1 HS 4160 Critical Scientific AnalysisWeek 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-analysisExhaustive 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 reviewsNARRATIVE 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 processoligonucleotide probes via inkjet printing

13 aCGH Procedure Test tissue Control tissue DNA extraction Test DNAControl 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

15

16 Agilent Genomics Workbench 5.0Log 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, & cDetail 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, & cDetail 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 representIndividual study results Pooled study results Confidence interval None of the above

26 The diamond from the graph representIndividual study results Pooled study results Confidence interval None of the above

27 The pooled effect from the graph in previous slide is significantTrue False

28 How to read a forest plot