Systematic Review & Metaanalysis of interventional Studies
Comparative Effectiveness Research
Systematic Review !
Presenting results and ‘Summary of findings’
A. PRISMA flow chart
B. Forest plots
C. Summary of finding Tables
D. Baseline Tables.
Steps for Systematic review !
Collect your TEAM !
Defining the review
QUESTION
and developing
Criteria
for including studies
Searching the literature
Selecting studies
Data Extraction
Assessing risk of bias in included studies
Analyzing data and undertaking metaanalysis
Addressing reporting biases
Presenting results and ‘Summary of findings’ tables
Interpreting results and drawing conclusions
1. Defining your Question & Criteria
Clearly defined,
focused
review begins with a
wellframed question,
Sufficiently broad to encompass the likely diversity of studies, but sufficiently narrow to ensure that a meaningful answer can be obtained.
PICOs
Check the validity of your question
Documentation
2. Searching the Literature
Where & How?
Bibliographic databases (The Cochrane Central Register of Controlled Trials (
CENTRAL
),
PubMed
,
Web of Knowledge
,
SCOPUS
and
EMBASE
(if access is available)
Previous
reviews and guidelines
Trials registry
(unpublished work)
Search strategy >>
Identify relevant keyword
s >> Use
MeSH
to improve your keywords
Exporting your results & Remove duplicates
Documentation
Ahmed Elgebaly
MedSci, MBChB candidate, Faculty of Medicine AlAzhar University
Email: Ahmedelgebaly94@azhar.edu.eg
No. +201112987286
Rationale!

Invaluable
scientific activities?
 Separates the
redundant deadwood
from the studies that are worthy of reflection,
 2,000,000 annually!

Precise estimation & more power
 Decision makers! EBM!
 Streptokinase Example !

Guidelines and legislation !
Systematic review ?
 A systematic review attempts to
collate all empirical evidence
that fits
prespecified eligibility criteria
in order to answer a specific research question. It uses explicit,
systematic methods
that are selected with a view to minimizing bias, thus providing more reliable findings from which conclusions can be drawn and decisions made (Antman 1992, Oxman 1993).
Systematic review are:
 Clearly stated set of objectives with
predefined eligibility criteria
for studies;
 an explicit,
reproducible methodology
;
 a systematic search that attempts to identify all studies that would meet the eligibility criteria;
 an assessment of the validity of the findings of the included studies, for example through the assessment of risk of bias; and
 a systematic presentation, and synthesis, of the characteristics and findings of the included studies.
Metaanalysis ?
 The use of
statistical methods
to summarize the results of independent studies (Glass 1976).
 Provide more precise estimates of the effects of health care than those derived from the individual studies.
 Facilitate investigations of the consistency of evidence across studies
3. Selecting studies for eligibility
Screening
Assessment of eligibility of studies should be done by at least two people, independently.
Consider training your TEAM !! A typical process for selecting studies.
2 steps screening >> Title & Abstract screening >> Fulltext screening
Consider Multiple reports.
The most influential decisions.
Document excluded studies.
5. Data Extraction
Checklist of items to consider in data collection or data extraction
Outcome definitions.
It is strongly recommended that more than one person extract data from every report to minimize errors and reduce potential biases being introduced by review authors !!
Piloting your form.
Extract data from each report separately, then combine information across multiple data collection forms.
4. Assessing Risk of Bias
A. An assessment of the validity of studies included in a review should emphasize the risk of bias in their results.
B. What is bias?
C. Importance of ROB
D. We assess the Report NOT what have been actually done
E. Many tools but Cochrane recommend against the use of scales yielding a summary score.
5. Analysing data and undertaking metaanalyses
A. Metaanalysis is the
statistical combination
of results from
two or more separate studies.
B. Increase in
power,
improvement in
precision
, the ability to answer questions
not posed
by individual studies, and the opportunity to
settle controversies
arising from conflicting claims !
C. Types of data and effect measures (
Basic Statistical Concepts
)
D. Summarizing effects across studies (
MD, SMD, RR, OR
)
E. Heterogeneity
Twostage process
First Stage: Summary statistics of each study.
Second Stage: A pooled weighted average.
Study weight (
inverse variance method
)
Fixed vs. Random
Heterogeneity
Statistical heterogeneity is a consequence of
clinical or methodological diversity
More than one would expect due to
random error (chance) alone
MetaAnalysis !
Introduction to metaanalysis
Summary effect
Fixedeffect analysis
We assume that the
true effect size
is the
same
in all studies
Difference is due to
sampling errors
The summary effect is our estimate of this
common effect size
Randomeffects analysis
We assume that the
true effect size
varies
from one study to the next
Dispersion reflects
Real differences
Summary effect is our estimate of the
mean of these effects
.
Measuring Heterogeneity
Confidence Interval overlap
Chisquared (χ2, or Chi2) test
P > 0.1
Problems with small or few studies & large studies
Quantifying inconsistency
Isquare
0% to 40%: might not be important;
30% to 60%: may represent moderate heterogeneity*;
50% to 90%: may represent substantial heterogeneity*;
75% to 100%: considerable heterogeneity*.
Metaanalysis of continuous outcomes
We need Mean, SD, N
Inversevariance fixedeffect method and the inversevariance randomeffects method
Which measure ?
Mean Difference (MD)
All studies report the outcome using the same scale
Studies with small standard deviations are given relatively higher weight
Standardized mean difference (SMD)
Studies report the outcome using different scale
Standard deviations are used to standardize the mean differences to a single scale
MetaAnalysis of dichotomous outcomes
We need N of event & total N
What is event ?
RR & OR
RR = 3 ? or 0.25 ?
OR = 3
OR and RR are not the same
It is simplest to first convert it into a risk ratio
Risk difference
Straightforward to interpret
Number needed to treat
RR & OR may be usefully converted to NNTs
Ordinal outcomes and Measurement scales
Specialist methods are not available in RevMan
Longer ordinal scales are often analysed in metaanalyses as continuous data
Timetoevent data
Timetoevent data can sometimes be analysed as dichotomous data
Hazard ratio
Count data
Counts of common events may often be treated in the same way as continuous outcome data.
Counts of rare events is summarized as rate ratio.
Missing SD
Group means
SD = SE * √N
SD = (√N * [upperlowr limits]) / 3.92
In 90% CI we use 3.29
For small sample size use tvalue
Missing SD
Differences in means
P value [=tinv(pvalue, df)]
SE = MD/ tvalue
SD =
Median and range
Use Median as Mean in case of normal distribution of the data
IQR = 1.35 SD
Combining groups
Dealing with missing data
Learning Objectives
What & Why?
Systematic vs. Literature Review
Overview of Types and Steps of Systematic Review
Defining the review question and developing criteria for including studies
How to search the literature, export results & check duplications [Using Zotero/ Endnote]
How to screen abstracts [Abstrackr/ Covidence]
Construct a Data extraction form
First session
Systematic vs. narrative review
Method of synthesizing evidence ?
The quality of evidence ?
Risk of Bias?
Scope?
Types of Systematic Review
Systematic review of Interventional studies
Systematic review of Observational studies
Systematic review of Diagnostic test accuracy studies
How to perform screening
Using EndNote
Exporting EndNote file to excel sheet
Online software (Abstrackr & Covidence)
Learning Objectives
Second Session
Quality assessment of Included studies
How to construct baseline characteristics table
Generating PRISMA flow diagram and Risk of Bias graph & summary
Standard reporting of Systematic reviews [PRISMA checklist domains]
Tools for ROB assessment
Cochrane ROB tool for RCTs
NOS for Observational studies
ACROBAT NRSI for nonrandomized interventional study
Cochrane ROB tool
Sequence generation (selection bias),
Allocation sequence concealment (selection bias),
Blinding of participants and personnel (performance bias),
Blinding of outcome assessment (detection bias),
Incomplete outcome data (attrition bias),
Selective outcome reporting (reporting bias)
Other potential sources of bias.

