Introduction to Systematic Review & Meta-Analysis

Assoc. Prof. Dr.
Hasanain Faisal Ghazi
• MBChB (University of Baghdad)
Master & PhD (UKM, Malaysia)
• Publication:
89 Full papers (56 in SCOPUS)
H Index = 11
• Published Systematic Review & Meta
Analysis (7)
• Editor in Chief, Global Journal of Public
Health Medicine.
@AP_Dr_Hasanain_Faisal_Ghazi 2

INTRODUCTION
Why We Do Sys. Rev. ??????
@AP_Dr.Hasanain_Ghazi

Evidence-based medicine
• Is the process of systematically reviewing, appraising, and using
clinical research findings to aid the delivery of optimum clinical care
to patients.
Clinical
Judgment
Relevant
scientific
evidences
Patient values
& preferences
EBM

Definition
• A systematic review summarises the results of available carefully
designed healthcare studies (controlled trials) and provides a high
level of evidence on the effectiveness of healthcare
interventions. Judgments may be made about the evidence and inform
recommendations for healthcare.
Reference: https://consumers.cochrane.org/what-systematic-review

SR & MA
• A systematic review answers a defined research question by
collecting and summarising all empirical evidence that fits pre-
specified eligibility criteria.
• A meta-analysis is the use of statistical methods to summarise the
results of these studies.

WHAT IS SYSTEMATIC REVIEW
• Focus on specific question
• use explicit , pre-planned scientific methods to:
1. Identify
2. Select
3. Appraise
4. Summarize similar but separate studies

Must Have
• clearly stated objectives with pre-defined eligibility criteria for studies
• explicit, reproducible methodology
• a systematic search that attempts to identify all studies
• assessment of the validity of the findings of the included studies (e.g.
risk of bias)
• systematic presentation, and synthesis, of the characteristics and
findings of the included studies

SYSTEMATIC
REVIEW
META ANALYSIS
TRADITIONAL
NARRATIVE
REVIEW

TRADITIONAL NARRATIVE REVIEW
• No standard format
• No specific methods for selecting and appraising
• Quantitively synthesis rarely used to integrate information from
multiple studies

SR Steps
1. Gather your team
2. Develop protocol
3. Data collection, locate and screen

4. abstract data , appraise risk of Bias
5. synthesis findings and interpret
6. report writing
7. update

META ANALYSIS
• Is an OPTIONAL component of systematic review.
• A statistical analysis which combines the results of several
independent studies considered by the analyst to be combinable
(Huque, 1988).

What meta analysis can help
• Assess strength of evidence
To determine whether an effect exists in a particular direction
• Combine results quantitively
To obtain a single summary result
• Investigate heterogeneity
To examine reasons for different results among studies

Addressing same question?
• What is the effect of interferon therapy in hepatitis C?
• Size of effect might be higher when participants are older, more
educated or healthier than others
• Different forms of interferon
• Different interferon doses
• Different viral subtypes of hepatitis C

WHEN TO DO MA??
• When more than 1 study has estimated a treatment effect or
association.
• When the difference in study characteristics are unlikely to effect
treatment effect.
• When the treatment effect have been measured and reported in similar
ways (or when data available) .

WHO IS DOING SYS. REV.
• Independent authors
• Cochrane collaboration
• Group interested in policy
• Business

Who is using Sys Rev
• Individual doctors and researchers
• Patient and consumers
• Guidelines producers
• Policy makers

IOM standers for systematic reviews
• Initiating a systematic review
• Establish a review team
• Manage bias and conflict of interest of the review team
• Ensure stakeholder input
• Manage bias and conflict of interest of those providing input
• Formulate the topic
• Develop the protocol
• Submit the protocol for peer review
• Make protocol publicly available

Formulate the Topic
• Confirm the need for a new review
• Develop an analytic framework
• Use a standard format to articulate each question of interest For
example, PICO(TS)
• State a rationale for each question
• Refine each question

Formulating the Question in a Systematic
Review
• “The most important maxim for data analysis to heed, and one which
many statisticians have shunned is this: ‘far better an approximate
answer to the right question, which is often vague, than an exact
answer to the wrong question, which can always be made precise.’”

Ways Similar Studies May Differ
• Patient population
• Inclusion and exclusion criteria
• Exposure definition/intervention composition, dose, timing
• Comparison group/controls
• Management protocol(co interventions) for trials
• Outcome definition(follow-up time, cause-specific mortality)
• Quality of design and execution
• Analysis

Components of well-structured question
• P patients or population
• I intervention/ exposure
• C comparison groups (s)
• O outcome

Type of people
• Define condition or disease, including explicit diagnostic criteria
• Population and setting of interest (age, race, sex, community, hospital,
outpatient)

Type of risk factors
• Timing of exposure
• Route of administration
• Dose of intensity
• Duration of exposure or therapy

Type of comparison group
• For trials :
• Placebo
• Standard therapy
• No treatment
• For epidemiological STUDIES
• No exposure
• Non-cases (hospital, neighborhood, etc)

Types of outcome
• Criteria of defining
• Important to consumers, providers
• Unpublished data

Well constructed and answerable clinical
question
• For preschool children with mild to moderate visual acuity
impairment, are glasses and patching effective in improving visual
acuity, compared with glasses alone or no treatment ?

