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An Introduction to Systematic Reviews

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Title: An Introduction to Systematic Reviews


1
An Introduction to Systematic Reviews
2
Information explosion
3
Daily
  • 46 RCTs
  • 1000 Medline New articles
  • 6,000 biomedical articles

4
Annually
  • 3 million articles
  • 30,000 journals

5
Increasing Knowledge
6
  • Most research published in medical journals is
  • too poorly done
  • or
  • insufficiently relevant
  • to be clinically useful

7
Too much information, too little time
  • There is simply too much information around for
    people to keep up to date.
  • On top of this, high quality information is often
    not easy to find.

8
Review articles
9
  • A review is the generic term for any attempt to
    synthesis the results and conclusions of two or
    more publications on a given topic.

10
  • Some reviews are usually based on narrative or
    commentary and are produced by a
  • content expert

11
  • Whats the problem with
  • Expert Opinion?

12
  • Professor Paul Knipschild has described how
    Nobel prize winning biochemist Linus Pauling used
    selective quotes from the medical literature to
    "prove" his theory that
  • vitamin C helps you live longer and feel better.

13
  • When Knipschild and his colleagues searched the
    literature systematically for evidence
  • They found that

14
  • One or two trials did strongly suggest that
    vitamin C could prevent the onset of the common
    cold.
  • There were far more studies which did not show
    any beneficial effect.

15
  • Unfortunately, expert reviewers often
  • Make conflicting recommendations
  • Their advice frequently lags behind
  • Inconsistent with the best available evidence.

16
  • The use of unsystematic approaches to collecting
    and summarizing the evidence.

17
  • In one study, self-rated expertise was
    inversely related to the methodologic rigor of
    the review
  • Oxman AD, Guyatt GH. The science of
    reviewing research. Ann N Y Acad Sci.
    1993703125-133 discussion 133-134.

18
The problems are that
  • Too much information, too little time
  • Many too poorly done or insufficiently relevant
    to be clinically useful
  • Many have conflicting results
  • On top of these, high quality information is
    often not easy to find

19
Timely response
  • A classic example streptokinase in myocardial
    infarction
  • First trial published in 1959
  • 15 trials published up to 1977
  • Introduced as normal practice in late 80s
  • Meta-analysis of treatments in 1992 fall in
    mortality by 1977, after inclusion of 15 trials

20
Thrombolytic Therapy
Textbook/Review Recommendations
0.5
1.0
2.0
Cumulative
RCTs
Pts
Year
1 23
Not Mentioned
1960
Experimental
Rare/Never
Routine
Specific
2 65
1965
3 149
21
5
4 316
1970
7 1793
10
1
1
2
10 2544
Plt.01
11 2651
15 3311
8
2
17 3929
22 5452
7
23 5767
8
1980
1
12
27 6125
Plt.001
8
M
30 6346
4
1
1985
33 6571
M
7
3
1
43 21 059
M
54 22 051
Plt.00001
2
2
5
1
M
65 47 185
67 47 531
1
8
15
M
70 48 154
1990
M
1
6
Odds Ratio (Log Scale)
Favours Treatment
Favours Control
21
Bias
  • Bias means something that will cause a
    consistent deviation from the truth.
  • This is different from the play of chance.

22
  • There are three possible sources of bias in
    reviews
  • bias arising from the studies included in the
    review
  • bias arising from the studies not included in the
    review
  • Bias arising from the way the review is done.

23
Minimizing bias
  • We need to do as much as possible to minimize
    the effects of anything that will cause the
    results to deviate from the truth.

24
What is a Systematic Review?
25
Systematic review Or Overview
  • Comprehensively
  • locates
  • evaluates
  • synthesizes
  • all the available literature on a given topic
  • using a strict scientific design which
  • must itself be reported in the review

26
A systematic review, therefore, aims to be
  • Systematic (e.g. in its identification of
    literature)
  • Explicit (e.g. in its statement of objectives,
    materials and methods)
  • Reproducible (e.g. in its methodology and
    conclusions)

27
  • The systematic part of systematic reviews is
    all about
  • minimizing bias in the way
  • the review is carried out

28
Systematic reviews are the same as ordinary
reviews, only bigger!
  • not simply "comprehensive"
  • but to answer a specific question
  • to reduce bias in the selection and inclusion of
    studies (language, database, publication,
    reporting, citation, multiple publication)
  • to appraise the quality of the included studies
  • Internal validity minimised systematic error
    (bias)
  • External validity generalisability of findings
  • to summarise them objectively

29
  • They are different!!

