first part.ma.oct202010
TRANSCRIPT
Meta-analysis
Adrian V. Hernandez, M.D., Ph.D.Assistant Professor of Medicine
Quantitative Health Sciences
October 21, 2010
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FIRST PART (40 minutes)
Introduction, objectives, types of meta-analysis, definition of research question, getting information, inclusion/exclusion criteria
Break 10 minutes
OUTLINE
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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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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 effortEvaluates limitations of the evidenceDesigns future researchProvides evidence for regulatory processes
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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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TYPES OF META-ANALYSES
• Randomized controlled trials (RCTs)
• Observational Studies
• Diagnostic studies
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CRITICAL ISSUES
• Identification and selection of studies
• Heterogeneity of results
• Analysis of data
• Reporting of results
• Interpretation of published results
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IDENTIFICATION AND SELECTIONOF 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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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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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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LITERATURE SEARCH - BIASES
• Publication bias
• Search bias
• Selection bias
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PUBLICATION BIAS
Positive results are more likely to be published than negative results
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PUBLICATION BIAS (2)
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PUBLICATION BIAS (3)
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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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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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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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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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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.
J Gastrointest Surg (2009) 13:649–656DOI 10.1007/s11605-008-0756-8
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COMBINATION OF STUDIES ALWAYS POSSIBLE?
Enough info?, quality?, heterogeneity?
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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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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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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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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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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)