What is the Cochrane Collaboration?
What is a systematic review?
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Archie Cochrane (1909-1988)
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“It is surely a great criticism
of our profession that we
have not organised a
critical summary, by
specialty or subspecialty,
adapted periodically, of all
relevant randomized
controlled trials”.
Archie Cochrane, 1979
Collaboration’s Mission Statement
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The Cochrane Collaboration is a unique
worldwide organization that aims to help people make well informed decisions about health care by preparing, maintaining and
promoting the accessibility of systematic reviews of the effects of health care
interventions.
www.cochrane.org
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Centres
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Networks
Methods Groups
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Fields
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Steering Group
Structure of
The Cochrane Collaboration
Review Groups
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Cochrane Centres
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Cochrane Review Groups
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• International group of experts with an
interest in a health problem area
• Prepare and maintain systematic reviews
• Willing and able to review all relevant
research on health care problems related to
their area
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• Back
• Effective Practice and Organization of Care
• Hypertension
• Inflammatory Bowel Disease and Functional Bowel Disorders
• Musculoskeletal
• Upper Gastrointestinal and Pancreatic Diseases
Cochrane Review Groups
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Worldwide there are 52 registered review groups,6 of which have their editorial base in Canada
10 Key Principles….guide the work of Cochranites
1. Collaboration …good communication, open decision-making and teamwork.
2. Building on the enthusiasm of individuals …involving and supporting people based on interest and including consumers.
10 Key Principles (cont)3. Avoiding duplication …maximise efficiency, one
review is enough.
4. Minimising bias …scientific rigour, broad participation, and avoiding conflicts of interest.
5. Keeping up-to-date …up-dating reviews by identifying and adding new trials at least every 2 years.
10 Key Principles (cont)6. Ensuring relevance …choosing outcomes that matter
to patients.
7. Ensuring access …wide dissemination ...appropriate price, content and medium to meet needs of users worldwide.
8. Quality improvement …improving methodology, encouraging feedback and criticism and responding to it.
10 Key Principles (cont)9. Ensuring continuity …responsibility for reviews,
editing, and key functions is maintained and renewed.
10. Enabling wide participation …announced at the 8th Colloquium 2000 in Cape Town, South Africa
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www.thecochranelibrary.com
New Editor-in-Chief: Dr. David Tovey
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What is The Cochrane Library?
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- Main output of
Cochrane Collaboration
- Contains Cochrane
reviews & other
databases
www.thecochranelibrary.com
Cochrane Library
2016
6744 systematic reviews
2439 protocols (reviews in preparation)
>12,000 abstracts of non-Cochrane systematic reviews
> 750,000 controlled clinical trials
Excellent search engine.
The Cochrane Library Search takes place every second
Abstract is viewed every 2 seconds
Full text review is downloaded every 3 seconds.
2014 Impact Factor 6.035
2014 Hypertension Group impact factor 7.571
Systematic Review Definition: A concise summary of the best available
evidence that addresses a sharply defined clinical
question and attempts to answer it using explicit and
rigorous methods to identify, critically appraise and
synthesize all relevant studies.
Only uses scientifically valid evidence. Evidence-based is synonymous with scientifically valid.
Thomas C Chalmers (1917-
1995)
Thomas C Chalmers Outspoken advocate for “randomized controlled trials”.
“Randomize the first patient”
“In the absence of good evidence it is unethical to treat
patients with an unproven intervention except in a
randomised clinical trial comparing the new
intervention with standard therapy.”
Why are randomised
controlled trials
necessary?
Paradigm (mind-set) for decision to
administer or take an intervention
In the absence of good evidence (science), give an
intervention only as part of an RCT.
Otherwise use interventions where the benefits have
been proven to outweigh the harms in a systematic
review of RCTs.
Intervention in the absence of evidence = “snake oil”
Many health interventions are scientifically unproven
and thus no different from “snake oil”
Introduction to Cochrane
systematic reviews
Registering a Title
Use ‘PICOS’ to define the question
•Participants – Describe the specific patient population
characteristics and/or context of the condition or disease.
•Intervention – Define the intervention(s).
•Comparison – Define the control intervention.
•Outcome – Define the outcomes of interest from the most
important to the least
•Study Design – Define the type of study that is acceptable
to answer this question (usually RCTs).
Exercise Your Uncle (age 70) is concerned that he is at risk of
becoming demented as both his parents developed
dementia in their 70’s.
He read in the paper that statins may reduce the risk of
developing dementia and he is asking you if he should
take a statin.
Why would taking a statin reduce the risk of
developing dementia?
Create a systematic
review question (PICOS)
for this review.
PICOS Population Healthy adults
Intervention Statin
Control Placebo
Outcome Dementia
Study design RCT of > 1 year duration.
Cochrane Library
Statins for the Prevention of Dementia
January 2016
Review details Vascular risk factors including high cholesterol levels
increase the risk of vascular dementia or Alzheimer's disease. Observational studies have suggested an association between statin use and lowered incidence of dementia.
