Meta Analysis

What is meta analysis?
Quantitative approach for

systematically combining results of
previous research to arrive at
conclusions about the body of research.
What does it mean?

Quantitative : numbers
Systematic : methodical
combining: putting together
previous research: what's already done
conclusions: new knowledge
The popularity of meta

analyses
publications
3000
Number of Publications
2500
2000
1500
1000
500
0
93-94
94-95
95-96
96-97
97-98
98-99
99-00
2000-1
2001-2
2002-3
2003-4
Year of Publications
Number of Meta Analysis publications are steadily increasing

since 1993. We graphed the counts of journal articles included
meta analysis as publication type from Pubmed, from years
Four Steps of Meta

Analysis
Identify your studies
Determine eligibility of studies
Inclusion: which ones to keep
Exclusion: which ones to throw
out
Abstract Data from the studies

Analyze data in the studies
statistically
Identify your studies

Be methodical: plan first
List of popular databases to search
Pubmed/Medline
Embase
Cochrane Review/Trials Register
Other strategies you may adopt

Hand search (go to the library...)
Personal references, and emails
web, eg. Google (
http://scholar.google.com)
How to Search for

literature
Formulate your question appropriately
If you are searching pubmed
Use Medical Subject Headings (MeSH) [1]
Lookup word in text word, abstract, title
[2]
Combine [1] with [2] using boolean logic
Set up proper filters
For Others, use text word, abstract

Huh?!, what is boolean logic??
Boolean Logic: AND
this is AND zone, covering common area

between two ellipses
Boolean Logic OR
this is boolean OR, covering the two ellipses
Example: Research Issue

Let's say we want to know whether
streptokinase is protective for death
from acute myocardial infarction.
How should we set up a search
strategy? We will search pubmed
only
The Search
streptokinase[text word] OR acute myocardial
infarction[text word] produces ALL articles
that contain EITHER streptokinase OR acute
myocardial infarction anywhere in the text
inclusive, many
streptokinase [text word] AND acute
myocardial infarction [text word] will capture
only those subsets that have BOTH
streptokinase AND acute myocardial infarction
anywhere in the text restrictive, few.......
Next, we shall look at the PUBMED Screen
Remember to choose both PUBMED,

Choose your DATABASE hereand MESH for formulating search.
Choose PUBMED CENTRAL for free
articles!
Keep some, throw out

others
Cannot include all studies
Keep the ones with
high levels of evidence
good quality
check with QUOROM guidelines
Usually, MA done with RCTs

Case series, and case reports definitely out
Selection problems are major problems
MA = Meta Analysis; RCT = Randomized Controlled Trial
Plan of Action
ARE THE STUDIES ELIGIBLE FOR MA (STEP I)?
DISCARD
NO
YES
ABSTRACT THE DATA

ENTER INTO A SPECIFIED FORMAT
How to Abstract Data:

Guidelines
Create a spreadsheet (Excel, or Open Office
Calc)
For each study, create the following columns:

name of the study
name of the author, year published
number of participants who received intervention
number of participants who were in control arm
number who developed outcomes in intervention
number who developed outcomes in control arm
Lets do that to our streptokinase myocardial

infarction study, next
Spreadsheet Data for Strepto Study

We got like 22 studies to do our meta analysis, after all
Cont
We created seven columns
trial:
trial identity code
Trial name: name of trial
year:
year of the study
pop1:
study population
deaths1:
deaths in study
pop0:
control population
deaths0:
deaths in control
Analyze Data
Statistically
Combine data to arrive at a summary, 3
measures
Effect Size (Odds Ratio)
Variance with 95% Confidence Interval
Test of heterogeneity
Two Graphs
Forest Plot
Funnel Plot
Examine why the studies are

heterogeneous, if they are
Use Statistical Packages, several choices
Lets see what we got for streptokinase
versus deaths from AMI
Summary Estimates for Strepto

