Transcript Cochrane Review

University of Ferrara
Ilaria Casetta, MD
Neurological
Clinic
Copyright © The Cochrane Collaboration
BRIEF HISTORY

The Cochrane
Collaboration is named in
honour of Archie
Cochrane, a British
medical researcher who
contributed greatly to the
development of
epidemiology as a
science.
Professor Archibald Leman Cochrane, CBE FRCP FFCM, (1909 - 1988)
Cardiff University Library, Cochrane Archive, University Hospital Llandough.
Background
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Healthcare decision-making needs to be
informed by high quality, timely research
evidence
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Prof. Cochrane stressed the importance of
using evidence from randomised controlled trials
(RCT's) because these were likely to provide
much more reliable information than other
sources of evidence.
Background
"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 randomised controlled trials."
(1979)
Why do we need critical
summaries?
Most doctors do not have the time to
critically read all original papers
 Often the results of available trials are not
consistent
 Textbooks become quickly out of date
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Background and aims
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Established as an international organisation in
1993, registered as a charity in the U.K.
Aim- To help people make well-informed
decisions about health care.
How - by preparing, disseminating and
maintaining,systematic reviews of the effects of
healthcare interventions across all areas of
health care.
Cochrane Collaboration
More than 28,000 dedicated people from
over 100 countries.
 They work together to help healthcare
providers, policy-makers, patients, their
advocates and carers , make wellinformed decisions about health care
 The members of The Cochrane
Collaboration are organised into groups,
known as 'entities',
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Organization
The main work of The Cochrane
Collaboration is done by more
than fifty Cochrane Review
Groups
Methods Groups have been
established to develop and
update methodology
The work of Cochrane Groups is
facilitated in various ways by the
work of Cochrane Centres around
the world.
The consumer network help to
establish priorities and identify
outcomes relevant to patient
Activity and outputs
Training  courses
 Methodology  Handbooks
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Cochrane Handbook for Systematic Reviews of Interventions
Cochrane Handbook for Diagnostic Test Accuracy Reviews
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Software  RevMan
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Cochrane Library
www.thecochranelibrary.com
About The Cochrane Library
 The Cochrane Library is a collection of six
databases that contain different types of
high-quality, independent evidence to
inform healthcare decision-making, and a
seventh database that provides
information about groups in The Cochrane
Collaboration.
The Cochrane Library is a
collection of evidence-based
medicine databases:
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The Cochrane Database of Systematic Reviews (Cochrane
Reviews)
The Cochrane Database of Abstracts of Reviews of Effects –
DARE (Other reviews)
The Cochrane Central Register of Controlled Trials- CENTRAL
(Clinical trials)
The Cochrane Methodology Register (Methods Studies)
Health Technology Assessment Database (Technology
Assessments)
NHS Economic Evaluation Database (Economic Evaluations)
About the Collaboration
Cochrane Central Register of
Controlled Trials (CENTRAL)
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Includes details of published articles taken from bibliographic
databases (notably MEDLINE and EMBASE), and other published
and unpublished sources. CENTRAL records include the title of the
article, information on where it was published (bibliographic details)
and, in many cases, a summary of the article. They do not contain
the full text of the article.
Each Cochrane Review Group maintains and updates a collection of
controlled trials relevant to its own area of interest (handsearch)
Cochrane Methodology
Register (CMR)
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is produced by the UK Cochrane Centre, on
behalf of the Cochrane Methodology Review
Group.
A collection of paper that report on methods of
controlled trials, and of methodological studies.
Database of Abstracts of Reviews of
Effects (DARE)
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Contains abstracts of systematic reviews that have been
quality-assessed. Each abstract includes a summary of
the review together with a critical commentary about the
overall quality.
DARE complements the CDSR by quality-assessing and
summarizing reviews that have not yet been carried out
by The Cochrane Collaboration..
DARE is produced by the Centre for Reviews and
Dissemination (CRD) at the University of York, UK.
Health Technology
Assessment Database
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brings together details of completed and
ongoing health technology assessments (studies
of the medical, social, ethical, and economic
implications of healthcare interventions) from
around the world. The aim of the HTA Database
is to improve the quality and cost-effectiveness
of health care
NHS Economic Evaluation
Database
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The NHS Economic Evaluation Database
(EED) assists decision-makers by
systematically identifying economic
evaluations from around the world,
appraising their quality, and highlighting
their relative strengths and weaknesses.
