Systematic Review
and
Meta-analysis
Agustini Utari
Dept. of Pediatrics
Faculty of Medicine-Diponegoro University
Semarang
2023
Medical literature reviews
Systematic
Overview Review
Meta-analysis
(Review à In gathering,
Article) evaluating, à SR + formal
presenting statistical
à evidence analysis
unsystematic
à No formal
statistical analysis
(Unsystematic) Review VS Systematic Review
Not focused on one Focused on only one
interested topics of interest
topic(broader) Diagnosis, etiology,
Mechanism of disease prognosis and
No criteria for treatment
selection of articles to Explicit methods and
be reviewed (bias+) criteria for selection
No assessment of (database, keywords,
selected articles types of articles)
Low applicability in Assessment of
clinical practice selected articles
Highly applicable
Steps on SR
Formulating answerable question (PICO)
Extensive and comprehensive search the evidence
- 2/> major database
- Specific keywords
- Selection criteria
(inclusion & exclusion) articles, year of
publication, language
Critically appraise the evidence à quality assessment
à 2/> assessors
Synthesis and analysis à meta-analysis
Discuss and conclude the results
Asking Answerable Clinical
Questions(PICO)
Patient: For which patient/problem do you need
information?
Intervention: What medical event do you need to
study the effect of?
Comparison: What is the evidence that the
proposed intervention produces better or worse results
than no intervention at all, or a different type of
intervention?
Outcome: What is the effect of the intervention?
PubMed and MEDLINE
PubMed:
• A service of National Library of Medicine (NLM)
• Provides access to over 23 million citations and
abstracts from MEDLINE and additional life sciences
journals.
• Includes links to many sites providing full text articles
and other related resources.
MEDLINE:
The U.S. National Library of Medicine‘s (NLM) premier
bibliographic database
Contains citations and abstracts from life sciences journals
and NOT full-text articles from approximately 5,600
worldwide journals in 39 languages; 60 languages for older
journals
Define “Key-Words”
Based on PICO component
Use MeSH in PubMed
Componen of SR/MA
Introduction
Methods
Results
Discussion and Conclusion
Introduction
State the reasons why the review is
needed à based on problems in clinical
setting (high volume, high risk, high cost)
Any controversies in the literatures?
à In treatment, choice of diagnostic
modalities, determination of prognosis
Ended with objective of SR based on
clinical question (PICO)
Methods
How the individual studies searched and
selected
How to appraise/assess the individual
studies
How to combine (synthesis)
Searching the literatures
A comprehensive and reproducible literature
search is the foundation of a systematic
review
Search for published studies at least in
MEDLINE, EMBASE, and CINAHL.
Search for unpublished clinical trials in the
Cochrane Central Register of Controlled
Trials (CENTRAL) or other clinical trial
database (www.clinicaltrial.gov)
Secondary/hand searching
No limitation on years and languages
Literature Search Challenges
Database Bias - “No single database is likely to
contain all published studies on a given subject.”
Publication Bias - selective publication of
articles that show positive treatment of effects
and statistical significance.
à Hence, it is important to search for
unpublished studies through a manual search
of conference proceedings, correspondence
with experts, and a search of clinical trials
registries.
Literature Search Challenges
English-language bias - occurs when
reviewers exclude papers published in
languages other than English
Citation bias - occurs when studies with
significant or positive results are referenced
in other publications, compared with studies
with inconclusive or negative findings
Quality Assessment
The validity of a systematic review ultimately
depends on the scientific method of the retrieved
studies and the reporting of data
In systematic review to assess treatment effect,
RCTs are considered to be more rigorous than
observational studies
A review based on well-designed RCT will likely
be more valid and accurate than a review based
on observational studies or case reports
Quality Assessment (con’t)
• Quality assessment should be
performed by at least two assessors
• The most common way to assess and
report study quality has been using a
composite, numerical scoring
instrument ( Ex : Jadad score)
Jadad score
Randomization (2 points possible)
1 point if study described as randomized
Add 1 point if randomization method described and
appropriate (e.g. random numbers generated)
Deduct 1 point if randomization described and inappropriate
Double-blinding (2 points possible)
1 point if study described as double-blinded
Add 1 point if method of double-blinding described and
appropriate
Deduct 1 point if double-blinding described and inappropriate
Withdrawals (1 point possible)
Give 1 point for a description of withdrawals and drop-outs
Results
Result of search strategies (flow diagram)
Result of quality assessment
Synthesis (summarized the effects)
Heterogeneity
Studies brought together in a systematic
review will differ.
“Any kind of variability among studies in a
systematic review”
Variability in the participants, interventions and
outcomes studied à clinical heterogeneity
Variability in study design and risk of bias à
methodological heterogeneity
Variability in the intervention effects being
evaluated in the different studies à
“statistical heterogeneity”
Heterogeneity
chi-squared (χ2, or Chi2) test à is
included in the forest plots
low P value provides evidence of
heterogeneity of intervention effects
This means that while a statistically
significant result may indicate a problem
with heterogeneity
P value of 0.10 à used to determine
statistical significance.
Degree of heterogeneity (I2 )
Reporting Bias
THANK YOU