Study
Mantel Haenszel OR=0.77
95% Confidence Interval

[0.72, 0.83]
Test of Heterogeneity:
Chi-square (df=21) = 31.5
P-Value = 0.07
The pooled Odds Ratio

shows that those
receiving streptokinase
at AMI are about 77% at
risk of death (23% less
That in 95 out of 100
likely to die)
such meta analyses, the
pooled Odds Ratio would
lie between 0.72 and
0.83, indicating a
statistically significant
protective effect
That these studies
were not
significantly
heterogeneous
Funnel Plot: what and

how to read
Cont..
Plots the effect size against the sample size
of the study
To study a funnel plot, look at its LOWER
LEFT corner, thats where negative or null
studies are located
If EMPTY, this indicates PUBLICATION BIAS
Note that here, the plot fits in a funnel, and
that the left corner is not all that empty, but
we cannot rule out publication bias
Issues in meta analysis

Choosing a model
Fixed effects model or random effects?
Bias in meta analysis

poor quality of trials
publication bias
Quality control in meta analysis

QUOROM guidelines
Statistical Software for meta

analysis
Fixed Effects or Random Effects

Model?
Fixed Effects Model
Effects Model
Random
conduct if it is reasonable to
Conduct if test of heterogeneity is
assume underlying Rx effect is
significant (shows heterogeneity)
SAME for all studies
Pooling: Mantel Haenszel OR
Assume that TRUE log Assume that
TRUE log normal distribution
Test: test of heterogeneity
If significant, go for random
Method: DerSimonian
effects model
Lairs method (DSL) of
short 95% CI for summary
calculating Odds Ratio
smaller summary estimate
OR=0.78 [0.69,0.88]
OR=0.77 [0.72,0.83]
Bias in Metaanalysis
Poor Quality of Trials
To avoid them, learn more at CONSORT statement
[http://www.consort-statement.org ]
Publication Bias
study showing beneficial effects of new treatment
more likely to be published than one showing no
effect
negative trials assumed to contribute less; never
show up in the literature base
use several approaches to avoid this
Use Funnel Plots to examine the influence of
publication bias
Quality Control in MA:QUOROM

Table
Detailed Guidelines
A Good Checklist
Use it for reporting
Meta Analysis
Systematic
reviews
Statistical Software for Meta

Analysis
Huge Checklist
[http://faculty.ucmerced.edu/wshadish/]
Free Software:
EpiMeta: from Epi Info
Revman: from Cochrane Collaboration
meta package in R for statistical
computing
Non-free
meta module in STATA
Summarizing...
Defined meta analysis
quantitative research synthesis
Outlined basic steps

Information retrieval
Data Abstraction
Data Analysis
Model Selection: Fixed Effects or
Random effects
Outlined some issues and listed

software

Meta Analysis

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What are the four steps of a meta-analysis?

What are the four steps of a meta-analysis?

What are some potential sources of bias in meta-analyses?

What are some potential sources of bias in meta-analyses?

What is meta analysis?

Quantitative approach for

What does it mean?

The popularity of meta

Number of Meta Analysis publications are steadily increasing

Four Steps of Meta

Abstract Data from the studies

Identify your studies

Other strategies you may adopt

How to Search for

For Others, use text word, abstract

Boolean Logic: AND

this is AND zone, covering common area

this is boolean OR, covering the two ellipses

Example: Research Issue

Remember to choose both PUBMED,

Keep some, throw out

Usually, MA done with RCTs

MA = Meta Analysis; RCT = Randomized Controlled Trial

ABSTRACT THE DATA

How to Abstract Data:

For each study, create the following columns:

Lets do that to our streptokinase myocardial

Spreadsheet Data for Strepto Study

Examine why the studies are

Summary Estimates for Strepto

95% Confidence Interval

The pooled Odds Ratio

Funnel Plot: what and

Issues in meta analysis

Bias in meta analysis

Quality control in meta analysis

Statistical Software for meta

Fixed Effects or Random Effects

Quality Control in MA:QUOROM

Statistical Software for Meta

Outlined basic steps

Outlined some issues and listed

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