30
  • The UK Medical Research Council now requires
    a systematic review has been prepared before it
    will commission a new trial.
  • The question has not already been answered
  • The results of previous research are used in
    designing the new trial.

31
The Cochrane Collaboration www.cochrane.org
32
Archie Cochrane
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.
33
Section 2
34
Conducting a Systematic Review
35
Stages of a systematic review
  • Planning the review i.e. identifying the need
    for a review, and documenting the methodology
  • Conducting the review i.e. finding, selecting,
    appraising, extracting and synthesising primary
    research studies
  • Reporting and dissemination i.e. writing up and
    disseminating the results of the review

36
Development of a review protocol
37
Formulating review questions
Searching selecting studies
Study quality assessment
Extracting data from studies
Data synthesis
38
Step 0
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39
Formulating review questions
  • The first and most important decision in
    preparing a review is to determine its focus
  • This is best done by asking clearly framed
    questions.

40
Formulating review questions
  • define a four part clinical question

breaking the question down into its component
parts
41
Question components PICO
  • What types of Participants?
  • What types of Interventions?
  • What types of Comparison?
  • What types of Outcomes?

42
A PICO question
Time-consuming question
  • What is the best strategy to prevent smoking
    in young people?

43
An answerable question
  • Q. Are mass media (or school-based or
    community-based) interventions effective in
    preventing smoking in young people?

44
How are these questions different?
  • Does aspirin improve survival after acute
    myocardial infarction?
  • In patients with acute myocardial infarction,
    does daily, low-dose, oral aspirin lead to higher
    survival rates as compared to placebo?

45
Formulation of a therapy question
Intervention
Outcome
Is Zinc effective in treating cold?
Intervention
Patient/problem
In children with common cold, is oral Zinc
effective in reducing the duration of symptoms,
as compared to placebo?
RCTs
Outcome
Comparison
46
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47
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48
Selecting studies
  • performing a comprehensive, objective, and
    reproducible search of the literature
  • selecting studies which meet the original
    inclusion and exclusion criteria
  • can be the most time-consuming and challenging
    task in preparing a systematic review

49
Data sources for a systematic review
  • Electronic databases
  • MEDLINE and EMBASE
  • Specialized or local databases (CINAHL, CENTRAL,
    AMED,)
  • Hand searching
  • Grey literature ( thesis, Internal reports,
    pharmaceutical industry files)
  • Checking reference lists
  • Unpublished sources known to experts in the
    specialty (seek by personal communication)
  • Raw data from published trials

50
Developing a search strategy
  • It is always necessary to strike a balance
    between comprehensiveness and precision when
    developing a search strategy.

51
Selecting studies
  • assessing titles and abstracts
  • full text

52
Searching the literature
  • Published and unpublished literature
  • unbiased search (not just Medline which contains
    lt half of trials)
  • conference papers, company reports, et.
  • personal communication with experts

53
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54
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  • ?????????? ?????(UN-WHO)
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  • IRAN MEDEX
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  • Cochrane Library
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55
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  • AIDS
  • HIV
  • Knowledge
  • Attitude
  • Knowledge/ Attitude/practice
  • Risk factors
  • Intra venous drug use (IDU)
  • High risk sex
  • Sex workers, heterosexual, homosexual, MSM
  • STI
  • IRAN
  • Prevalence
  • relative risk,odds ratio, effect
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56
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    form.doc

57
  • Experts in a particular area frequently have
    pre-formed opinions that can bias their
    assessments of both the relevance and validity of
    articles

58
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59
Assessment of study quality
  • Assess each study for
  • eligibility for inclusion
  • study quality
  • reported findings
  • Ideally will involve two independent reviewers

60
Assessment of study quality
  • Validity the degree to which the trial design,
    conduct, analysis, and presentation have
    minimized or avoided systematic biases.

