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Systematic reviews
What is a systematic review?
• It is a structured review integrating
pooling the results (Meta-analysis) of
individual studies addressing the same
topic.
Systematic Review
• structured : for consistent presentation of
information
• Meta-Analysis : combine and statistically
summarize the results of individual studies
Cook, D. J. et. al. Ann Intern Med 1997;126:376-380
Differences between Narrative Reviews and Systematic Reviews
QUESTION Broad Focused
SOURCES/ Usually unspecified Comprehensive;
SEARCH Possibly biased explicit
SELECTION Unspecified; biased?Criterion-based;
uniformly applied
APPRAISAL Variable Rigourous
SYNTHESIS Usually qualitative Quantitative
INFERENCE Sometimes Usually evidence-
evidence-based based
NARRATIVE SYSTEMATIC
Cook, D. J. et. al. Ann Intern Med 1997;126:376-380
Level of evidence
• I–1 Systematic reviews.
• I–2 One or more large double-blind randomised
control trials.
• II–1 One or more well-conducted cohort studies.
• II–2 One or more well-conducted case-control
studies.
• II–3 uncontrolled experiment.
• III Expert opinion.
• IV Personal experience
systematic review : why & How
Why on the Top
• Rigorous methodology
• Peer reviewed
• Relatively large sample size
• Ensures the highest quality evidence
Why do we need it
• Too much trials
• 25000 biomedical journals in print
• 8000 articles published per day
• All studies not equally well designed or
interpreted
So, we need a study of studies
• To summarize evidence from studies that
address a specific clinical question.
• to explain differences among studies on the
same question
• In a way that limit bias (rigorous methodology
& clear reporting)
Example
• Protocols in neurology units - 80% still
recommend bed rest after LP
• Systematic review of 10 trials of bed rest after
spinal puncture
– no change in headache with bed rest
– Increase in back pain
Serpell M, BMJ 1998;316:1709–10
Why do we need it
• many single trials had relatively low power
• avoid Type II error: Investigators did not
detect a difference when a difference
actually exists
• This is not surprising as the power to detect
a difference will have been increased by the
increase in the sample size
Graphic Display:
ß blockers in
secondary
prevention after
myocardial
infarction.
Why do we need it
• Systematic reviews help us to avoid the
personal bias inherent in traditional reviews
and expert opinion
Why do we need it
Example
Mitchell JRA. Timolol after myocardial infarction: an
answer or a new set of questions? BMJ 1981;282:1565-
70:
"despite claims that they reduce arrhythmias, cardiac work,
and infarct size, we still have no clear evidence that ß
blockers improve long-term survival after infarction
despite almost 20 years of clinical trials."
Cumulative Meta-analysis
Why do we need it
• Results from systematic reviews are the
cornerstone for developing practice
guidelines
systematic review : why & How
Cochrane Library
• The current resource with the highest
methodological rigor
– $235/year or abstracts only
• www.cochrane.org
• Specific point: e.g role of albumin in OHSS
Abstract
Background
Objectives
Criteria for considering studies for this review
Types of participants
Types of intervention
Types of outcome measures
Types of studies
Search strategy for identification of studies
Methods of the review
Description of the studies
Methodological qualities of included studies
Results
Discussion
Conclusions
Implications for practice
Implications for research
Internal sources of support to the review
External sources of support to the review
Potential conflict of interest
Acknowledgements
Contribution of Reviewer(s)
Synopsis
Characteristics of included studies
Table 01 results
References to studies included in this review
Additional references
Typical Systematic Review
“Skeleton”
Steps to do
• Well-Formulated Question
• Efficient Search Strategies
• Review Abstracts to Determine Eligibility
• Apply Strict Inclusion/Exclusion Criteria
• Extract the Data
• Perform the Required Analyses (Meta-
analysis)
• Interpret the Results
• Determine Implications for Health Care Policy
Methodology
• At least 3 reviewers
• 7 peer reviewers
• Trial design characteristics
• Why included / excluded
• Quality of included studies in details
Some Controversies About Meta-Analysis
• Quality of Studies
• Many Small Studies or One Big Study?
• Publication Bias
Retrospective
• Try to make it prospective
• the first prospective systematic review in
the entire field of gynecology. (Al-Inany &
Aboulghar)
Repeat the analysis
• Excluding the unpublished studies (if there
were any)
• Excluding studies of the lowest quality
• If there were one or more very large studies,
the analysis would be repeated excluding
them to look at how much they dominate
the results.
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 patient
• Generalizability of results can be questioned.