Some groups add TS to PICO
• T= TIMING (Duration of minimum of follow up)
• S= sitting (primary care, specialty, inpatients )

• Effectiveness best answered with RCT
• Harm best answered with RCT but usually more practical to use
observational data (rare events, occurring after follow-up complete in
an RCT)

EXAMPLES

RESEARCH QUESTION
IS Drug therapy associated with long term morbidity and mortality in older
persons with moderate hypertension?
• P = older persons with moderate hypertension
• I= drug therapy
• C= not stated ( presumably any intervention other than named drug therapy
• O= long term morbidity and mortality

Finding the evidence

Major databases
• Major bibliographic databases for RCT
• Medline/Pubmed
• EMBASE
• Cochrane central register for controlled trials
• National and regional databases
• Subject specific datbases
• CINAHL
• PsychINFO
• OTSeeker

Citation databases
• Web of science
• SCOPUS
• Dissertation (ProQuest)

Register of ongoing trials
• www.clinicaltrials.gov
• www.centerwatch.com
• www.controlles-trials.com
• WHO Portal

Break into concepts
• P POPULATION
• I INTERVENTION
• C COMPARISON
• O OUTCOME

Patients with choroidal neovascularization associated with age related macular degeneration, do
intravitreal injections of Lucentis , when compared with Avastin , prevent vision loss?
Individuals with choroidal neovascularization associated with
age related macular degeneration
Lucentis (Ranibizumab)
Avastin
Change in visual acuity or visual field
P
I
C
O

• START WITH GENERAL FORMAT:
• (Population OR synonym #1 OR synonym #2) AND
• (Intervention OR synonym #1 OR synonym #2) AND
• (Comparison OR synonym #1 OR synonym #2) AND
• (Outcome OR synonym #1 OR synonym #2) AND
• Add study type filters

Documenting the search
• Bibliographic software management
• Endnote
• Mendely
• QUOSA

• WHEN DID THE SEARCH
• Month/year
• Where you searched
• Electronic databases
• Hand searches
• Trial registers
• Internet
• bibliographies

• How you searched
• Strategies
• What you found
• PRISMA flow diagram

PRISMA
http://www.prisma-statement.org/
Preferred Reporting Items for Systematic Review and Meta-analysis

Assessing the risk of BIAS

ELEMENTS OF STUDY QUALITY THAT CAN
BE ASSESSED BY READING STUDY REPORT
• INTERNAL VALIDITY
• EXTERNAL VALIDITY
• RELEVANCE, ORIGINALITY
• ETHICS

BIAS
• SELECTION BIAS
• INFORMATION BIAS
• ANALYSIS

META ANALYSIS

• A meta-analysis is a survey in which the results of the studies included
in the review are statistically similar and are combined and analysed as
if they were one study.

PLANNING THE ANALYSIS
• Results of meta analysis can be very misleading if suitable attention
has not been given to:
• Formulate the review question
• Specify eligibility criteria
• Identify, select and critically appraise studies
• Collect appropriate data
• Decide what would be meaningful to analyze

• Systematic review contain analysis of the primary studies
• Qualitative: structured summary, description , and discussion of the
studies characteristics that may affect the cumulative evidence
• Quantitative: involves statistical analysis( meta-analysis)

A general framework for synthesis
• What is the direction of effect (association )
• What is the size of effect?
• Is the effect consistent across studies ?
• What is the strength of evidence for the effect ?

What is meta analysis
• An optional component of systematic review
• Definition:
• The statistical analysis of a large collection of analysis results from
individual studies for the purpose of integrating the findings (Glass 1976)
• The statistical analysis which combines the results of several independent
studies considered by the analyst to be combinable (Huque, 1988)

Data presentation
• FOREST GRAPHS
• FUNNEL PLOTS
• RADIAL PLOTS

Reference : Hoffman, J. I. E. (2015). Meta-analysis. Biostatistics for Medical and Biomedical
Practitioners, 645–653. doi:10.1016/b978-0-12-802387-7.00036-

• Typical figure of response to some new treatment. The dots are the
mean log odds ratio, and the horizontal lines indicate 95% confidence
limits. Figures in the right-hand column are the weights assigned to
each study; the studies are often arranged in descending weights. The
solid vertical line at 0 indicates no difference between the groups, and
the dashed vertical line indicates the pooled average. Some figures
include the numbers of subjects in each group.

Note on interpretation
• The results of meta-analysis (estimate and confidence interval ) as any
other study must be interpreted in the context of a clinically important
effect size
• Statistically significant result may not be clinically important
• Results that is not statistically significant may still be compatible with
a clinically important effect

Why we do meta analysis
1. Increase power and precision (detect effect as statistically significant)
2. Quantify effect sizes and their uncertainty
Reduce problems of interpretation due to sampling variation
3. Assess homogeneity / heterogenicity of results
4. Answer questions not posed by individual studies

CONCLUSION
• Systematic review is essential for healthcare
• Meta analysis is an optional thing in SR
• SR should be done in team

• Cochrane is a British
international charitable
organisation formed to
organise medical research
findings to facilitate
evidence-based choices
about health interventions
involving health
professionals, patients and
policy makers. It includes
53 review groups that are
based at research
institutions worldwide

Introduction to Systematic Review & Meta-Analysis

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Introduction to Systematic Review & Meta-Analysis