Systematic Review & Meta Analysis

Question 1

Hierarchy of Evidence (9)

- ideas, editorials, opinions

Answer 1

1. Systematic reviews & meta analysis
2. Randomised controlled double-blind trials
3. Cohort studies
4. Case-control studies
5. Case series
6. Case report
7. Ideas, editorials, opinions
8. Animal research
9. In-vitro (test tube) research

Question 2

Systematic review definition (4)

Answer 2

• a clearly formulated question
• uses systematic & explicit methods to identify, select & critically appraise relevant research
• to collect & analyse data from the studies that are included in the review
• may or may not use statistical methods to analyse & summarise the results (meta-analysis)

Question 3

Meta analysis

Answer 3

• use statistical techniques to integrate the results of several independent studies into a single quantitative estimate or summary effect size

Question 4

Difference between Narrative Review & Systematic Review

1. Question
2. Sources & search
3. Selection of independent studies
4. Appraisal
5. Synthesis of data

Answer 4

Narrative Review

1. Question
   - broad in scope
2. Sources & search
   - not specified
   - potentially bias
3. Selection of independent studies
   - not specified
   - potentially bias
4. Appraisal
   - variable
5. Synthesis of data
   - often a qualitative summary

Systematic Review

1. Question
   - focused clinical question
2. Sources & search
   - comprehensive sources & explicit search strategy
3. Selection
   - uniform criterion-based selection
4. Appraisal
   - rigorous critical appraisal
5. Synthesis of data
   - may or may not include meta-analysis

Question 5

Purpose of Meta analysis (4)

Answer 5

1. Increase statistical power
2. Improve precision
   - increase sample size leads to narrower 95% CI
3. Settle controversies arising from apparently conflicting studies or to generate new hypothesis
4. Answer questions not posed by the individual studies

Question 6

Relevance of systematic review to pharmacy practice (2)

Answer 6

1. Development of evidence-based practice guidelines
2. Economic evaluations in healthcare
   - generate clinical policies to optimise outcomes using available resources
   eg cost-effectiveness

Question 7

**
Steps in conducting systematic review
- with or without meta analysis

(6)

Answer 7

• *
  1. Formulate the review question & develop the systematic review protocol
  2. Search the literature
• search strategy
• study selection
  3. Assess quality of study
  4. Abstract data
  5. Analyse data (may include meta analysis) & interpret results
• heterogeneity among studies (clinical, methodological & statistical)
• publication bias
  6. Report findings

Question 8

How to formulate the review question?

Answer 8

• use PICO approach

Population
Intervention
Comparison
Outcome

Question 9

Develop the systematic review protocol

- criteria to selection of studies

Answer 9

• define the study selection criteria (inclusion & exclusion criteria)

Question 10

Inclusion / exclusion criteria

Answer 10

• type of study design
• type of population
• type of intervention
• type of comparison
• type of outcome
  (( PICO ))

Question 11

Search strategy

Answer 11

• conduct comprehensive literature search
  eg multiple electronic databases or hand searching of reference lists of publications
• formulate search terms for electronic search

Question 12

Examples of multiple electronic databases (3)

Answer 12

1. PubMed
2. Embase
3. Cochrane Central Register of Controlled Trials

Question 13

Study selection process (4)

Answer 13

• based on pre-defined study selection criteria
• record the number of studies included & excluded at each step & reason for exclusion
• at least 2 independent reviewers to select studies
• any discrepancies between reviewers to be resolved through discussion or third investigator

Question 14

Assess quality of study (3)

Answer 14

• at least 2 independent reviewers to be involved
• any discrepancies between reviewers to be resolved through discussion or third investigator
• 3 types

Question 15

Types of scale to assess quality of study (2+1)

Answer 15

For RCT

1. Jaded scale
2. Cochrane risk-of-bias tool ver 2

For observational studies
1. Newcastle-Ottawa Scale (NOS)

Question 16

Jaded scale (2)

Answer 16

• RCT
• score range from 0-5
• low (0-2), high (3-5)

Question 17

Disadvantage of Jaded scale

Answer 17

• score cannot tell which part of the study is lacking unless table is reported

Question 18

Cochrane RoB tool ver 2 (2)

Answer 18

• RCT

- domain based (low risk of bias, some concern & high risk of bias)

Question 19

Newcastle-Ottawa Scale (NOS)

Answer 19

• observational studies (specifically case-control & cohort studies)

