Meta-analysis in medical research.

The objectives of this paper are to provide an introduction to meta-analysis and to discuss the rationale for this type of research and other general considerations. Methods used to produce a rigorous meta-analysis are highlighted and some aspects of presentation and interpretation of meta-analysis are discussed.Meta-analysis is a quantitative, formal, epidemiological study design used to systematically assess previous research studies to derive conclusions about that body of research. Outcomes from a meta-analysis may include a more precise estimate of the effect of treatment or risk factor for disease, or other outcomes, than any individual study contributing to the pooled analysis. The examination of variability or heterogeneity in study results is also a critical outcome. The benefits of meta-analysis include a consolidated and quantitative review of a large, and often complex, sometimes apparently conflicting, body of literature. The specification of the outcome and hypotheses that are tested is critical to the conduct of meta-analyses, as is a sensitive literature search. A failure to identify the majority of existing studies can lead to erroneous conclusions; however, there are methods of examining data to identify the potential for studies to be missing; for example, by the use of funnel plots. Rigorously conducted meta-analyses are useful tools in evidence-based medicine. The need to integrate findings from many studies ensures that meta-analytic research is desirable and the large body of research now generated makes the conduct of this research feasible.

[1]  I. Olkin,et al.  Meta-analysis of observational studies in epidemiology - A proposal for reporting , 2000 .

[2]  L. Stewart,et al.  Practical methodology of meta-analyses (overviews) using updated individual patient data. Cochrane Working Group. , 1995, Statistics in medicine.

[3]  S. Thompson,et al.  Quantifying heterogeneity in a meta‐analysis , 2002, Statistics in medicine.

[4]  Ingram Olkin,et al.  A method for the meta‐analysis of mutually exclusive binary outcomes , 2008, Statistics in medicine.

[5]  Thomas A Trikalinos,et al.  Meta-analysis methods. , 2008, Advances in genetics.

[6]  K. Dickersin,et al.  Meta-analysis: state-of-the-science. , 1992, Epidemiologic reviews.

[7]  Peter Jüni,et al.  Direction and impact of language bias in meta-analyses of controlled trials: empirical study. , 2002, International journal of epidemiology.

[8]  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.

[9]  R. Koff,et al.  Meta-analysis, decision analysis, and cost-effectiveness analysis. Methods for quantitative synthesis in medicine , 1995 .

[10]  J. Lau,et al.  State of the evidence: current status and prospects of meta-analysis in infectious diseases. , 1999, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

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

[12]  Jonathan J Deeks,et al.  Systematic reviews in health care: Systematic reviews of evaluations of diagnostic and screening tests. , 2001, BMJ.

[13]  Donald A. Berry,et al.  Meta-Analysis in Medicine and Health Policy , 2000 .

[14]  C D Naylor,et al.  Meta-analysis and the meta-epidemiology of clinical research , 1997, BMJ.

[15]  C H Schmid,et al.  Cumulative meta-analysis of clinical trials builds evidence for exemplary medical care. , 1995, Journal of clinical epidemiology.

[16]  S Greenland,et al.  Invited commentary: a critical look at some popular meta-analytic methods. , 1994, American journal of epidemiology.

[17]  Chandler Stolp,et al.  Summing Up: The Science of Reviewing Research , 1984 .

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

[19]  D. DeMets,et al.  Doing more good than harm: need for a cease fire. , 2009, The American journal of medicine.

[20]  Johannes B Reitsma,et al.  Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. , 2005, Journal of clinical epidemiology.

[21]  Richard D Riley,et al.  Beyond the Bench: Hunting Down Fugitive Literature , 2004, Environmental Health Perspectives.

[22]  Mark C Simmonds,et al.  Meta-analysis of individual patient data from randomized trials: a review of methods used in practice , 2005, Clinical trials.

[23]  L. Stewart,et al.  From science to practice. Meta-analyses using individual patient data are needed. , 1995 .

[24]  R J Cook,et al.  Users' guides to the medical literature. IX. A method for grading health care recommendations. Evidence-Based Medicine Working Group. , 1995, JAMA.

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

[26]  R. Peto,et al.  Beta blockade during and after myocardial infarction: an overview of the randomized trials. , 1985, Progress in cardiovascular diseases.

[27]  J. Bailar.  The promise and problems of meta-analysis. , 1997, The New England journal of medicine.

[28]  I. Olkin,et al.  The case of the misleading funnel plot , 2006, BMJ : British Medical Journal.

[29]  Douglas G Altman,et al.  The effects of excluding patients from the analysis in randomised controlled trials: meta-epidemiological study , 2009, BMJ : British Medical Journal.

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

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

[32]  George Davey Smith,et al.  Meta-analysis: Principles and procedures , 1997, BMJ.

