistency in networks of interventions. , 2013, International journal of epidemiology.

[36]  Dimitris Mavridis,et al.  A primer on network meta-analysis with emphasis on mental health , 2015, Evidence-Based Mental Health.

[37]  Georgia Salanti,et al.  Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. , 2011, Journal of clinical epidemiology.

[38]  Deborah M Caldwell,et al.  Validity of indirect comparisons in meta-analysis , 2007, The Lancet.

[39]  Nicky J Welton,et al.  Effects of study precision and risk of bias in networks of interventions: a network meta-epidemiological study. , 2013, International journal of epidemiology.

[40]  Alex J Sutton,et al.  Inconsistency between direct and indirect comparisons of competing interventions: meta-epidemiological study , 2011, BMJ : British Medical Journal.

[41]  Harald Binder,et al.  A graphical tool for locating inconsistency in network meta-analyses , 2013, BMC Medical Research Methodology.

[42]  Tianjing Li,et al.  Network meta-analysis-highly attractive but more methodological research is needed , 2011, BMC medicine.

[43]  Huseyin Naci,et al.  Is network meta-analysis as valid as standard pairwise meta-analysis? It all depends on the distribution of effect modifiers , 2013, BMC Medicine.

[44]  Deborah M Caldwell,et al.  NICE DSU Technical Support Document 4: Inconsistency in Networks of Evidence Based on Randomised Controlled Trials. , 2011 .

[45]  Philippe Ravaud,et al.  Reporting of results from network meta-analyses: methodological systematic review , 2014, BMJ : British Medical Journal.

[46]  Georgia Salanti,et al.  Indirect and mixed‐treatment comparison, network, or multiple‐treatments meta‐analysis: many names, many benefits, many concerns for the next generation evidence synthesis tool , 2012, Research synthesis methods.

[47]  Joseph C Cappelleri,et al.  Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 1. , 2011, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[48]  Joseph C Cappelleri,et al.  Indirect treatment comparison/network meta-analysis study questionnaire to assess relevance and credibility to inform health care decision making: an ISPOR-AMCP-NPC Good Practice Task Force report. , 2014, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[49]  AE Ades,et al.  Consistency and inconsistency in network meta-analysis: concepts and models for multi-arm studies‡ , 2012, Research synthesis methods.

[50]  Andrew W Lee,et al.  Review of mixed treatment comparisons in published systematic reviews shows marked increase since 2009. , 2014, Journal of clinical epidemiology.

[51]  Alex J. Sutton,et al.  Evidence Synthesis for Decision Making 4 , 2013, Medical decision making : an international journal of the Society for Medical Decision Making.

[52]  Aaron N. Winn,et al.  An Assessment of the Methodological Quality of Published Network Meta-Analyses: A Systematic Review , 2015, PloS one.

[53]  S Duval,et al.  Trim and Fill: A Simple Funnel‐Plot–Based Method of Testing and Adjusting for Publication Bias in Meta‐Analysis , 2000, Biometrics.

[54]  Dan Jackson,et al.  Consistency and inconsistency in network meta-analysis: model estimation using multivariate meta-regression‡ , 2012, Research synthesis methods.

[55]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[56]  Johannes B Reitsma,et al.  GetReal in network meta‐analysis: a review of the methodology , 2016, Research synthesis methods.

[57]  Philippe Ravaud,et al.  Analysis of the systematic reviews process in reports of network meta-analyses: methodological systematic review , 2013, BMJ.

[58]  Julian P T Higgins,et al.  Recent developments in meta‐analysis , 2008, Statistics in medicine.

[59]  C. Begg,et al.  Operating characteristics of a rank correlation test for publication bias. , 1994, Biometrics.

[60]  Alex J. Sutton,et al.  Evidence Synthesis for Decision Making 7 , 2013, Medical decision making : an international journal of the Society for Medical Decision Making.

[61]  K R Abrams,et al.  Modelling publication bias in meta-analysis: a review. , 2000, Statistical methods in medical research.

[62]  Alex J. Sutton,et al.  Publication and related biases: a review , 2000 .

[63]  D. Kendrick,et al.  An exploration of synthesis methods in public health evaluations of interventions concludes that the use of modern statistical methods would be beneficial. , 2014, Journal of clinical epidemiology.

[64]  Christian Gluud,et al.  Reported Methodologic Quality and Discrepancies between Large and Small Randomized Trials in Meta-Analyses , 2001, Annals of Internal Medicine.

[65]  Panagiota Spyridonos,et al.  Graphical Tools for Network Meta-Analysis in STATA , 2013, PloS one.

[66]  K A L'Abbé,et al.  Meta-analysis in clinical research. , 1987, Annals of internal medicine.

[67]  Gerta Rücker,et al.  Network Meta-Analysis using Frequentist Methods , 2015 .

[68]  Alex J. Sutton,et al.  Evidence Synthesis for Decision Making 2 , 2013, Medical decision making : an international journal of the Society for Medical Decision Making.

[69]  Philippe Ravaud,et al.  Adjustment for reporting bias in network meta-analysis of antidepressant trials , 2012, BMC Medical Research Methodology.

[70]  T. Lumley Network meta‐analysis for indirect treatment comparisons , 2002, Statistics in medicine.

[71]  D G Altman,et al.  Indirect comparisons of competing interventions. , 2005, Health technology assessment.