1. Systematic review an overview and posing the question
Dr. Will Whiteley
CSO Clinical Academic Training Fellow
Division of Clinical Neurosciences, University of Edinburgh

2. Why review the literature systematically?
We often need to make sense of multiple studies addressing the same question
We can either pick those studies that most agree with our preconceptions or make an unbiased assessment of as many of the studies as possible
The unbiased approach is known as systematic review, and when done well can lead to the most reliable synthesis of the data.

3. Cumulative meta-analysis Expert opinion
RCTs - clear benefit
Experts follow
The use of thrombolysis in myocardial infarction

4. Proteus effect
Early extreme contradictory estimates may appear in published research: The Proteus phenomenon in molecular genetics research and randomized trials John P.A. Ioannidisa, Thomas A. Trikalinosa

5. Systematic review aims to:
answer a specific question,
reduce bias in the selection and inclusion of studies,
appraise the biases of the included studies
to summarise them objectively
commonly require more time and people than narrative reviews

6. Systematic review – a medical novelty?
astronomy
Imperial army medicine
quantum physics
psychology,
education,
criminology,
agriculture, ….

7. Sir R.A. Fisher Karl Pearson
‘To call in the statistician after the experiment is done may be no more than asking him to perform a post-mortem examination: he may be able to say what the experiment died of’

8. Advantages and disadvantages of systematic review to your research projects
A systematic review of your research question will take longer than a simple narrative review
The results of your systematic review (even if in includes a meta-analysis) may be wrong
65%
70%
Discrepancies between meta analysis and subsequent randomised controlled trials N Engl J Med 1997;337:

9. However, a systematic review is more likely to be published and cited than a narrative one!

10. Systematic review – overview of process
Clear question to answer, and pre-specified selection criteria
Clearly defined methods for data extraction – to remove as much bias as possible from the data selection process
Comprehensive search of the published (and if time available unpublished) literature – to ensure ‘negative’ studies are found which might not be published in the top tier journals
Duplication of data extraction and study selection
Summary estimation – if sufficient high quality studies are found

11. Posing the research question
In neurologically asymptomatic people, what is the prevalence of imaging findings on high resolution brain MR images?
e.g.
Patients
Intervention
Control
Outcome
Decide what type and quality of studies you will accept; this will be different for an established treatment to a new biomarker of disease
A good question will help to define your search strategy and study selection
In patients within one week after ischaemic stroke, what is the prognostic value of IL6 for disability or death?
In patients within 48 hours of subarachnoid haemorrhage, what is the value of oral simvastatin compared to control for prevention of radiological vasospasm?

12. Data extraction
Decide prior to looking at the literature what data you will need to answer your question
What is likely to contribute to study related heterogeneity
Design a form – either paper or in the database program of your choice
Make sure it is attractive and easy to fill in
Go through a few iterations of design
Data extract in duplicate (choose a helpful colleague)

13. Measuring bias
Most study designs have potential for bias that can be minimised by taking appropriate precautions
‘Quality’ is a measure of this bias
Set a ‘quality threshold’ for inclusion
e.g. prospective cohort studies only or
Investigate effect of quality on outcome
Quality measures are available for a number of study designs
Prospective observational studies MOOSE
Diagnostic studies STARD
Randomised controlled trials QUORUM
Genetic associations HuGE reviews etc. etc.

14. In summary
Systematic review aims to reduce bias in assessing literature
Select you question carefully – make sure it is answerable
Pre-specify your methods of study selection and data-extraction
Perform your search strategy ….