15

15.1
(review articles)
2 (Narrative review)(1)
(original articles)

(Systematic reviews)(2)
original articles
(Clinical trials)
(Randomized controlled trials, RCT)
(3)
RCT

Meta-analysis(4) meta-analysis
systematic reviews

15.1
15.1
15.2
15.3 Meta-analysis
15.4

 15.1 (5)




1 5 . 1 . 1
(Publication biases)

(6)
negative result

15.1.2 (Citation
biases)

(7)

15.1.3

15.1.4

f 210 e

15.2
(Systematic review)
Archie Cochrane

(RCT)
.. 1972(8)

RCT


RCT

Systematic review

Cochrane collaboration( 9 )

Cochrane database of systematic reviews

RCT
1985(10)



RCT




RCT(11)

(.. 2553)
RCT 530,000 (12)
RCT
Systematic review

15.2.1

5


(study design) PICOS
P = Participant ()

I = Intervention ( )
(efficacy)

C = Comparison ( )
(placebo)
(control group)

O = Outcome ( )

S = Study design ()

(blinded RCT)

f 211 e

15.2.2
(review protocol)

( 3-8)
Cochrane collaboration

Cochrane review group
(peer review)




Cochrane review group
Cochrane library

15.2.3

(criteria)
( RCT )

( 15.1)
4
(Publication bias)(6)
y
MEDLINE, EMBASE,
(Cochrane controlled
trials register)(12),

y


MEDLINE

y



y

Thai index medicus

15.1
MEDLINE snake bites(13)
set
001
002
003
004
005
006
007
008
009
010
011
012
013
014
015
016
017
018
019
020
021
022
023
024
025
026
027
028

Search
exp snake bites/
randomized controlled trial.pt.
randomized controlled trials/
controlled clinical trial.pt.
random allocation
double blind method/
single blind method/
or/2-7
clinical trial.pt.
exp clinical trials/
(clin$ adj25 trial$).tw.
((singl$ or doubl$ or trebl$ or tripl$) adj25
(blind$ or mask$)
placebos/
placebo$.tw.
random$.tw.
research design/
or/9-16
comparative study/
exp evaluation studies/
follow up studies
prospective studies
(control$ of prospectiv$ or volunteer$).tw.
or/18-22
animal/not (human/ and animal/)
8 or 17 or 23
25 not 24
1 and 26
27

f 212 e

15.2.4

(inclusion criteria)

inclusion criteria

PICOS,

(uncontrolled studies)
(non-randomized
studies)



15.2.5
(14)
2

(intervention
group) (control
group)
(placebo)
(15)
. (randomization)


(Selection bias)
(concealment
of allocation)
.

(Performance bias)
.
(blinded outcome assessment)


(Detection bias)
.

(intent to treat analysis)

(Attrition bias)

(16)

1 5 . 2 . 6 (data
extraction)

RCT

( 15.2)

RCT

f 213 e

 RCT
meta-analysis

15.2.7 (Metaanalysis)
RCT


(inclusion criteria)
(case definition)
(study
design)
Meta-analysis ()
15.2.8

(implication to practice)
(implication to research)

Cochrane review group
peer review



(Cochrane library)


Preferred Reporting
Items for Systematic Reviews and Meta-Analyses(17)
(PRISMA, 15.2)
3

15.2 meta-analysis PRISMA(17)

TITLE
Title
ABSTRACT
Structured
summary
INTRODUCTION
Rationale
Objectives
METHODS
Protocol and
registration
Eligibility criteria

systematic review, meta-analysis .

background; objectives; data sources; study eligibility criteria,

participants, and interventions; study appraisal and synthesis methods; results; limitations;
conclusions and implications of key findings; systematic review registration number.

3
4

(PICOS).

(review protocol)

( PICOS, )
( )
(
)

Information sources

Search

Study selection

f 214 e

Data collection
process
Data items

10

Risk of bias in
individual studies

12

Summary measures
Synthesis of results

13
14

Risk of bias across

studies
Additional analyses

15

RESULTS
Study selection

11

16

17

Study
characteristics
Risk of bias within
studies
Results of individual
studies

18

Synthesis of results

21

Risk of bias across

studies
Additional analysis

22

19
20

meta-analysis)
(
)
( PICOS, )

(
),

( risk ratio, difference in means).

