This document outlines a meta-analysis presentation by Dr. Adrian V. Hernandez, covering the definition, objectives, types, and methodology of meta-analysis, including the importance of study selection and biases. It discusses critical issues such as heterogeneity, publication bias, and the generation of hypotheses, along with reporting guidelines like PRISMA and MOOSE. The presentation emphasizes the value of meta-analyses in synthesizing research findings, enhancing precision, and supporting regulatory processes.

1. Meta-analysis
Adrian V. Hernandez, M.D., Ph.D.
Assistant Professor of Medicine
Quantitative Health Sciences
October 21, 2010

2. OUTLINE
FIRST PART (40 minutes)
Introduction, objectives, types of meta-analysis, definition
of research question, getting information,
inclusion/exclusion criteria
Break 10 minutes
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3. OUTLINE (2)
SECOND PART: 50 MINUTES
• Analysis (models, methods, heterogeneity, publication
bias, quality, subgroup analysis)
• Reporting of meta-analysis (PRISMA, MOOSE guidelines)
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4. META-ANALYSIS: FACTS
• Too much information is available
• Many meta-analyses published lately:
1989-1993: 1301 1994-1998: 2532
1999-2003: 4917 2004-2008: 10567
• Why meta-analyses?
Saves money and effort
Evaluates limitations of the evidence
Designs future research
Provides evidence for regulatory processes
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5. OBJECTIVES
• Summarize and integrate results of studies
• Analyze differences among studies
• Overcome small sample sizes
• Increase precision of effects
• Evaluate effects in subsets of patients
• Generate new hypotheses
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6. TYPES OF META-ANALYSES
• Randomized controlled trials (RCTs)
• Observational Studies
• Diagnostic studies
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7. CRITICAL ISSUES
• Identification and selection of studies
• Heterogeneity of results
• Analysis of data
• Reporting of results
• Interpretation of published results
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8. IDENTIFICATION AND SELECTION
OF STUDIES
• The most critical step of a meta-analysis
• Clearly specified in protocol
• Phases: 1. Definition of research question
2. Literature search
3. Choice of relevant studies
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9. DEFINITION OF RESEARCH QUESTION
• Are the beneficial and harmful effects of
glycoprotein IIb/IIIa receptor blockers similar between
younger and older NSTE-ACS patients?
• What is the risk of HF with the use of rosiglitazone
and pioglitazone in patients at high risk of DM and
with type 2 DM?
• Which are the risk factors associated with
hypercapnia in obese patients with OSA and without
COPD?
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10. LITERATURE SEARCH
• Pubmed-Medline (www.pubmed.gov)
• Embase (www.embase.com)
• Ovid-Medline (www.ovid.com)
• The Web of Science (isiknowledge.com)
• Cochrane Library (www.cochrane.org)
• Scopus (www.scopus.com)
• Google Scholar (scholar.google.com)
More on: Steinbrook R. NEJM 2006; 354:4-7.
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11. LITERATURE SEARCH - BIASES
• Publication bias
• Search bias
• Selection bias
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12. PUBLICATION BIAS
Positive results are more likely to be published than
negative results
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13. PUBLICATION BIAS (2)
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14. PUBLICATION BIAS (3)
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15. PUBLICATION BIAS (4)
How to avoid/diminish?
• Identify unpublished studies (e.g. Nissen SE et al. NEJM 2007)
• Search registries (e.g. NIH’s http://clinicaltrials.gov)
• Do not discard studies in other languages (e.g. German,
French, Spanish)
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16. SEARCH BIAS
How happens? Limited number of search engines
Inappropriate keywords
How to avoid/diminish?
• At least 3 search engines
• Use relevant keywords and show them (e.g. for RCTs:
see Dickersin K et al. BMJ 1994; 309: 1286-91)
• Two or more researchers
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17. SELECTION BIAS
How happens? Long list of potential articles
Selection necessary (similarity, -replication)
How to avoid/diminish?
• Define clear list of inclusion and exclusion criteria
• Two or more researchers
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18. INCLUSION/EXCLUSION CRITERIA
• Objective
• Population studied
• Study design-Quality of data
• Sample size
• Treatment/Intervention
• Controls
• Duration of study
• Calendar time
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19. J Gastrointest Surg (2009) 13:649–656
DOI 10.1007/s11605-008-0756-8
Inclusion: phase III RCTs, Gum chewing vs. control
(active/placebo) on time to flatus/LOS, elective colorectal
surgery for localized disease (cancer or not), open or
laparoscopic, >15 years, English, 1960-2008.
Exclusion: Non-randomized studies, surgery beyond
colorectal, prior colonic surgery, emergency surgery.
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20. COMBINATION OF STUDIES ALWAYS
POSSIBLE?
Enough info?, quality?, heterogeneity?
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21. AVAILABILITY OF INFORMATION
Summary effects only (OR, RR, HR, mean [SD]). Most of
the cases → Limited analyses.
What to do? Contact authors, Patient level data
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22. ALL STUDIES CAN BE COMBINED?
Only reasonably well conducted RCTs?
Observational studies also?
Similar results between RCTs and observational?
Similar results overtime?
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23. MA OF RCTs vs. OBSERVATIONAL
• 3 RCTs, n=10731 diabetic/high risk of diabetes,
>12 months f-up: OR 2.1 (95% CI: 1.1-4.1)
• 4 Retrospective cohorts, n=67382 diabetic
patients: OR 1.6 (95% CI 1.3-1.8)
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24. MAs OVERTIME: OBSERVATIONAL (1)
17 studies (3C, 14CC)
RR for ischemic stroke: 2.8 (95%CI 2.2-3.4)
Cohorts: 3.2 (2.0-5.3)
Case-control: 2.8 (2.2-3.5)
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25. MAs OVERTIME: OBSERVATIONAL (2)
20 studies (4C, 16CC)
RR for all-stroke: 1.9 (95%CI 1.4-2.6)
Cohorts: 1.0 (0.5-1.8)
Case-control: 2.1 (1.6-2.9)
RR for ischemic stroke: 2.7 (95%CI 2.2-3.4)
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