Cochrane Database of
Systematic Reviews (CDSR)
Is the leading resource for systematic
reviews in health care.
 The CDSR includes all Cochrane Reviews
(and protocols) prepared by Cochrane
Review Groups in The Cochrane
Collaboration.
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Cochrane Database of
Systematic Reviews
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Each Cochrane Review is a peer-reviewed
systematic review that has been prepared
and supervised by a Cochrane Review
Group (editorial team) in The Cochrane
Collaboration according to the Cochrane
Handbook for Systematic Reviews of
Interventions or Cochrane Handbook
for Diagnostic Test Accuracy Reviews
Cochrane Reviews
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The Cochrane Reviews are prepared by authors
who register titles with one of the 53 Cochrane
Review Groups (focusing on a specific topic
area)
Co-ordinating Editor(s), and Editorial team
including a Managing Editor and Trials Search
Co-ordinator.
The Cochrane Review Groups provide authors
with methodological and editorial support to
prepare Cochrane Reviews, and manage the
editorial process, including peer review
Systematic review
“A review that is conducted according to
clearly stated, scientific research methods,
and is designed to minimize biases and
errors inherent to traditional, narrative
reviews.”
Margaliot, Zvi, Kevin C. Chung. Systematic Reviews: A Primer for Plastic Surgery Research. PRS
Journal. 120/7 (2007)
Systematic reviews
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Systematic in identification of
literature
 Explicit in statement of
objectives, materials, and
methods
 Reproducible in its
methodology and conclusions
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Scientific approach to a
review article
Criteria determined at outset
Comprehensive search for
relevant articles
Explicit methods of appraisal
and synthesis
Meta-analysis may be used to
combine data
Systematic process involving
several steps
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Formulate the question
Plan the review (a priori protocol)
Comprehensive search
Unbiased selection and abstraction process
Critical appraisal of data
Synthesis of data (may include meta-analysis)
Interpretation of results
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All steps are described explicitly in the review.
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Well formulated question
EXAMPLE
 Population
(Patient,
Problem)
 Intervention
 Comparison
 Outcomes (primary /
secondary)
 Time
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Patients with MS
Beta Interferon
Placebo
Relapse rate/ disease
progression
After 1 year/3 years
Systematic process involving
several steps
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Formulate the question
Plan the review (a priori protocol)
Comprehensive search
Unbiased selection and abstraction process
Critical appraisal of data
Synthesis of data (may include meta-analysis)
Interpretation of results
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All steps are described explicitly in the review.
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Plan the review : protocol
The Protocol is the a priori work-plan for the
eventual review. It lays out the plan in detail.
Cochrane researchers use the protocol to describe the
proposed approach for a systematic review.
It outlines:
 the question that the review authors are addressing (the
health problem and the intervention under investigation,
how benefits and harms will be measured, and the type
of appropriate study design, such as the inclusion
criteria of the studies).
 The protocol also outlines the process for identifying,
assessing, and summarizing studies in the review.
 By making this information available the protocol is a
public record, published in the CDSR
Systematic process involving
several steps
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Formulate the question
Plan the review (a priori protocol)
Comprehensive search
Unbiased selection and abstraction process
Critical appraisal of data
Synthesis of data (may include meta-analysis)
Interpretation of results
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All steps are described explicitly in the review.
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Clearly stated title and objectives
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Comprehensive strategy to search for relevant studies
(unpublished and published)
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Explicit and justified criteria for the inclusion or exclusion
of any study
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Clear presentation of characteristics of each study
included and an analysis of methodological quality
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Comprehensive list of all studies excluded and
justification for exclusion
Comprehensively search
databases to find all relevant studies
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PubMed
EMBASE
Cochrane Central Register of Controlled Trials (CENTRAL)
CINAHL
Web of Science
PsycINFO
LILACS
Databases from LMIC
Dissertation abstracts
Clinical trials registers
Handsearching of journals
Reference lists
Conference abstracts
Personal communication
Anything else you can think of.
