This presentation is the second part from Ahmed Negida's course titled: Systematic review and Meta-analysis.

1. Systematic review and Meta-analysis
PART 2
Ahmed Said Negida
Fourth year (MBBCH) student at Zagazig University
Leader of Medical Research Group of Egypt (MRGE)
Clinical Research Assistant at Egyptian Liver Research Institute and Hospital
Head of scientific committee of the Student Research Unit, Zagazig University

2. Learning objectives
 Quality assessment (ROB assessment tool).
 Baseline characteristics tables.
 Figures of (PRISMA flow diagram, ROB summary and ROB graph).
 PRISMA checklist.
 Introduction to Meta-analysis.

3. Quality assessment (ROB assessment tool).
 Cochrane ROB tool is used to assess the quality randomized controlled trials.
 For observational studies (use STROBE or NOS instead).
 For non-randomized studies (Use ACROBAT NRSI tool).

4. Components of Cochrane ROB tool
1. Sequence generation
2. Allocation concealment
3. Blinding
4. Incomplete outcome data
5. Selective outcome reporting
6. Others
HIGH risk
LOW risk
Unclear

5. 1. Sequence generation
Low RISK HIGH RISK
1- Computer generated
2- Randomization tables
3- Block randomization
4- Minimization procedure
1- Quasi-random
2- Patient preference
3- clinician judgment
4- Day of visit
5- Patient ID
6- Day of birth

6. 2. Allocation concealment
Low RISK HIGH RISK
1- Central Allocation
2- Opaque envelop
3- Sealed envelop
4- Allocators were blinded
5- Identical drug containers
1- Transparent envelop
2- Allocators were not blinded
3- Random sequence known in
advance

7. 3. Blinding
Low RISK HIGH RISK
1- Patients and study personnel
were blinded to ttt groups.
2- They were not blinded but this
is not likely to affect the
outcome.
1- Open label study
2- No placebo group
“observation group”.

8. 4. Incomplete outcome data
Low RISK HIGH RISK
1- No missing outcome data
2- Missing are not related to true
outcome. “survival outcome”
3- Missing outcome data balanced in
numbers across intervention groups.
4- Missing data were handled by ITT.
1- missing data >5%-10%
2- Missing data were not
handled with appropriate
analysis.

9. 5. Selective outcome reporting
Low RISK HIGH RISK
1- All pre-specified outcomes in
the protocol were reported.
2- Protocol was not available but
it is expected that all major
outcomes are reported.
1- One or more of the pre-
specified outcomes is not
reported. “or reported on
different scales”
2- One or more of the reported
outcomes was not planned.

10. 6. Other sources of bias
Low RISK HIGH RISK
The study is free from other
sources of bias.
1- Stopped early due to some
data-dependent process.
2- Had extreme baseline
imbalance.
3- Had some other problem (….)

11. How to generate ROB graphs in RevMan
(1) Add eligible studies from
references to included studies.

12. (2) From “tables”,
open
“characteristics of
included studies”.

13. (3) Select
author
judgment for
each of the
ROB domains.

14. (4) Add Figure.
(5) Choose:-
Risk of Bias Graph
Then, Risk of Bias
Summary.

15. Baseline characteristics tables
 Importance of baseline characteristics
 Describe population in the starting point.
 Effect size (SMD) = (End point/SD – Starting point/SD)
 To detect between group differences.
 How baseline characteristics are presented
Usually, they are the first table in the “Results” section.
 Type of variables presented
1. Continuous
2. Categorical

16. 1. Continuous variables
e.g. Age, Weight, Height, BMI, UPDRS
 Mean (SD)
 Median (IQR)

17. 2. Categorical variables
e.g. Gender, grade,…
 Frequency (Percentage)

18. REFERENCE:
Mingrone, Geltrude, et al.
"Bariatric surgery versus
conventional medical therapy
for type 2 diabetes." New
England Journal of Medicine
366.17 (2012): 1577-1585.

19. Reference:
Venturelli, Massimo, Renato Scarsini, and
Federico Schena. "Six-month walking
program changes cognitive and ADL
performance in patients with Alzheimer."
American journal of Alzheimer's disease
and other dementias 26.5 (2011): 381-388.

20. Reference
Klop, Karel WJ, et al. "Can right‐sided
hand‐assisted retroperitoneoscopic donor
nephrectomy be advocated above
standard laparoscopic donor
nephrectomy: a randomized pilot study."
Transplant International 27.2 (2014): 162-169.

21.  Identify the (most important & commonly reported) variables within
baseline characteristics table of included studies.
 Present each study as (one, two, or more…) rows.
 Each row represents a group within a study. For example: If you
have a four arm trial, this will be presented in four rows.
 Present variables as columns.
How to format the baseline characteristics table of a systematic review

22. How to format the baseline characteristics table of a systematic review
GROUP 1 GROUP 2
GROUP 1
GROUP 2
GROUP 1
GROUP 2
V1
V2
V3
V1 V2 V3
Table of an individual study Table of a systematic review

23. EXAMPLE 1

24. EXAMPLE 2

25. PRISMA
checklist
TITLE Risk of bias across studies
ABSTRACT Additional analyses
Structured summary RESULTS
INTRODUCTION Study selection
Rationale Study characteristics
Objectives Risk of bias within studies
METHODS Results of individual studies
Protocol and registration Synthesis of results
Eligibility criteria Risk of bias across studies
Information sources Additional analysis
Search DISCUSSION
Study selection Summary of evidence
Data collection process Limitations
Data items Conclusions
Risk of bias in individual studies FUNDING
Summary measures Risk of bias across studies
Synthesis of results

26. Introduction to Meta-analysis
Meta-analysis is a statistical method for quantitative
evidence synthesis in which eligible studies are pooled
together in the meta-analysis model to give an overall
effect size with a greater power.

27. Introduction to Meta-analysis
 Advantages ??
 Disadvantages ??
 Idea of meta-analysis ??

28. Effect size
Mean difference (MD) X – Y
Standardized Mean Difference (SMD) (X – Y) / SD
Risk Ratio (RR) X / Y
Risk Difference X – Y
Odds Ratio X / Y
from a case control study
 For continuous outcomes
 For categorical outcomes
 Others: e.g. Hazard Ratio (HR)

29. Random effect model vs. Fixed effect model
 Study weights are more balanced under the random-effects
model than under the fixed-effect model. Large studies are
assigned less relative weight and small studies are assigned
more relative weight as compared with the fixed-effect model.
 The standard error of the summary effect and (it follows) the
confidence intervals for the summary effect are wider under the
random-effects model than under the fixed-effect model.

30. Interpretation of forest plots
The following forest plots shows the standardized mean difference of
hospital stay after Holmium Laser Enucleation of Prostate in
comparison to Transurethral resection of prostate:

31. The following forest plots shows the standardized mean difference of
change in HBa1c in Gastric Bypass surgery versus Medical Therapy:

32. The following forest plots shows the standardized mean difference
of change in BMI in Gastric Bypass surgery versus Medical Therapy:

33. The following forest plots shows the standardized mean difference
of change in total UPDRS score in Coenzyme Q10 group vs.
placebo group:
NB: pooled studies are heterogeneous