( I2) meta-analysis.
(
)
( metaregression)



( PICOS,
)

( 12)


forest plot.
meta-analysis

( 15)

23

( metaregression) 16

DISCUSSION
Summary of
evidence

24

Limitations

25

Conclusions

26

(
)
( ),
( )

FUNDING
Funding

27

(
)
f 215 e


Cochrane collaboration

(18)

(clinical
practice guidelines)

5676

Cochrane database of systematic review(12)
3
CD-ROM The Cochrane Library
World Wide Web (http:/www.cochrane.org)

RCT

RCT

qualitative review ( 15.1)
RCT

(a priori hypothesis)
(proposal)

Cochrane
collaboration
(peer
reviewed)

(post-hoc analysis)

15.3 Meta-analysis

Meta-analysis(19,20)

(weighted average)

Meta-analysis
meta-analysis

Metaanalysis


Meta-analysis

Meta-analysis (20)
meta-analysis

15.3.1 Mean estimate of treatment effect

intervention odds
ratio (OR, 15.2) relative risk (RR,
15.2) (outcome)
(treatment group)
(placebo group)
()

f 216 e

 (OR or RR <1.0)
RR
Meta-analysis
odds ratio

(robust statistics)
15.3.2 Confidence interval (CI)
95% OR


1.0
meta-analysis
OR < 1.0
CI
1.0

Forest plot
95%

95%

95%

95%

Forest plot
OR RR = 1
(no effect line)
( )
OR RR <1


OR RR > 1

15.2 Forest plot (intervention) (placebo)

(control group) ,
#

f 217 e


( 15.3, 15.4)
odds ratio,
relative risk, risk difference

(weighted mean difference) standardized mean
difference
odds ratio

15.3 meta- analysis20

(treatment)
(exposure)
(treatment group)
(control group)

(event)
A
C
A+C

(no event)
B
D
B+D

A+B
C+D
N

OR

Odds ratio

(A / B)
(C / D)

RR

Relative risk

(A / (A + B))
(C / (C + D))

RR reduction

ARR

Absolute risk reduction =

(A / (A+B)) (C / (C+D))

NNT, Number needed to treat = 1 / ARR

Peto Odds ratio, PetoORi =

1 RR

O E
exp i i
Vi

(21) ( 15.3)
Fixed effect model
(true effect)



(result)
(random error)

(inverse variance

1/variance)
- (15.3)

Random effect model ( 15.3)

(trial specific effect)

(true

f 218 e

mean effect)
(
15.4)

Review Manager (Revman) 5.0
Peto odds

ratio 95% odds ratio

forest plot
meta-analysis
meta-analysis SAS version 9

15.4 meta- analysis(20)

Summary

Statistics
Model

Odds ratio (O-E)
Fixed effect
(Dichotomous)
Random effect
Relative risk
Fixed effect
Random effect
Risk difference
Fixed effect
Random effect

Weighted mean
Fixed effect
(Continuous)
difference
Random effect
Standardized mean
Fixed effect
difference
Random effect

Odds ratio (O-E)

(Individual patient data)

Method
Peto, Mantel-Haenszel
DerSimonian & Laird
Mantel-Haenszel
DerSimonian & Laird
Mantel-Haenszel
DerSimonian & Laird
Inverse variance
DerSimonian & Laird
Inverse variance
DerSimonian & Laird

15.3 Meta-analysis (21)

f 219 e

Peto

1 5 . 3 . 3
(Homogeneity test)

OR CI

homogeneity test(20)

Cochrans Q test
2
(homogenous)
Q
( heterogeneity)

I2 index(22)
(variability)

I2 index = 0%

I2 index = 50%
(heterogeneity)

heterogeneity

(20)

( )


stratification heterogeneity

meta-regression(23)
15.3.4 (Subgroup
analysis)(20)

(Subgroup)



meta-analysis

a priori hypothesis

(post-hoc analysis)

f 220 e

15.3.5 Sensitivity analysis(20) metaanalysis

15.4 Funnel plot (study weight or sample size)

(odds ratio) meta-analysis,

odds ratio 1
1 5 . 3 . 6
(Publication biases)

(24) Funnel plot
( 15.4) scattergram
risk ratio
risk ratio

risk ratio

risk ratio

(25)

scattergram

(1/SE)

15.4

Meta-analysis

(26)


Meta-analysis

f 221 e


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