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  • Define systematic review and meta-analysis

  • Describe the framework and process of systematic review

  • Understand the analytical framework for conducting a meta-analysis

  • Interpret results of a meta-analysis

  • Understand heterogeneity and bias in meta-analysis

  • Understand the role of systematic review in research and practice



  • Forest plots

  • Funnel plots


  • Heterogeneity

  • Meta-analysis




  • Publication bias

  • Robis

  • Systematic review


On May 21, 2007, the New England Journal of Medicine (NEJM) published a systematic review and meta-analysis on the risk of myocardial infarction and death from cardiovascular causes with rosiglitazone (Avandia®), a medication used to treat patients with type II diabetes mellitus.1 The review found rosiglitazone to be associated with increased risk of myocardial infarction, and a borderline increase in risk of death from cardiovascular causes. On the same day, the US Food and Drug Administration (FDA) issued a safety alert on rosiglitazone, and this was upgraded to a black box warning for heart-related risks later in 2007. This resulted in further clinical research and replication of findings from meta-analysis. In September 2010, the FDA took further action and significantly restricted access to rosiglitazone to only patients with type II diabetes who cannot control their diabetes on other medications. The drug was withdrawn entirely from the market in European countries and New Zealand. The systematic review and meta-analysis published in NEJM led to the decline of rosiglitazone, a drug that captured $3.3 billion in US sales in 2006.2 While controversial, the case of rosiglitazone is one example of how systematic review and meta-analysis can be helpful in understanding the risks and benefits of medications when evidence provided by existing studies is inconclusive or conflicting.

This chapter is divided into two sections. The first section describes the elements of the systematic review process. The second section describes meta-analysis as a method to quantitatively synthesize evidence from studies identified in a systematic review.

Systematic review is a structured process for identifying and summarizing existing studies that address a specific question. Systematic reviews help patients, healthcare providers, and policy makers understand evidence and formulate best practices.3 This is especially important given the volume of literature and common challenges that exist in interpreting inconsistent results. Systematic review is especially useful when multiple strong studies are available, but the answers provided by these studies are not in perfect agreement. Systematic review is not useful when there is so much agreement among available studies that the question is already answered, or when too few studies exist so that the question can be answered by review and critique of individual studies. A systematic review should always include a synthesis of included studies, but this synthesis can be qualitative or quantitative. Quantitative syntheses are typically in the form of meta-analysis.

Meta-analysis is the quantitative synthesis of data ...

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