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META -ANALYSIS IN
MEDICAL RESEARCH
Shibila VK
Pharmacy practice
NIPER,Mohali
1
Information about Health Care Is
Everywhere !!!
 But how do you know if one health care
intervention works better than another ?
 Or if it will do more harm than good?
2
Too Much Information !!!
3
There are more than 23,000 medical journals and if
you want to keep up to date, you have to read about
90 journals, in full, every day
Try to remember how you write your review
articles?
4
Narrative reviews
• Most people are highlighting what they like and
what fit their hypothesis
• There is no clearly specified methods of
identifying, selecting, and validating including
information
5
What is a Systematic review?
• Uses explicit preplanned scientific methods to
identify, select, appraise & summarizes similar
but separate studies
All reviews
SR
SR with
MA
6
Knowledge Translation: from Clinical
Research to Practice Decisions
Clinical trial Cochrane Professionals Application
Observational collaboration Societies of policy
Studies
Clinical
policy
(guidelines)
Evidence
synthesis
(SR)
Evidence-
based
healthcare
Knowledge translation 7
Who Is Using Systematic Reviews?
Decision Makers
• Individual doctors and researchers
• Patients and consumers
• Policy makers
8
Steps of a Systematic Reviews
 Frame research question (PICO/PECO)
 Develop protocol
 Develop search strategy
 Run search strategy in at least two databases
 Retrieve and de-duplicate citations
 Develop system for screening titles/abstracts and full-texts
 Screen titles/abstracts
 Retrieve and screen full-texts
 Develop forms for assessing ‘risk of bias’ and extracting data
 Conduct qualitative synthesis( combine the studies)
 Conduct meta-analyses (if appropriate)
 Write report of systematic review
 Update systematic review
9
Frame research question
(PICO/PECO)
Approximate answer to the right question
Vs
Exact answer to the wrong question
Which one is better????
10
11
12
Major databases for RCTs and
observational studies:
 MEDLINE/PubMED
(www.ncbi.nlm.nih.gov/sites/entrez?)
 Cochrane Central Register of Controlled Trials
(CENTRAL)
 EMBASE (www.embase.com)
 SCOPUS
 CTRI
 CINAHL
 PsychINFO
13
Clinical question:
For patients with choroidal neovascularization
associated with age related macular degeneration,
do intra vitreal injections of Lucentis when
compared with Avastin prevent vision loss?
14
To develop simple search
strategy!!!
Break into concepts
P Individuals with choroidal neovascularization associated
with age-related macular degeneration
I Lucentis
C Avastin
O Change in visual acuity or visual field
15
To develop simple search
strategy!!!
Boolean operators
AND, OR, NOT
16
A
N
D
CNV OR
Choroidal
neovascula
risation
Lucentis OR
Avastin
17
`
18
19
Example:
What is the risk of cardiac
arrest in patients taking
H2 receptor blockers
20
Identify keywords
Cardiac arrest
H2 receptor blockers
21
Keyword 1 : Cardiac arrest
Cardiac arrest
Heart attack
(MeSH, TW,TIAB,cardiac*)
22
Key word 2: H2 receptor blocker
H2 receptor blocker
Ranitidine
Famotidine
Cimetidine
(MeSH, TW,TIAB)
23
Screening of Articles:
1. Based on title
2. Based on Abstract
3. Based on full text
24
Reporting guidelines
• PRISMA
(Preferred Reporting Items for Systematic review and
Meta-Analysis)2009 flow diagram.lnk
• MOOSE (Meta-analysis of Observational Studies in
Epidemiology)
25
Data extraction
 Author
 Year
 Study design
 Population
 Male / females
 Sample size
 Diagnostic test
 Intervention
 Outcomes etc.