Results: 2 trials with 26,340 participants aged 40 to 82 years of whom 11,610 were aged 70 or older.
Incidence of dementia: odds ratio (OR) 1.00, [0.61 to 1.65]
No differences between statin and placebo groups on five different cognitive tests.
Clinical answer Advise your uncle that there is reasonable evidence
that taking a statin will have no effect on his risk of
dementia.
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Advantages of a Cochrane review
Rigour of methodology
Broad scope of literature included
Updated and maintained
Inclusiveness of perspectives
Plain language summary
Independence from commercial interests
Risk of bias is estimated and included in the interpretation of the evidence
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Steps in doing Systematic
Review Identifying a question (PICOS)
Registering the Title
Writing the protocol
Search to find all trials (Cochrane Library etc)
Choosing and entering relevant trials
Characteristics of included and excluded trials
Steps in doing Systematic
Review (cont) Risk of bias of included trials
Extracting and entering data
Interpreting findings (subgroup analysis, sensitivity
analysis)
Writing results and discussion
Summary of Findings Table, conclusions and abstract
Submit review for publication
Risk of Bias tool Sequence generation (randomization)
Allocation concealment
Blinding (participants, investigators, outcomes)
Incomplete outcome data
Selective reporting
Other biases
Proper randomization reduces the risk of imbalance in known and
unknown important prognostic factors which could influence the course of the process under evaluation.
Allocation concealment Inadequate or unclear concealment of allocation
produces effect estimates that exaggerate the true effect by 29%.
Blinding
Trials with inadequate blinding produce
effect estimates that on average exaggerate
the effect by 14% (Egger 2003) to 17%
(Schultz 1995).
Incomplete outcome data Data must be reported according to the intention to
treat principle.
Loss to follow-up potentially invalidates the results.
It is common that adverse effects are incompletely
reported.
Selective reporting bias Multiple scales in a trial are measured and the only
ones reported are those that achieve statistically
significant positive effects.
Other biases Publication bias
Patient selection bias (limited to patients known to
respond to or tolerate the intervention).
Early termination of trial bias.
Sponsor bias.
Life is full of trials.
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What have I learned
from the Cochrane
Collaboration?
Is the Cochrane Library useful
for you? When you were 18 after a minor basketball injury you
developed a swollen painful right leg.
You went to the emergency and were found to have a
deep venous thrombosis.
You were treated with anticoagulants for a short time
and are now fine.
Next week you are booked on a trip to Hong Kong.
Is there anything you should do?
Compression stockings for preventing deep vein thrombosis in
airline passengers.
A Cochrane Systematic
Review
Compression stockings for preventing deep vein thrombosis
in airline passengers
Air travel might increase the risk of deep vein thrombosis (DVT). It
has been suggested that wearing compression stockings might
reduce this risk.
Objectives
To assess the effects of wearing compression stockings versus not
wearing them among people travelling on flights lasting at least four
hours.
Search methods
The Cochrane Peripheral Vascular Diseases Group searched their
Specialized Register (last searched April 2007) and the Cochrane
Central Register of Controlled Trials (CENTRAL) in The Cochrane
Library (inception to Issue 1, 2007). The authors searched
MEDLINE (January 1966 to November 2005), EMBASE (January
1980 to December 2005) and several other electronic or grey
literature sources, detailed in full in the review.
Selection criteria
Randomized trials of compression stockings versus no stockings in
passengers on flights lasting at least four hours. Trials in which
passengers wore a stocking on one leg but not the other, or those
comparing stockings and another intervention were also eligible.
Data collection and analysis
At least two authors independently assessed the quality of each study
and extracted data. We sought additional information from trialists.
Main results
Ten randomized trials (n = 2856) were included; nine (n = 2821)
compared wearing stockings on both legs versus not wearing them, and
one (n = 35) compared wearing a stocking on one leg for the outbound
flight and on the other leg on the return flight. Of the nine trials, seven
included people judged to be at low or medium risk (n = 1548) and two
included high risk participants (n = 1273). All flights lasted at least seven
hours.
Main results (cont)
Fifty of 2637 participants with follow-up data available in the trials
of wearing stockings on both legs had a symptomless DVT; three
wore stockings, 47 did not (odds ratio 0.10, 95% confidence
interval 0.04 to 0.25, P < 0.00001). There were no symptomless
DVTs in three trials. No deaths, pulmonary emboli or symptomatic
DVTs were reported. Wearing stockings had a significant impact
in reducing oedema (based on six trials). No significant adverse
effects were reported.
Authors' conclusions
Airline passengers similar to those in this review can expect a
substantial reduction in the incidence of symptomless DVT and
leg oedema if they wear compression stockings. We cannot
assess the effect of wearing stockings on death, pulmonary
embolus or symptomatic DVT because no such events occurred
in these trials. Randomized trials to assess these outcomes
would need to include a very large number of people.
Exercise Search the Cochrane Library to find out whether
ACE inhibitors or ARBs are better for treating patients with hypertension.