Publication Bias
Human Albumin Model
• The objective was to review the
effectiveness of human albumin
administration in prevention of severe
ovarian hyperstimulation syndrome
Search strategy
• MEDLINE,
• EMBASE,
• The MDSG specialised register
• Abstracts from conferences
• handsearching of core journals
• contact with authors of relevant papers.
• Selection criteria
• Only randomised controlled studies
R.R
NNT
• 2.2% in albumin group / 7.7% in control
group
• absolute risk reduction was 5.5%
• NNT = 1/ARR
• For every 18 women at risk of severe
OHSS, albumin infusion will save one more
case.
Caution
• Whether this NNT would justify the
routine use of albumin infusion in cases
at risk of severe OHSS needs to be
judged by clinical decision makers.
Keep in mind
Evidence may change with more trials
challenges for systematic reviews
• Evidence into practice
• Many interventions reviewed cannot be
implemented in resource-poor situations
Developing Countries
• Most interventions reviewed so far don’t
reflect developing world priorities
• very few studies that have been conducted
in a developing country
• Most developing country research that is
found is excluded on quality grounds
Problems in Contribution
• Lack of EBM awareness
• Lack of training workshops
• Lack of Financial resources
• Lack of access to information
Major problem
• “Applied for grant but was refused on
basis of this not being research in real
sense and just a review of literature”
Solutions: I
• Systematic reviews are now recognized as a
2ry research
• Hence, the Cochrane collaboration changed
the name of the contributor from reviewer
to author
Solutions: II
• Address priority topics
• it is vital to invest in health care that works (for
limited resources)
• Disseminating the findings of systematic
reviews to policymakers
Useful websites
• Systematic Reviews Training Unit
http://www.ich.ucl.ac.uk/srtu
• NHS Centre for Reviews & Dissemination
http://www.york.ac.uk/inst/crd/welcome.htm
• Centre for Evidence-Based Medicine
http://cebm.jr2.ox.ac.uk/
Thank You
Where we stand!!!
• “Generally still biased to developed
world topics in The Cochrane Library.
• “Contributors from developing
countries have an important role in
creating a balance between ideal and
practical when their insights are
incorporated in reviews”

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systematic review : why & How

  • 2. What is a systematic review? • It is a structured review integrating pooling the results (Meta-analysis) of individual studies addressing the same topic.
  • 3. Systematic Review • structured : for consistent presentation of information • Meta-Analysis : combine and statistically summarize the results of individual studies
  • 4. Cook, D. J. et. al. Ann Intern Med 1997;126:376-380 Differences between Narrative Reviews and Systematic Reviews
  • 5. QUESTION Broad Focused SOURCES/ Usually unspecified Comprehensive; SEARCH Possibly biased explicit SELECTION Unspecified; biased?Criterion-based; uniformly applied APPRAISAL Variable Rigourous SYNTHESIS Usually qualitative Quantitative INFERENCE Sometimes Usually evidence- evidence-based based NARRATIVE SYSTEMATIC Cook, D. J. et. al. Ann Intern Med 1997;126:376-380
  • 6. Level of evidence • I–1 Systematic reviews. • I–2 One or more large double-blind randomised control trials. • II–1 One or more well-conducted cohort studies. • II–2 One or more well-conducted case-control studies. • II–3 uncontrolled experiment. • III Expert opinion. • IV Personal experience
  • 8. Why on the Top • Rigorous methodology • Peer reviewed • Relatively large sample size • Ensures the highest quality evidence
  • 9. Why do we need it • Too much trials • 25000 biomedical journals in print • 8000 articles published per day • All studies not equally well designed or interpreted
  • 10. So, we need a study of studies • To summarize evidence from studies that address a specific clinical question. • to explain differences among studies on the same question • In a way that limit bias (rigorous methodology & clear reporting)
  • 11. Example • Protocols in neurology units - 80% still recommend bed rest after LP • Systematic review of 10 trials of bed rest after spinal puncture – no change in headache with bed rest – Increase in back pain Serpell M, BMJ 1998;316:1709–10
  • 12. Why do we need it • many single trials had relatively low power • avoid Type II error: Investigators did not detect a difference when a difference actually exists • This is not surprising as the power to detect a difference will have been increased by the increase in the sample size
  • 13. Graphic Display: ß blockers in secondary prevention after myocardial infarction.