26
Quality assessment:
1. New castle Ottawa scale NOS.pdf
( For observational studies)
2. Jadad scale (For RCTs)
27
Publication bias:
 Publication bias is a term used when studies
with positive results have a higher likelihood of
being published
 Publication bias can be linked to favorable or
unfavorable treatment of research findings due
to investigators, editors, industry, commercial
interests, or peer reviewers
 A funnel plot–a scatter plot of component
studies
28
29
30
Heterogeneity
 Any kind of variability among studies
 Clinical heterogeneity
Patients, study settings , quality,intervention,outcome
• Statistical heterogeneity
Results of individual trials are not consistent with each
other
( p value for cochrane Q statistics < 0.10
I2 statistic > 50 % )
31
What is a Meta-Analysis?
 Meta-analysis is an optional component of a
systematic review
 “A statistical analysis which combines the results of
several independent studies considered by the
analyst to be ‘combinable”
32
When to do meta-analysis
• More than one study has estimated a treatment effect or
association
• The differences in the study characteristics are unlikely to
affect the treatment effect
• The treatment effect have been measured and reported in
similar ways
33
Analysis
Revman software
CMA
STATA
M.Excel
34
35
Author ,
Year Odds ratio
Confidence
interval
Effect estimate
Effect size
Interpretation of forest plot
 Often, we have 6 columns in a forest plot.
 Column 1: Studies IDs
 Column 2 and column 3: Intervention group n/N and
Control group n/N
 Column 4: Relative risk (fixed) 95% CI
 Column 5: Weight (%)
 Column 6: Relative risk (fixed) 95% CI
same as 4, just in numerical format.
36
Interpretation of forest plot
 The p-value indicates the level of statistical
significance.
 If the diamond shape does not touch the line of no
effect, the difference found between the two groups
was statistically significant.
 In that case, the p-value is usually < 0.05.
37
Forest plot
38
Forest plot
39
THANK YOU

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Meta-analysis in medical research

  • 1. META -ANALYSIS IN MEDICAL RESEARCH Shibila VK Pharmacy practice NIPER,Mohali 1
  • 2. Information about Health Care Is Everywhere !!!  But how do you know if one health care intervention works better than another ?  Or if it will do more harm than good? 2
  • 4. There are more than 23,000 medical journals and if you want to keep up to date, you have to read about 90 journals, in full, every day Try to remember how you write your review articles? 4
  • 5. Narrative reviews • Most people are highlighting what they like and what fit their hypothesis • There is no clearly specified methods of identifying, selecting, and validating including information 5
  • 6. What is a Systematic review? • Uses explicit preplanned scientific methods to identify, select, appraise & summarizes similar but separate studies All reviews SR SR with MA 6
  • 7. Knowledge Translation: from Clinical Research to Practice Decisions Clinical trial Cochrane Professionals Application Observational collaboration Societies of policy Studies Clinical policy (guidelines) Evidence synthesis (SR) Evidence- based healthcare Knowledge translation 7
  • 8. Who Is Using Systematic Reviews? Decision Makers • Individual doctors and researchers • Patients and consumers • Policy makers 8
  • 9. Steps of a Systematic Reviews  Frame research question (PICO/PECO)  Develop protocol  Develop search strategy  Run search strategy in at least two databases  Retrieve and de-duplicate citations  Develop system for screening titles/abstracts and full-texts  Screen titles/abstracts  Retrieve and screen full-texts  Develop forms for assessing ‘risk of bias’ and extracting data  Conduct qualitative synthesis( combine the studies)  Conduct meta-analyses (if appropriate)  Write report of systematic review  Update systematic review 9
  • 10. Frame research question (PICO/PECO) Approximate answer to the right question Vs Exact answer to the wrong question Which one is better???? 10
  • 11. 11
  • 12. 12
  • 13. Major databases for RCTs and observational studies:  MEDLINE/PubMED (www.ncbi.nlm.nih.gov/sites/entrez?)  Cochrane Central Register of Controlled Trials (CENTRAL)  EMBASE (www.embase.com)  SCOPUS  CTRI  CINAHL  PsychINFO 13
