the role of Cochrane collaboration and specifically the menstrual disorder & subfertility group is illustrated . simple explanation how to use cochrane reviews is done.

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To Cochrane or not:
that's the question
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Professor Hesham Al-Inany
Editor, Cochrane Menstrual Disorders & Subfertility
Group
Editor, British Journal of Obstetrics & gynecology
Cairo University
Egypt

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Preparing, maintaining and disseminating systematic
reviews of the effects of health care
THE COCHRANE COLLABORATION

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Antenatal corticosteroids for preterm
birth
• Survey:
• 1980 RCOG survey: 42%
• 1984 Belgium : 32%
• 1990 UK centers : 58%
• 1992 US Obs: 8-34%
• NIH :
•”corticosteroid Rx is indicated for women at risk of
premature delivery ………..
and will result in a substantial decrease in neonatal
morbidity and mortality as well as substantial savings”

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Learning objectives
 Why are systematic reviews important?
 Why Cochrane systematic reviews?
 How to join for a Cochrane systematic review?
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How do we treat our patients?
 Using evidence from high quality research to
answer specific questions

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For example:
In women with infertility does acupuncture
improve pregnancy outcomes ?

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RCT : Gold standard
Participants
RandomlyAssigned
Intervention Group
Control Group
Follow-up
Follow-up
Intervention Group
Control Group

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But there are many RCTs on this topic
 Some with conflicting results
 Some with small number of participants

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Why are systematic
reviews useful?

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Systematic review
 Uses tools to summarise the results of a number
of trials/studies
 Systematic and scientific methodology
 Helpful in clinical decision making

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Advantages
• To increase power, Many individual studies
are too small to detect small effects, but when
several are combined there is a higher chance of
detecting an effect.
• To improve precision: The estimation of an
intervention effect can be improved when it is
based on more data.

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Review : Steff
Comparison: 01 Absence of evidence and Evidence of absence
Outcome: 01 Increasing the amount of data...
Study Treatment Control OR (fixed) OR (fixed)
or sub-category n/N n/N 95% CI 95% CI
1 study 10/100 15/100 0.63 [0.27, 1.48]
2 studies 20/200 30/200 0.63 [0.34, 1.15]
3 studies 30/300 45/300 0.63 [0.38, 1.03]
4 studies 40/400 60/400 0.63 [0.41, 0.96]
5 studies 50/500 75/500 0.63 [0.43, 0.92]
0.1 0.2 0.5 1 2 5 10
Favours treatment Favours control
In the example below, as more data is included,
the overall odds ratio remains the same but the
confidence interval decreases.
It is not true that there is ‘no difference’ shown in
the first rows of the plot – there just isn’t enough
power to show a statistically significant result.

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1. Clear objectives stated with a well formulated
clinical question
2. Inclusion and exclusion criteria stated
3. Comprehensive search strategy
4. Systematic approach with all relevant studies
5. Excluded studies listed with reasons
6. Trial results are pooled if possible (meta-analysis)
Features not in narrative reviews

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1. Clearly stated objective with clinical
question
Participants Intervention Comparison Outcome
In women with infertility does acupuncture
improve pregnancy outcomes ?

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2. Inclusion and exclusion criteria pre-stated
Participants Intervention Comparison Outcome
In women with infertility does acupuncture treatment
improve pregnancy outcomes ?
• Women <45 yo
• Infertility for > 1 yr
• No other Rx or
ART?
Acupunture Live birth rate
Adverse events
Sham
Acupuncture
or
no treatment

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3. Comprehensive search for all
studies
All databases are searched to avoid
publication bias? MEDLINE, EMBASE,
CINHAL and others

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Publication Bias
 Research with statistically significant
results is more likely to be submitted for
publication and more likely to be
published.

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Advanced ovarian cancer
Comparison: combination chemotherapy versus
single chemotherapy
Published trials
0.7 1 1.3
Registered trials
Simes 1987
Outcome: mortality

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Not restricted to English language

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4. Systematic approach
Independent tasks by 2 or more reviewers:
 Selection of studies for inclusion and
tabulated
 Data extraction
 Quality assessment
 Data entry
Disagreements resolved by 3rd party

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5. Excluded studies listed
 All excluded studies included in a table
 Reasons given for exclusion
 Transparency minimises bias

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6. Pooling of results using meta-analysis
if appropriate and possible
What is a meta-analysis?
 A statistical tool to combine results of
studies
 Using Revman software (free to
download)
 Valuable way to display a summary of
the trials

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Why do we need it
 To avoid Type II error: Investigators did
not detect a difference when a
difference actually exists

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Review : Steff
Comparison: 01 Absence of evidence and Evidence of absence
Outcome: 01 Increasing the amount of data...
Study Treatment Control OR (fixed) OR (fixed)
or sub-category n/N n/N 95% CI 95% CI
1 study 10/100 15/100 0.63 [0.27, 1.48]
2 studies 20/200 30/200 0.63 [0.34, 1.15]
3 studies 30/300 45/300 0.63 [0.38, 1.03]
4 studies 40/400 60/400 0.63 [0.41, 0.96]
5 studies 50/500 75/500 0.63 [0.43, 0.92]
0.1 0.2 0.5 1 2 5 10
Favours treatment Favours control

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Graphic
Display:
ß blockers in
secondary
prevention after
myocardial
infarction.

