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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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AUSTRALASIAN COCHRANE CENTRE
To Cochrane or not: that's the question
1
Professor Hesham Al-InanyEditor, 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?
4
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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 acupunctureimprove pregnancy outcomes ?
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7RCT : Gold standard
Participants
R a
n d
o m
l
y A
s s
i g
n e d
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: SteffComparison: 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 acupunctureimprove pregnancy outcomes ?
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2. Inclusion and exclusion criteria pre-statedParticipants 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 rateAdverse 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 entryDisagreements 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: SteffComparison: 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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com
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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 tellyou what the comparisonis and what the outcomeof interest is
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At the bottom there’sa horizontal line. This is the scale measuringthe treatment effect.
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The vertical line in themiddle is where thetreatment and control have the same effect – there is no differencebetween the two
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For each study there is an id
The data foreach trial are here, divided into the experimental and control groups
This is the % weightgiven to thisstudy 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 shapewhere 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
searchesinclusions
qualitydata extraction
meta-analysis
editorial + external review
outside comments and criticismsnew 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.