[33]  G. Guyatt,et al.  The Science of Reviewing Research a , 1993, Annals of the New York Academy of Sciences.

[34]  G. Glass.  Primary, Secondary, and Meta-Analysis of Research1 , 1976 .

[35]  J. Ioannidis,et al.  Effect of early patient enrollment on the time to completion and publication of randomized controlled trials. , 2001, American journal of epidemiology.

[36]  J. Ioannidis.  Effect of the statistical significance of results on the time to completion and publication of randomized efficacy trials. , 1998, JAMA.

[37]  J. Sterne,et al.  Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis. , 2001, Journal of clinical epidemiology.

[38]  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.

[39]  J. Ioannidis,et al.  Mortality in systemic sclerosis: an international meta-analysis of individual patient data. , 2005, The American journal of medicine.

[40]  C D Naylor,et al.  Meta-analysis of controlled clinical trials. , 1989, The Journal of rheumatology.

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

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

[43]  S Greenland,et al.  Quantitative methods in the review of epidemiologic literature. , 1987, Epidemiologic reviews.

[44]  T C Chalmers,et al.  Evidence favoring the use of anticoagulants in the hospital phase of acute myocardial infarction. , 1977, The New England journal of medicine.

[45]  Douglas G Altman,et al.  Systematic reviews of evaluations of prognostic variables , 2001, BMJ : British Medical Journal.

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

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

[48]  J. Ioannidis,et al.  Systematic Review of the Empirical Evidence of Study Publication Bias and Outcome Reporting Bias , 2008, PloS one.

[49]  J. Ioannidis,et al.  Comparison of evidence of treatment effects in randomized and nonrandomized studies. , 2001, JAMA.

[50]  J. Hilden,et al.  Impact of allocation concealment on conclusions drawn from meta-analyses of randomized trials. , 2007, International journal of epidemiology.

[51]  Douglas G Altman,et al.  Systematic reviews in health care: Assessing the quality of controlled clinical trials. , 2001, BMJ.

[52]  C M Rutter,et al.  A hierarchical regression approach to meta‐analysis of diagnostic test accuracy evaluations , 2001, Statistics in medicine.

[53]  J. Ioannidis,et al.  Predictive modeling and heterogeneity of baseline risk in meta-analysis of individual patient data. , 2001, Journal of clinical epidemiology.

[54]  F. Mosteller,et al.  A comparison of results of meta-analyses of randomized control trials and recommendations of clinical experts. Treatments for myocardial infarction. , 1992, JAMA.

[55]  J. L. Tang,et al.  Misleading funnel plot for detection of bias in meta-analysis. , 2000, Journal of clinical epidemiology.

[56]  L E Moses,et al.  Estimating Diagnostic Accuracy from Multiple Conflicting Reports , 1993, Medical decision making : an international journal of the Society for Medical Decision Making.

[57]  G. Smith,et al.  Bias in meta-analysis detected by a simple, graphical test , 1997, BMJ.

[58]  L. Arends.  Multivariate meta-analysis: modelling the heterogeneity mixing apples and oranges; dangerous or delicious? , 2006 .

[59]  M. Hanefeld,et al.  Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial , 2009, The Lancet.

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

[61]  I. Tirodimos,et al.  The quality of safety reporting in trials is still suboptimal: survey of major general medical journals. , 2011, Journal of clinical epidemiology.

[62]  S. Nissen,et al.  Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. , 2007, The New England journal of medicine.

[63]  G. Guyatt,et al.  Users' Guides to the Medical Literature: IX. A Method for Grading Health Care Recommendations , 1995 .

[64]  J. Ioannidis,et al.  Quantitative Synthesis in Systematic Reviews , 1997, Annals of Internal Medicine.

[65]  D. Sackett,et al.  Evidence based medicine: what it is and what it isn't , 1996, BMJ.

[66]  Dan Jackson,et al.  A new approach to outliers in meta-analysis , 2008, Health care management science.

[67]  A. Hrõbjartsson,et al.  Empirical evidence for selective reporting of outcomes in randomized trials: comparison of protocols to published articles. , 2004, JAMA.

[68]  D. G. Altman,et al.  Statistical aspects of prognostic factor studies in oncology. , 1994, British Journal of Cancer.

[69]  Tania B. Huedo-Medina,et al.  Assessing heterogeneity in meta-analysis: Q statistic or I2 index? , 2006, Psychological methods.

[70]  C. Lengeler,et al.  Language bias in randomised controlled trials published in English and German , 1997, The Lancet.

[71]  W. Haenszel,et al.  Statistical aspects of the analysis of data from retrospective studies of disease. , 1959, Journal of the National Cancer Institute.

[72]  G. Grégoire,et al.  Discrepancies between meta-analyses and subsequent large randomized, controlled trials. , 1997, The New England journal of medicine.