  • 14. Why do we need it • Systematic reviews help us to avoid the personal bias inherent in traditional reviews and expert opinion
  • 15. Why do we need it Example Mitchell JRA. Timolol after myocardial infarction: an answer or a new set of questions? BMJ 1981;282:1565- 70: "despite claims that they reduce arrhythmias, cardiac work, and infarct size, we still have no clear evidence that ß blockers improve long-term survival after infarction despite almost 20 years of clinical trials."
  • 17. Why do we need it • Results from systematic reviews are the cornerstone for developing practice guidelines
  • 19. Cochrane Library • The current resource with the highest methodological rigor – $235/year or abstracts only • www.cochrane.org • Specific point: e.g role of albumin in OHSS
  • 20. Abstract Background Objectives Criteria for considering studies for this review Types of participants Types of intervention Types of outcome measures Types of studies Search strategy for identification of studies Methods of the review Description of the studies Methodological qualities of included studies Results Discussion Conclusions Implications for practice Implications for research Internal sources of support to the review External sources of support to the review Potential conflict of interest Acknowledgements Contribution of Reviewer(s) Synopsis Characteristics of included studies Table 01 results References to studies included in this review Additional references Typical Systematic Review “Skeleton”
  • 21. Steps to do • Well-Formulated Question • Efficient Search Strategies • Review Abstracts to Determine Eligibility • Apply Strict Inclusion/Exclusion Criteria • Extract the Data • Perform the Required Analyses (Meta- analysis) • Interpret the Results • Determine Implications for Health Care Policy
  • 22. Methodology • At least 3 reviewers • 7 peer reviewers • Trial design characteristics • Why included / excluded • Quality of included studies in details
  • 23. Some Controversies About Meta-Analysis • Quality of Studies • Many Small Studies or One Big Study? • Publication Bias
  • 24. Retrospective • Try to make it prospective • the first prospective systematic review in the entire field of gynecology. (Al-Inany & Aboulghar)
  • 25. Repeat the analysis • Excluding the unpublished studies (if there were any) • Excluding studies of the lowest quality • If there were one or more very large studies, the analysis would be repeated excluding them to look at how much they dominate the results.
  • 26. 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 patient • Generalizability of results can be questioned.
  • 28. Human Albumin Model • The objective was to review the effectiveness of human albumin administration in prevention of severe ovarian hyperstimulation syndrome
  • 29. Search strategy • MEDLINE, • EMBASE, • The MDSG specialised register • Abstracts from conferences • handsearching of core journals • contact with authors of relevant papers.
  • 30. • Selection criteria • Only randomised controlled studies
  • 31. R.R
  • 32. NNT • 2.2% in albumin group / 7.7% in control group • absolute risk reduction was 5.5% • NNT = 1/ARR • For every 18 women at risk of severe OHSS, albumin infusion will save one more case.
  • 33. Caution • Whether this NNT would justify the routine use of albumin infusion in cases at risk of severe OHSS needs to be judged by clinical decision makers.
  • 34. Keep in mind Evidence may change with more trials
  • 35. challenges for systematic reviews • Evidence into practice • Many interventions reviewed cannot be implemented in resource-poor situations
  • 36. Developing Countries • Most interventions reviewed so far don’t reflect developing world priorities • very few studies that have been conducted in a developing country • Most developing country research that is found is excluded on quality grounds
  • 37. Problems in Contribution • Lack of EBM awareness • Lack of training workshops • Lack of Financial resources • Lack of access to information
  • 38. Major problem • “Applied for grant but was refused on basis of this not being research in real sense and just a review of literature”
  • 39. Solutions: I • Systematic reviews are now recognized as a 2ry research • Hence, the Cochrane collaboration changed the name of the contributor from reviewer to author
  • 40. Solutions: II • Address priority topics • it is vital to invest in health care that works (for limited resources) • Disseminating the findings of systematic reviews to policymakers
  • 41. Useful websites • Systematic Reviews Training Unit http://www.ich.ucl.ac.uk/srtu • NHS Centre for Reviews & Dissemination http://www.york.ac.uk/inst/crd/welcome.htm • Centre for Evidence-Based Medicine http://cebm.jr2.ox.ac.uk/
  • 43. Where we stand!!! • “Generally still biased to developed world topics in The Cochrane Library. • “Contributors from developing countries have an important role in creating a balance between ideal and practical when their insights are incorporated in reviews”

Editor's Notes

  • #4: Just read the slide – and try to elicit answers.
  • #10: The lag period between publication of research findings demonstrating clinical effectiveness and the subsequent implementation in clinical practice is well recognized. Practitioners continue to base clinical decisions on outdated training and on experience with individual patients.