Question 20

NOS for case-control studies

• selection
• comparability
• ascertainment

Answer 20

• selection of cases & controls
• comparability of cases & control
• ascertainment of exposure

Question 21

NOS for cohort studies

• selection
• comparability
• ascertainment

Answer 21

• selection of exposed & unexposed
• comparability of exposed & unexposed
• ascertainment of outcome

Question 22

Abstract data

Answer 22

• develop a standardised data abstraction form
• at least 2 reviewers to abstract information from studies independently
• any discrepancies between reviewers to be resolved through discussion or third investigator

Question 23

Methods to reduce discrepancies in

• study selection
• assessment of study quality
• abstract data

(2)

Answer 23

• discussion between reviewers until consensus is reached

- invite third investigator for review & resolution

Question 24

Types of analysis of data (2)

Answer 24

1. Qualitative data synthesis

2. Quantitative data synthesis

Question 25

Qualitative data synthesis

Answer 25

- tabulation / graphical display of characteristics & results of individual studies

Question 26

Quantitative data synthesis & uses (3)

Answer 26

``` - use statistical software eg Sata, RevMan - examine heterogeneity among studies eg Forest plot - assess for publication biass eg Funnel plot ```

Question 27

Forest plot - square (midpoint) - line - size of square - diamond (midpoint) - width of diamond

Answer 27

- each tree (line) represents a study - square is the point estimate - size of square is weight of the study - horizontal line is 95% CI - mid-point of diamond is summary effect measure - width of diamond is 95% CI of summary measure

Question 28

Weight of the study

Answer 28

= (1 / variance) - large sample size, smaller variance, larger weight - small sample size, larger variance, smaller weight

Question 29

Types of heterogeneity among studies (3) | & its stratification

Answer 29

1. Clinical heterogeneity - clinical relevance eg doses, duration of treatment, population type, method of measuring outcome 2. Methodological heterogeneity - study design & quality eg case-control, cohort, RCT 3. Statistical heterogeneity - statistical methods

Question 30

Statistical heterogeneity among studies

Question 31

How to assess for statistical heterogeneity among studies (2)

Answer 31

1. Cochran's Q test | 2. I^2 statistic

Question 32

Cochran's Q test

Answer 32

- chi square test | - statistically significant heterogeneity if p<0.1

Question 33

I^2 statistic

Answer 33

- proportion of total variance due to between study variability - in terms of % - increasing value means increasing heterogeneity = (between study variability/total variance) x 100%

Question 34

If there is statistical significant heterogeneity among studies, what model to use? (2)

Answer 34

- use random-effects model | - to account for variability between studies

Question 35

If there is no statistical significant heterogeneity among studies, what model to use? (1)

Answer 35

- use fixed-effects model

Question 36

Assessment for publication bias (2)

Answer 36

- use funnel plot | - Egger's test for funnel plot asymmetry, asymmetry if p<0.05 suggesting presence of bias

Question 37

What type of analysis is prone to publication bias? | Why? (2)

Answer 37

Meta analysis because : - studies with negative results are less likely to be published & mainly positive results are published & hence used in systemic review - hence, results from meta-analysis may overstate a treatment effect (or reduce impact of exposure)

Question 38

Funnel plot - x & y axis - description of plot (4) (6)

Answer 38

- y axis : size of study or precision/standard error - x axis : effect measure eg risk ratio, odds ratio - smaller study have wider scatter of effect estimate (bottom of pyramid) - larger study have narrower scatter of effect estimate (top of pyramid) - top of pyramid is the line of symmetry - slope of both sides of the pyramid is 95% CI of overall effect estimate

Question 39

``` ** Report findings (4) ```

Answer 39

** - summarise key findings - judge validity of findings eg poor quality studies can recommend to disregard - judge for generalisability - implications for further studies or clinical practice

Question 40

Reporting format for systematic reviews & meta analysis (2)

Answer 40

1. PRISMA statement | 2. MOOSE guidelines

Question 41

PRISMA statement

Answer 41

Preferred Reporting Items for Systematic reviews & Meta Analysis

Question 42

MOOSE guidelines

Answer 42

Meta analysis Of Observational Studies in Epidemiology

Question 43

Reporting guidelines - observational studies - systematic review & meta analysis

Answer 43

Observational studies - STROBE (STrengthening the Reporting of OBservational studies & Epidemeoogy) Systematic review & meta analysis - PRISMA (Preferred Reporting Items for Systematic reviews & Meta Analyses) - MOOSE (Meta analysis Of Observational Studies & Epidemiology)