Introduction to systematic reviews and meta‐analysis

Systematic reviews provide a method for collating and synthesizing research, and are used to inform healthcare decision making by clinicians, consumers and policy makers. A core component of many systematic reviews is a meta‐analysis , which is a statistical synthesis of results across studies. In this review article, we introduce meta‐analysis, focusing on the different meta‐analysis models, their interpretation, how a model should be selected and discuss potential threats to the validity of meta‐analyses. We illustrate the application of meta‐analysis using data from a review examining the effects of early use of inhaled corticosteroids in the emergency department treatment of acute asthma.

[1]  Douglas G Altman,et al.  Comparison of protocols and registry entries to published reports for randomised controlled trials. , 2011, The Cochrane database of systematic reviews.

[2]  S G Thompson,et al.  Systematic Review: Why sources of heterogeneity in meta-analysis should be investigated , 1994, BMJ.

[3]  S. Thompson,et al.  Detecting and describing heterogeneity in meta-analysis. , 1998, Statistics in medicine.

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

[5]  S. Thompson,et al.  How should meta‐regression analyses be undertaken and interpreted? , 2002, Statistics in medicine.

[6]  M. Sydes,et al.  Practical methods for incorporating summary time-to-event data into meta-analysis , 2007, Trials.

[7]  W. G. Cochran.  The combination of estimates from different experiments. , 1954 .

[8]  Rebecca M Turner,et al.  Characteristics of meta-analyses and their component studies in the Cochrane Database of Systematic Reviews: a cross-sectional, descriptive analysis , 2011, BMC medical research methodology.

[9]  David Moher,et al.  An international registry of systematic-review protocols , 2011, The Lancet.

[10]  Jonathan J Deeks,et al.  Issues in the selection of a summary statistic for meta‐analysis of clinical trials with binary outcomes , 2002, Statistics in medicine.

[11]  P. Sedgwick.  How to read a forest plot in a meta-analysis , 2015, BMJ : British Medical Journal.

[12]  D. Altman,et al.  Chapter 8: Assessing risk of bias in included studies , 2008 .

[13]  J. Higgins,et al.  Cochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0. The Cochrane Collaboration , 2013 .

[14]  Joseph Beyene,et al.  The ratio of means method as an alternative to mean differences for analyzing continuous outcome variables in meta-analysis: A simulation study , 2008 .

[15]  David J Spiegelhalter,et al.  A re-evaluation of random-effects meta-analysis , 2009, Journal of the Royal Statistical Society. Series A,.

[16]  M. Egger,et al.  The hazards of scoring the quality of clinical trials for meta-analysis. , 1999, JAMA.

[17]  Peter Herbison,et al.  Adjustment of meta-analyses on the basis of quality scores should be abandoned. , 2006, Journal of clinical epidemiology.

[18]  C. Camargo,et al.  Early use of inhaled corticosteroids in the emergency department treatment of acute asthma. , 2012, The Cochrane database of systematic reviews.

[19]  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.

[20]  J. Ioannidis,et al.  Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials , 2011, BMJ : British Medical Journal.

[21]  F Mosteller,et al.  Some Statistical Methods for Combining Experimental Results , 1990, International Journal of Technology Assessment in Health Care.

[22]  L. Hedges,et al.  Fixed- and random-effects models in meta-analysis. , 1998 .

[23]  Richard D Riley,et al.  Interpretation of random effects meta-analyses , 2011, BMJ : British Medical Journal.

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

[25]  Sally Hopewell,et al.  PRISMA for Abstracts: Reporting Systematic Reviews in Journal and Conference Abstracts , 2013, PLoS medicine.

[26]  Gordon H Guyatt,et al.  GRADE guidelines: 12. Preparing summary of findings tables-binary outcomes. , 2013, Journal of clinical epidemiology.

[27]  D L Demets,et al.  Methods for combining randomized clinical trials: strengths and limitations. , 1987, Statistics in medicine.

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

[29]  David Moher,et al.  Epidemiology and Reporting Characteristics of Systematic Reviews , 2007, PLoS medicine.

[30]  L. Hedges,et al.  Introduction to Meta‐Analysis , 2009, International Coaching Psychology Review.

[31]  Douglas G Bonett,et al.  Meta-analytic interval estimation for standardized and unstandardized mean differences. , 2009, Psychological methods.