  • 14. Clinical question: For patients with choroidal neovascularization associated with age related macular degeneration, do intra vitreal injections of Lucentis when compared with Avastin prevent vision loss? 14
  • 15. To develop simple search strategy!!! Break into concepts P Individuals with choroidal neovascularization associated with age-related macular degeneration I Lucentis C Avastin O Change in visual acuity or visual field 15
  • 16. To develop simple search strategy!!! Boolean operators AND, OR, NOT 16 A N D CNV OR Choroidal neovascula risation Lucentis OR Avastin
  • 17. 17
  • 18. ` 18
  • 19. 19
  • 20. Example: What is the risk of cardiac arrest in patients taking H2 receptor blockers 20
  • 21. Identify keywords Cardiac arrest H2 receptor blockers 21
  • 22. Keyword 1 : Cardiac arrest Cardiac arrest Heart attack (MeSH, TW,TIAB,cardiac*) 22
  • 23. Key word 2: H2 receptor blocker H2 receptor blocker Ranitidine Famotidine Cimetidine (MeSH, TW,TIAB) 23
  • 24. Screening of Articles: 1. Based on title 2. Based on Abstract 3. Based on full text 24
  • 25. Reporting guidelines • PRISMA (Preferred Reporting Items for Systematic review and Meta-Analysis)2009 flow diagram.lnk • MOOSE (Meta-analysis of Observational Studies in Epidemiology) 25
  • 26. Data extraction  Author  Year  Study design  Population  Male / females  Sample size  Diagnostic test  Intervention  Outcomes etc. 26
  • 27. Quality assessment: 1. New castle Ottawa scale NOS.pdf ( For observational studies) 2. Jadad scale (For RCTs) 27
  • 28. Publication bias:  Publication bias is a term used when studies with positive results have a higher likelihood of being published  Publication bias can be linked to favorable or unfavorable treatment of research findings due to investigators, editors, industry, commercial interests, or peer reviewers  A funnel plot–a scatter plot of component studies 28
  • 29. 29
  • 30. 30
  • 31. Heterogeneity  Any kind of variability among studies  Clinical heterogeneity Patients, study settings , quality,intervention,outcome • Statistical heterogeneity Results of individual trials are not consistent with each other ( p value for cochrane Q statistics < 0.10 I2 statistic > 50 % ) 31
  • 32. What is a Meta-Analysis?  Meta-analysis is an optional component of a systematic review  “A statistical analysis which combines the results of several independent studies considered by the analyst to be ‘combinable” 32
  • 33. When to do meta-analysis • More than one study has estimated a treatment effect or association • The differences in the study characteristics are unlikely to affect the treatment effect • The treatment effect have been measured and reported in similar ways 33
  • 35. 35 Author , Year Odds ratio Confidence interval Effect estimate Effect size
  • 36. Interpretation of forest plot  Often, we have 6 columns in a forest plot.  Column 1: Studies IDs  Column 2 and column 3: Intervention group n/N and Control group n/N  Column 4: Relative risk (fixed) 95% CI  Column 5: Weight (%)  Column 6: Relative risk (fixed) 95% CI same as 4, just in numerical format. 36
  • 37. Interpretation of forest plot  The p-value indicates the level of statistical significance.  If the diamond shape does not touch the line of no effect, the difference found between the two groups was statistically significant.  In that case, the p-value is usually < 0.05. 37

Editor's Notes

  1. Inevitably, studies brought together in a systematic review will differ. Any kind of variability among studies in a systematic review may be termed heterogeneity. It can be helpful to distinguish between different types of heterogeneity. Variability in the participants, interventions and outcomes studied may be described as clinical diversity (sometimes called clinical heterogeneity), and variability in study design and risk of bias may be described as methodological diversity (sometimes called methodological heterogeneity). Variability in the intervention effects being evaluated in the different studies is known as statistical heterogeneity, and is a consequence of clinical or methodological diversity, or both, among the studies. Statistical heterogeneity manifests itself in the observed intervention effects being more different from each other than one would expect due to random error (chance) alone. We will follow convention and refer to statistical heterogeneity simply as heterogeneity.