Meta-analysis: Fact or fiction? How to interpret meta-analyses

Abstract Objectives. Widespread use of increasingly complex statistical methods makes it ever more challenging to adequately assess the results reported and conclusions drawn in meta-analytic research. This paper aims to identify potential fallacies by in-depth examination of recent publications on mood disorders. Methods. Three meta-analyses were selected based on availability of data and representativeness of methods employed. By means of detailed re-analysis, several widespread methodological problems were identified, and the example data were used to illustrate and discuss them. Results. General points addressed include clear formulation of the research question, choice of effect size measures, and general choice of model. Data quality problems like missing data and publication bias are discussed along with methods to deal with them. Furthermore, aspects of meta-analytic modelling like the use of fixed or random effects, data aggregation, as well as the use of subgroups are explained, and issues of excessive complexity and data dredging pointed out. Finally, the benefit of diagnostic tools like confidence bands and the importance of transparency regarding data and methodology for the interpretation of meta-analytic results are highlighted. Conclusions. Practically relevant quality criteria for readers to bear in mind when dealing with meta-analytic publications are summarized in a ten point checklist.

[1]  J. Ioannidis,et al.  Relative Citation Impact of Various Study Designs in the Health Sciences , 2005, JAMA.

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

[3]  J. Brooks Why most published research findings are false: Ioannidis JP, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece , 2008 .

[4]  H. Möller,et al.  Evidence-based medicine in psychopharmacotherapy: possibilities, problems and limitations , 2010, European Archives of Psychiatry and Clinical Neuroscience.

[5]  L. Simpson Report on Certain Enteric Fever Inoculation Statistics , 1904, British medical journal.

[6]  Amit X Garg,et al.  Systematic review and meta-analysis: when one study is just not enough. , 2008, Clinical journal of the American Society of Nephrology : CJASN.

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

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

[9]  H. Möller,et al.  How to grade categories of evidence , 2008, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[10]  Mark Petticrew,et al.  Systematic reviews from astronomy to zoology: myths and misconceptions , 2001, BMJ : British Medical Journal.

[11]  D. Bennett How can I deal with missing data in my study? , 2001, Australian and New Zealand journal of public health.

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

[13]  H. Möller,et al.  Meta-analyses: a method to maximise the evidence from clinical studies? , 2010, European Archives of Psychiatry and Clinical Neuroscience.

[14]  L. Hedges,et al.  The power of statistical tests in meta-analysis. , 2001, Psychological methods.

[15]  B. V. Zwieten-Boot,et al.  A regulatory Apologia — A review of placebo-controlled studies in regulatory submissions of new-generation antidepressants , 2008, European Neuropsychopharmacology.

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

[17]  J. Racoosin,et al.  Suicidality in pediatric patients treated with antidepressant drugs. , 2006, Archives of general psychiatry.

[18]  R. Sysko,et al.  Placebo response in studies of major depression: variable, substantial, and growing. , 2002, JAMA.

[19]  H. Möller,et al.  Principle standards and problems regarding proof of efficacy in clinical psychopharmacology , 2010, European Archives of Psychiatry and Clinical Neuroscience.

[20]  Robyn M Leventhal,et al.  Severity of Depression and Response to Antidepressants and Placebo: An Analysis of the Food and Drug Administration Database , 2002, Journal of clinical psychopharmacology.

[21]  P. Boyle,et al.  Beyond classical meta-analysis: can inadequately reported studies be included? , 2004, Drug discovery today.

[22]  L. Stewart,et al.  To IPD or not to IPD? , 2002, Evaluation & the health professions.

[23]  R. Hansen,et al.  Controlling for Drug Dose in Systematic Review and Meta-Analysis: A Case Study of the Effect of Antidepressant Dose , 2009, Medical decision making : an international journal of the Society for Medical Decision Making.

[24]  Blair T. Johnson,et al.  Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration , 2008, PLoS medicine.

[25]  Jacob Cohen Statistical Power Analysis for the Behavioral Sciences , 1969, The SAGE Encyclopedia of Research Design.

[26]  B. Beermann,et al.  Evidence b(i)ased medicine—selective reporting from studies sponsored by pharmaceutical industry: review of studies in new drug applications , 2003, BMJ : British Medical Journal.

[27]  J. Schölmerich Evidence B(i)ased Medicine , 2000, Clinical Oral Investigations.

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

[29]  Ingram Olkin,et al.  Adjusting for publication bias in the presence of heterogeneity , 2003, Statistics in medicine.

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

[31]  J. Geddes,et al.  Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis , 2009, The Lancet.

[32]  H. Möller,et al.  Efficacy of antidepressants: a re-analysis and re-interpretation of the Kirsch data. , 2011, The international journal of neuropsychopharmacology.

[33]  J. Ioannidis,et al.  The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. , 2009, Journal of clinical epidemiology.

[34]  Ian R White,et al.  Imputation methods for missing outcome data in meta-analysis of clinical trials , 2008, Clinical trials.

[35]  D. Moher,et al.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement , 2009, BMJ.

[36]  Andrea Cipriani,et al.  Imputing missing standard deviations in meta-analyses can provide accurate results. , 2006, Journal of clinical epidemiology.

[37]  David Rindskopf,et al.  Design makes a difference: a meta-analysis of antidepressant response rates in placebo-controlled versus comparator trials in late-life depression. , 2008, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[38]  A E Ades,et al.  The Interpretation of Random-Effects Meta-Analysis in Decision Models , 2005, Medical decision making : an international journal of the Society for Medical Decision Making.

[39]  Dan Jackson,et al.  The power of the standard test for the presence of heterogeneity in meta‐analysis , 2006, Statistics in medicine.

[40]  R. Waldmann,et al.  Placebo, Prozac and PLoS: significant lessons for psychopharmacology , 2011, Journal of psychopharmacology.

[41]  Larry V Hedges,et al.  The power of statistical tests for moderators in meta-analysis. , 2004, Psychological methods.

[42]  N. Freemantle,et al.  Early onset of selective serotonin reuptake inhibitor antidepressant action: systematic review and meta-analysis. , 2006, Archives of general psychiatry.

[43]  P. Gøtzsche,et al.  Antidepressant Drug Effects and Depression Severity: A , 2010 .

[44]  I. Olkin,et al.  Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement , 1999, The Lancet.

[45]  R. Poole,et al.  Selective publication of antidepressant trials. , 2008, The New England journal of medicine.

[46]  D Tritchler,et al.  Modelling study quality in meta-analysis. , 1999, Statistics in medicine.

[47]  R. Bausell,et al.  The Growth of Health-Related Meta-Analyses Published from 1980 to 2000 , 2001, Evaluation & the health professions.

[48]  Lucas M. Bachmann,et al.  An empirical comparison of methods for meta-analysis of diagnostic accuracy showed hierarchical models are necessary. , 2008, Journal of clinical epidemiology.

[49]  P C Lambert,et al.  A comparison of summary patient-level covariates in meta-regression with individual patient data meta-analysis. , 2002, Journal of clinical epidemiology.

[50]  R. DeRubeis,et al.  Bias resulting from the use of ‘assay sensitivity’ as an inclusion criterion for meta‐analysis , 2006, Statistics in medicine.

[51]  J. Calabrese,et al.  Lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression of individual patient data from five randomised trials , 2009, British Journal of Psychiatry.

[52]  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.