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Cumulative Meta-analysis

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Meta-analysis vs. a “Mega-study”
Single large studies are liable to:
 Long duration
 Huge funding
a drug that reduces mortality by 10% from myocardial
infarction may need a study including 10.000 patients

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 Why are systematic reviews important?
 Why Cochrane systematic reviews?
 How to prepare a protocol for a Cochrane
systematic review
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Advantages of Cochrane reviews
 Updating of reviews regularly
 Methodologically robust
 Less likely to be biased

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How do (Cochrane) systematic reviews
reduce bias?
 Prestated methods published
 Limit publication bias (very comprehensive
search)
 Limit commercial and industry sponsorship
of reviews

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Studies with funding bias are more likely to have
favourable results (Lundh et al 2012)
 Add reviews on this topic

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“..we observed far superior
reporting standards of Cochrane
reviews compared to non-
Cochrane therapeutic ones.”
“For therapeutic reviews, all the
Cochrane ones reported assessing
the quality of included studies
whereas only half of the non-
Cochrane did.”
“The seven industry supported
reviews that had conclusions
recommended the
experimental drug without
reservations, compared with
none of the Cochrane reviews,
although the estimated
treatment effect was similar on
average
Better quality reviews

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Our structure
• more than 27,000 people in over 100 countries
 almost all volunteers
• decentralised structure
 52 Cochrane Review Groups (CRGs)
• specific areas of health care
• first point of contact for authors
• international and multidisciplinary
• largely funded by government grants

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Cochrane centers all over the world

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COCHRANE CENTREwww.thecochranelibrary.

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Cochrane Reviews
Randomised
controlled trials
Methodology
papers

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Displaying results graphically
 Revman software produces forest plots

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there’s a label to tell
you what the comparison
is and what the outcome
of interest is

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At the bottom there’s
a horizontal line. This
is the scale measuring
the treatment effect.

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The vertical line in the
middle is where the
treatment and control
have the same effect –
there is no difference
between the two

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For each study
there is an id
The data for
each trial
are here, divided
into the experimental
and control groups
This is the % weight
given to this
study in the
pooled analysis

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•Each study is given a blob, placed where the data measure the effect.
•The size of the blob is proportional to the % weight
•The horizontal line is called a confidence interval and is a measure of
how we think the result of this study might vary with the play of chance.
•The wider the horizontal line is, the less confident we are of the
observed effect.
The label above the graph
tells you what statistic
has been used
The data shown in
the graph are also
given numerically

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The pooled analysis is given a diamond shape
where the widest bit in the middle
is located at the calculated
best guess (point estimate),
and the horizontal width is the
confidence interval
Definition of a 95% confidence interval: If a trial was repeated 100 times,
then 95 out of those 100 times, the best guess (point estimate) would lie
within this interval.

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Reading the graphs
What
outcome?
What
measure of
effect size?
The
events
The
pooled
ORs
And confidence
intervals
weighting?

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Reading the graphs
What
measure of
effect size?
And confidence
intervals
The
pooled
ORs
Heterogeneity
The
events

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Limitations ???
 Takes long time to publish and huge
effort to be done
 Authors may lose interest in updating SR
 Not considered for PhD as main
research (reviewer not author ??)
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Practical tips for new comers
 no specific criteria to be an author
 Determine which field of interest
 Choose a very specific point
 formulate a question
 make a quick search for RCTs
 preferably not more than 6 RCTs

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The life cycle of a Cochrane review
Title
(registered)
Prepare
Protocol
Register
Protocol
Systematic Review
Review online
Time Frame
6 Months
12 Months
Lifelong
editorial + external review
searches
inclusions
quality
data extraction
meta-analysis
editorial + external review
outside comments
and criticisms
new data
2 or more
reviewers

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What support is available?
 an on-line systematic review training
programmes can be accessed at:
 http://www.cochrane-net.org/openlearning
 http://www.cochrane.org/training/authors

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The end.....
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http://www.cochrane.org/about-us
/newcomers-guide.