Systematically
identify, select, assess, and
synthesize
the relevant body of research, and will help make clear what is
known and not known
about the potential benefits and harms of alternative drugs, devices, and other healthcare services.
Learning Objectives
What & Why?
Systematic vs. Literature Review
Overview of Types and Steps of Systematic Review
Defining the review question and developing criteria for including studies
How to search the literature, export results & check duplications [Using Zotero/ Endnote]
How to screen abstracts [Abstrackr/ Covidence]
Construct a Data extraction form
First session
What & Why?
Systematic vs. Literature Review
Overview of Types and Steps of Systematic Review
Defining the review question and developing criteria for including studies
How to search the literature, export results & check duplications [Using Zotero/ Endnote]
How to screen abstracts [Abstrackr/ Covidence]
Construct a Data extraction form
First session
Learning Objectives
Sources!
Daytoday practice
Textbooks
Online databases
(Uptodata vs. PubMed)
Literature Review
Selection Criteria
Inclusion vs. Exclusion Criteria
Inclusion Criteria domains
1. Population
2. Intervention
3. Comparison
4. Outcomes
5. Study design
How to develop your criteria?
Exporting Results
Practical Workshop
PubMed
CENTRAL
SCOPUS
Importing to EndNote
Exporting as Excel
Remove duplicates
What & Why?
Systematic vs. Literature Review
Overview of Types and Steps of Systematic Review
Defining the review question and developing criteria for including studies
How to search the literature, export results & check duplications [Using Zotero/ Endnote]
How to screen abstracts [Abstrackr/ Covidence]
Construct a Data extraction form
Learning Objectives
Learning Objectives
Third Session
Overview of Basic Statistical Concepts
Introduction to Metaanalysis
Interpretation of forest plot
Choosing statistical method and outcome measure
Pooling continuous and categorical outcomes in metaanalysis model
Assessing and Resolving heterogeneity
Subgroup analysis and Sensitivity analysis
Assessment of Publication bias and interpretation of Funnel plot
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Systematic Review & Metaanalysis of interventional Studies
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