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

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

Cochrane LibraryCochrane 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

AbstractBackgroundObjectivesCriteria for considering studies for this reviewTypes of participantsTypes of interventionTypes of outcome measuresTypes of studiesSearch strategy for identification of studiesMethods of the reviewDescription of the studiesMethodological qualities of included studiesResultsDiscussionConclusionsImplications for practiceImplications for researchInternal sources of support to the reviewExternal sources of support to the reviewPotential conflict of interestAcknowledgementsContribution of Reviewer(s)SynopsisCharacteristics of included studiesTable 01 resultsReferences to studies included in this reviewAdditional 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 and

Practice

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 mindEvidence 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”