61
'Quality' scales and checklists
62
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63
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64
Collecting data
  • data collection forms
  • Methods
  • Participants
  • Interventions
  • Outcome measures and results

65
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66
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67
Graphical Display
  • The graphical display of results from individual
    studies on a common scale is a Forest plot.
  • In the forest plot each study is represented
    by a black square and a horizontal line
    (CI95).The area of the black square reflects
    the weight of the study in the meta-analysis.
  • Forest plot is an important step, which allows
    a visual examination of heterogeneity between
    studies.

68
Odds Ratio
Line of no significance
69
Odds Ratio with pooled effect size
Best/point estimate
Confidence Interval
70
Forest Plot
71
Forest Plot
72
Meta-Analysis
  • when an overview incorporates a specific
    statistical strategy for assembling the results
    of several studies into a single estimate

73
  • Systematic reviews do not have to have a
    meta-analysis
  • There are times when it is not appropriate or
    possible.

74
  • The term meta-analysis is often used
    interchangeable with systematic review, it is
    actually a statistical technique used to combine
    the results of several studies addressing the
    same question into a single summary measure (Khan
    et al., 2000).

75
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76
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77
A Range of Function of Systematic Review
  • 1- Identify heterogeneity in effects among
    multiple studies and, where appropriate, provide
    summary measure.
  • 2- Increase statistical power and precision to
    detect an effect
  • 3- Develop, refine and test hypothesis
  • 4- Reduce the subjectivity of study comparisons
    by using systematic and explicit comparison
    procedure

78
Remain
  • 5- Identify data gap in the knowledge base and
    suggest direction for future research
  • 6- Calculate sample size for future studies

79
Section 3
80
Steps of a systematic review
  • Step 1 Framing question for a review
  • Step 2 Identifying relevant literature
  • Step 3 Assessing the quality of the literature
  • Step 4 Summarizing the evidence
  • Step 5 Interpreting the finding

81
  • The principal findings should be related to the
    main question formulated in step1.
  • Other finding should be considered secondary.

82
Validity of the main finding
  • Are the searches adequate?
  • Is there a risk of publication and related
    biases?
  • Is the quality of the included studies high
    enough?

83
Limitations of Systematic Review
  • Reporting bias and the inadequate quality of
    primary research are potentially serious problems
    for systematic reviews.
  • The dissemination of research findings is not a
    random process rather it is strongly influenced
    by the nature and direction of results.

84
Type of reporting bias
  • Publication bias
  • The publication or non-publication of research
    findings, depending on the nature and direction
    of the results

85
Publication bias
  • 1-Arising from the researchers deciding whether
    or not to submit result
  • 2- Arising from the tendency of journals to
    reject negative studies
  • 3-sponsorship
  • .

86
Methods of preventing publication bias
  • 1-Registeries
  • 2-Editorial policy

87
  • Time lag bias
  • The rapid or delayed publication of research
    finding, depending on the nature and direction of
    the results

88
  • Multiple (duplicate) publication bias
  • The multiple or singular publication of research
    finding, depending on the nature and direction of
    the results

89
  • Citation bias
  • The citation or non-citation of research
  • finding, depending on the nature and
    direction of the results

90
  • Language bias
  • The publication of research finding in a
    particular language, depending on the nature and
    direction of the results

91
  • Outcome reporting bias
  • The selective reporting outcomes but not of
    others , depending on the nature and direction of
    the results

92
Funnel Plot
  • Plots of the trials effect estimates against
    sample size, may be useful to assess the validity
    of meta-analyses
  • A symmetrical shape is expected, since greater
    scatter in estimate is expected for smaller
    study.
  • The cardinal sign of publication bias is a hole
    in the middle or one side of the plot, that is an
    area where we would expect to see study result
    but where there are apparently none.

93
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94
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