[32]  Michael Borenstein,et al.  Meta-Analysis and Subgroups , 2013, Prevention Science.

[33]  D. Moher,et al.  An Evaluation of Epidemiological and Reporting Characteristics of Complementary and Alternative Medicine (CAM) Systematic Reviews (SRs) , 2013, PloS one.

[34]  P. Shekelle,et al.  Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation , 2016, British Medical Journal.

[35]  E. Faerstein,et al.  A DICTIONARY OF EPIDEMIOLOGY , 2016 .

[36]  C. Mulrow.  The medical review article: state of the science. , 1987, Annals of internal medicine.

[37]  H. Bastian,et al.  Seventy-Five Trials and Eleven Systematic Reviews a Day: How Will We Ever Keep Up? , 2010, PLoS medicine.

[38]  P. Jones,et al.  The St George's Respiratory Questionnaire. , 1991, Respiratory medicine.

[39]  George Davey Smith,et al.  meta-analysis bias in location and selection of studies , 1998 .

[40]  Douglas G. Altman,et al.  Evidence for the Selective Reporting of Analyses and Discrepancies in Clinical Trials: A Systematic Review of Cohort Studies of Clinical Trials , 2014, PLoS medicine.

[41]  S Greenland,et al.  Random-effects meta-analyses are not always conservative. , 1999, American journal of epidemiology.

[42]  N. Laird,et al.  Meta-analysis in clinical trials. , 1986, Controlled clinical trials.

[43]  Jonathan J Deeks,et al.  Much ado about nothing: a comparison of the performance of meta‐analytical methods with rare events , 2007, Statistics in medicine.

[44]  M. Egger,et al.  Bias in location and selection of studies. , 1998, BMJ.

[45]  Wolfgang Viechtbauer,et al.  Conducting Meta-Analyses in R with the metafor Package , 2010 .

[46]  J R Teagarden,et al.  Meta‐Analysis: Whither Narrative Review? , 1989, Pharmacotherapy.

[47]  J. Sterne,et al.  The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials , 2011, BMJ : British Medical Journal.

[48]  R. Wolfe,et al.  Modern statistical methods in respiratory medicine , 2014, Respirology.

[49]  D. Moher,et al.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. , 2010, International journal of surgery.

[50]  P. Gøtzsche.  Reporting of outcomes in arthritis trials measured on ordinal and interval scales is inadequate in relation to meta-analysis , 2001, Annals of the rheumatic diseases.

[51]  A R Feinstein,et al.  Meta-analysis: statistical alchemy for the 21st century. , 1995, Journal of clinical epidemiology.

[52]  Katja Jasinskaja,et al.  Elaboration and Explanation ⋆ , 2011 .

[53]  M. S. Patel,et al.  An introduction to meta-analysis. , 1989, Health Policy.

[54]  Hannah R Rothstein,et al.  A basic introduction to fixed‐effect and random‐effects models for meta‐analysis , 2010, Research synthesis methods.

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

[56]  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.

[57]  M. Leeflang,et al.  Cochrane diagnostic test accuracy reviews , 2013, Systematic Reviews.

[58]  Julian P T Higgins,et al.  Graphical displays for meta‐analysis: An overview with suggestions for practice , 2010, Research synthesis methods.

[59]  L. Hedges,et al.  The Handbook of Research Synthesis and Meta-Analysis , 2009 .

[60]  Douglas G. Altman,et al.  Chapter 9: Analysing Data and Undertaking Meta-Analyses , 2008 .

[61]  J. Neilson,et al.  Statistical methods can be improved within Cochrane pregnancy and childbirth reviews. , 2011, Journal of clinical epidemiology.

[62]  J. Higgins.  Cochrane handbook for systematic reviews of interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration , 2011 .

[63]  P. Shekelle,et al.  Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation , 2015, BMJ : British Medical Journal.

[64]  Ralf Bender,et al.  Methods to estimate the between‐study variance and its uncertainty in meta‐analysis† , 2015, Research synthesis methods.

[65]  E. Akl,et al.  Framing of health information messages. , 2011, The Cochrane database of systematic reviews.

[66]  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.

[67]  F. Song,et al.  Dissemination and publication of research findings: an updated review of related biases. , 2010, Health technology assessment.