1. HS 4160 Critical Scientific Analysis
Week 2: Array CGH in patients with learning disability (mental retardation) and congenital anomalies: updated systematic review and meta-analysis of 19 studies and 13,926 subjects
HS 4160 Critical Scientific Analysis

2. Objectives Compare meta-analysis with narrative review.
Discuss the use of tables in systematic review and meta-analysis paper.
Review types of table used in systematic review and meta-analysis paper.
Define elements of table.
Assess quality of tables.
Critically assess the tables of the provided meta-analysis.

3. Research Design

4. Highest form of Research Design:
Case-control Studies
Randomized Controlled Trials
Systematic Reviews
Expert Opinions

5. Which of the following is a prospective study?
Case-control Study
Cohort Study
Randomized Controlled Trial
Expert Opinions

6. Systematic Review & Meta-analysis
Exhaustive exploration, critical evaluation and synthesis of all the unbiased evidence
Meta-analysis
Exhaustive exploration, critical evaluation and quantitative synthesis of all the unbiased evidence
Combination of the results of a number of related randomised trials

7. Systematic Review & Meta-analysis
(Overview)
Extract data from published reports
Collect summary data
Collect individual patient data (IPD)
….So not all meta-analyses are the same.
This diagram represents a continuum of quality of approach to meta-analysis.
...As I said already there are meta-analyses that are not derived from a systematic review.
.... There are those that are based on data extracted from the published trials and this is dependent on what trial are published and what is available in published reports. ….
...A better approach is to collect summary data on all (not just published trials) and obtain extra data from the trial investigators where necessary
...The final approach is to collect individual patient data from the original trial investigators and re-analysing the results…This is the method we use, and this is the path the we follow…Syst Rev and meta-analysis of IPD.

8. Using unbiased evidence Statistical analysis Exhaustive exploration
Which of the following is not in common between meta-analysis and systematic review?
Using unbiased evidence
Statistical analysis
Exhaustive exploration
Critical evaluation

9. Meta-analysis:
Meta-analysis is a statistical analysis of a collection of studies
Meta-analysis methods focus on contrasting and comparing results from different studies in anticipation of identifying consistent patterns and sources of disagreements among these results

10. Features of narrative reviews and systematic reviews
NARRATIVE SYSTEMATIC
QUESTION Broad Focused
SOURCES/ Usually unspecified Comprehensive; SEARCH Possibly biased explicit
SELECTION Unspecified; biased? Criterion-based;
uniformly applied
APPRAISAL Variable Rigorous
SYNTHESIS Usually qualitative Quantitative
INFERENCE Sometimes Usually evidence-
evidence-based based

11. Array-Based Comparative Genomic Hybridization (a-CGH)

12. Oligo aCGH Plateform oligonucleotide in situ synthesis process
oligonucleotide probes
via inkjet printing

13. aCGH Procedure Test tissue Control tissue DNA extraction Test DNA
Control DNA
DNA enzyme digestion
Label with fluorescent dye Cy5
Label with fluorescent dye Cy3
Clean to get rid of excess fluorescent dye
Mix
Load to array slide
Hybridization
Post washing

14. aCGH Procedure
Scan array slide with scanner

16. Agilent Genomics Workbench 5.0
Log fluorescence intensity ratio between test DNA to control DNA
test DNA fluorescence intensity
= log
control DNA fluorescence intensity
Between -1 and +1:
no gain and no deletion
>+1: gain one extra copy
>+2: gain two extra copy
<-1: one copy deletion
<-2: two copy deletion

17. Array Data Analysis
deletion
Gain
Gene copy
number change

18. Objective(s) of a study could usually be found under ____ of a meta-analysis?
abstract
introduction
methods
a & b
a, b, & c

19. abstract introduction methods a & b a, b, & c
Detail inclusion/exclusion criteria could usually be found under ___ of a meta-analysis?
abstract
introduction
methods
a & b
a, b, & c

20. abstract introduction methods a & b a, b, & c
Detail statistical analysis could usually be found under ___ of a meta-analysis?
abstract
introduction
methods
a & b
a, b, & c

21. How to read a table

22. How to read a table

23. How to read a table

24. How to read a forest plot

25. The solid black boxes from the graph represent
Individual study results
Pooled study results
Confidence interval
None of the above

26. The diamond from the graph represent
Individual study results
Pooled study results
Confidence interval
None of the above

27. The pooled effect from the graph in previous slide is significant
True
False

28. How to read a forest plot