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Database Bias – Different database can record different studies “
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Publication Bias - selective publication of articles that show positive effect
of treatment and statistical significance.
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English-language bias - occurs when reviewers exclude papers published
in languages other than English
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Citation bias - occurs when studies with significant or positive results are
referenced in other publications, compared with studies with inconclusive or
negative findings
Systematic process involving
several steps
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Formulate the question
Plan the review (a priori protocol)
Comprehensive search
Unbiased selection and abstraction process
Critical appraisal of data
Synthesis of data (may include meta-analysis)
Interpretation of results
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All steps are described explicitly in the review.
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Selection process- Refine
Search
1814
records
By excluding
 Duplicates
 Irrelevant Papers
 Studies not fulfilling
inclusion criteria
Obtaining full-text of relevant studies
7
included
Abstraction process
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Using a pre-define data abstraction form,
authors inependently abstract the data and
study characteristics from each study
determined to be eligible for inclusion.
Systematic process involving
several steps
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Formulate the question
Plan the review (a priori protocol)
Comprehensive search
Unbiased selection and abstraction process
Critical appraisal of data
Synthesis of data (may include meta-analysis)
Interpretation of results
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All steps are described explicitly in the review.
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1. Sequence generation
Assessment
Adequate sequence generation
Allocation concealment
Blinding (Patient-reported outcomes)
Blinding (Mortality)
Incomplete outcome data addressed (Short-term outcomes (2-6 wks))
Incomplete outcome data addressed (Longer-term outcomes (> 6ks))
Free of selective reporting
Free of other bias
Risk of
bias
Barry 1988
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Baylis 1989
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Cooper 1987
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Dodd 1985
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Goodwin 1986
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Sanders 1983
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(randomization)
2. Allocation concealment
3. Blinding of
participants, personnel
and outcomes
4. Incomplete outcome
data (attrition and
exclusions)
5. Selective outcome
reporting
6. Other (including topicspecific, designspecific)
Critical appraisal and assessment
of the risk of bias for each study
Systematic process involving
several steps
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Formulate the question
Plan the review (a priori protocol)
Comprehensive search
Unbiased selection and abstraction process
Critical appraisal of data
Synthesis of data (may include meta-analysis)
Interpretation of results
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All steps are described explicitly in the review.
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Synthesis of data
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“Once the data have been extracted and their
quality and validity assessed, the outcomes of
individual studies within a systematic review
may be pooled and presented as summary
outcome or effect
When data are NOT too sparse, of too low
quality or too heterogeneous
Synthesis of data when:
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Studies evaluated the
same outcomes
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Homogeneity
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Good Quality
Meta-analysis
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“Meta-analysis is a
statistical technique
for combining the
results of
independent, but
similar, studies to
obtain an overall
estimate of treatment
effect.”
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The validity of a metaanalysis depends on
the quality of the
studies included,
Meta-analysis- Forest plot
At the bottom there’s a horizontal line. This is the scale measuring the treatment effect
The vertical line in the middle is where the treatment and control have the same effect
Take care to read what the labels say – things to
the left do not always mean the treatment is better than the
control.
 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 by chance.
 The wider the horizontal line is, the less confident we are of the observed effect.
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
If the confidence interval crosses the line of no effect,
we have found no statistically significant difference in
the effects of the two interventions
Systematic process involving
several steps
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Formulate the question
Plan the review (a priori protocol)
Comprehensive search
Unbiased selection and abstraction process
Critical appraisal of data
Synthesis of data (may include meta-analysis)
Interpretation of results
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All steps are described explicitly in the review.
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Interpretation of the results
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What does it all
mean?
Implications for
patient care and
future research
The Cochrane Library
databases
The CDSR is published online monthly
(from 2010) with quarterly DVDs.Access is
free for many people in low-income and
middle-income countries via a number of
initiatives. This is in addition to general
access options, including national licenses
and subscriptions.
 Abstracts are free

The Cochrane Library usage data ,
2009
"Every day someone, somewhere searches
The Cochrane Library every second,
reads an abstract every two seconds and
downloads a full-text article every three
seconds."
Novel methodologies
To summarize evidence across reviews
 Overview of Reviews
 Network Meta-Analysis
