Meta-analysis in medical research

Abstract

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.

Keywords: bias; evidence-based medicine; meta-analysis; quality; randomized clinical trial; systematic review.

Figure 1:. Hierarchy of evidence

Figure 2:. Cumulative number of publications about metaanalysis over time, until 17 December 2009 (results from Medline search using text "meta-analysis")

Figure 3:. PRISMA 2009 Flow Diagram (From Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 2009;62:1006-12, For more information, visit www.prisma-statement.org)

Figure 4:. Forest plots of the meta-analysis addressing the use of antibiotic prophylaxis compared with no treatment in colon surgery. The outcome is would infection and 32 studies were included in the meta-analysis. Risk ratio <1 favors use of prophylactic antibiotics, whereas risk ratio > 1 suggests that no treatment is better. Left panel, Studies displayed chronologically by year of publication, n represents study size. Each study is represented by a filled circle (denoting its risk ratio estimate) and the horizontal line denotes the corresponding 95% confidence interval. Studies that intersect the vertical line of unity (RR=1), indicate no difference between the antibiotic group and the control group. Pooled results from all studies are shown at bottom with the random-effect model. Right panel,Cumulative meta-analysis of same studies with random-effects model, where the summary risk ratio is re-estimated each time a study is added over time. It reveals that antibiotic prophylaxis efficacy could have been identified as early as 1971 after 5 studies involving about 300 patients (n in this panel represents cumulative number of patients from included studies). (From Ioannidis JP, Lau J. State of the evidence: current status and prospects of metaanalysis in infectious diseases. Clin Infect Dis 1999;29:117885)

Figure 5:. A) Symmetrical funnel plot. B) Asymmetrical funnel plot, the small negative studies in the bottom left corner is missing