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Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group [email protected] Workshop systematic reviews Leuven June 4-6, 2012 Introduction to meta-analysis

Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group [email protected] Workshop systematic reviews

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Page 1: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium

Belgian Campbell [email protected]

Workshop systematic reviews Leuven June 4-6, 2012

Introduction to meta-analysis

Page 2: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

1. Introducing meta-analysis for group designed studies

2. Effect sizes3. Meta-analysis of studies with other designs

Content

Page 3: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

1. Introducing meta-analysis

Page 4: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

The role of chance

Example: association between gender and math

M = 8 ; F = 8.5 ; M = F = 1.5

F M

0.33

M F

Page 5: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

Standardized mean difference (Cohen, 1969):

Estimated by its sample counterpart:

A B

A B

p

X Xg

S

‘True’ effect size

‘Observed’ effect size

0.20 = small effect

0.50 = moderate effect

0.80 = large effect

Page 6: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

sM sF p (2-sided) g

8.10 9.34 1.55 1.55 0.015 (*) 0.80

MxFx

Example: M = 8 ; F = 8.5 ; M = F = 1.5 => δ = 0.33

nM=nF = 20

Page 7: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

sM sF p (2-sided) g

8.107.60

9.347.59

1.551.23

1.551.47

0.015 (*)0.98

0.80-0.0069

MxFx

Example: M = 8 ; F = 8.5 ; M = F = 1.5 => δ = 0.33

Page 8: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

sM sF p (2-sided) g

8.107.607.967.708.177.868.198.117.868.34

9.347.598.818.258.258.817.938.157.948.53

1.551.231.381.491.761.241.791.761.891.39

1.551.471.591.651.331.581.781.971.641.79

0.015 (*)0.980.0780.280.870.040 (*)0.650.950.890.71

0.80-0.00690.570.350.0530.67-0.140.0200.0420.12

MxFx

Example: M = 8 ; F = 8.5 ; M = F = 1.5 => δ = 0.33

Page 9: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

2( )~ ( , )gg N 2

( )

4gwith

N

δ g

Page 10: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

~ ( , 0.1)g N

95 % confidence interval:

1.96 0.1 ; 1.96 0.1g g

Page 11: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

1 2 3 4 5 6 7 8 9 10-1

-0.5

0

0.5

1

1.5

Data set

g

Page 12: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

Suppose simulated data are data from 10 studies, being replications of each other:

Vote-counting procedure?

Combining study results in a meta-analysis

Page 13: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

gg

k

Combining study results in a meta-analysis

Suppose simulated data are data from 10 studies, being replications of each other:

2( ) 0.01g

0.25

2( )~ ( , )gg Nk

Page 14: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

1 2 3 4 5 6 7 8 9 10-1

-0.5

0

0.5

1

1.5

Data set

g

Page 15: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

1. Observed effect sizes may be positive, negative, small, moderate and large.

2. CI relatively large3. 0 often included in confidence intervals

4. Combined effect size close to population effect size (averaging out the noise)

5. CI relatively small (higher accuracy)6. 0 not included in confidence interval (higher

power)

Comparing individual study results and combined study results

Page 16: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

Meta-analysis: Gene Glass (Educational Researcher, 1976, p.3):

“Meta-analysis refers to the analysis of analyses”

Page 17: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

A meta-analysis with dissimilar study sample sizes

2( )~ ( , )gg N 2

( )

4gwith

N

δ g

nM = nF = 100

δ g

nM = nF = 20

Page 18: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

ˆ j

k

g

j j

j

gww

2( )

1

j

j j

jg

with w N

or w

Page 19: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

An example in education(Raudenbush, S. W. (1984). Magnitude of teacher expectancy effects on pupil IQ as a function of the credibility of expectancy induction: A synthesis of findings from 18 experiments. Journal of Educational Psychology, 76, 85-97.)

StudyWeeks prior

contact gj

1.2.3.4.5.6.7.8.9.

10.11.12.13.14.15.16.17.18.19.

Rosenthal et al. (1974)Conn et al. (1968)Jose & Cody (1971)Pellegrini & Hicks (1972)Pellegrini & Hicks (1972)Evans & Rosenthal (1969)Fielder et al. (1971)Claiborn (1969)Kester & Letchworth (1972)Maxwell (1970)Carter (1970)Flowers (1966)Keshock (1970)Henrickson (1970)Fine (1972)Greiger (1970)Rosenthal & Jacobson (1968)Fleming & Anttonen (1971)Ginsburg (1970)

2330033301001233123

0.030.12

-0.141.180.26

-0.06-0.02-0.320.270.800.540.18

-0.020.23

-0.18-0.060.300.07

-0.07

0.130.150.170.370.370.100.100.220.160.250.300.220.290.290.160.170.140.090.17

( )jg

Page 20: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

Mean effect: 0.060, p= .10

Page 21: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

(Keren, R., & Chan, E. (2002). A meta-analysis of randomized, controlled trials comparing short- and long-course antibiotic therapy for urinary tract infections in children. Pediatrics, 109, e70.)

An example in medical research

Study Year Sample Size

RR (95% CI)

Bailey and Abbott 1978 10 1.33 (0.17–10.25)

Khan et al 1981 16 0.20 (0.01–3.61)

Stahl et al 1984 26 1.20 (0.34–4.28)

Fine and Jacobson 1985 31 2.34 (0.53–10.30)

Gaudreault et al 1992 40 1.00 (0.02–48.09)

Pitt et al 1982 42 2.50 (0.11–58.06)

Helin 1984 43 2.53 (0.25–25.81)

Grimwood et al 1988 45 2.80 (0.65–12.02)

Avner et al 1983 49 4.69 (1.13–19.51)

Lohr et al 1981 50 1.28 (0.23–7.00)

Nolan et al 1989 90 10.45 (1.40–78.31)

Copenhagen 1991 264 1.50 (0.68–3.32)

Page 22: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

Note:

treatment failure in short course antibiotic treatment

treatment failure in long course antibiotic treatment

RR = Relative Risk = Risk Ratio

Page 23: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

Combined RR = 1.94 (95% CI: 1.19–3.15)

Page 24: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

2. Effect sizes

Page 25: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

Example: testing the difference in the size of tumors in an experimental and a control group

What would you conclude if p = .11? p < .0001?

p-values or effect sizes?

Page 26: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

Misconceptions:◦ failure to reject the null hypothesis implies no

effect◦ a statistically significant p-value implies a

large effect

The interpretation of p-values

Page 27: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

Test of Significance = Size of Effect × Size of Study

Rosenthal, R. (1991). Meta-analytic procedures for social research. Newbury Park, CA: Sage

Page 28: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

Before being combined in a meta-analysis, findings from primary studies are summarized to a measure of effect size

There are several possible effect size indices: e.g. ◦ Two continuous variables: the correlation coefficient◦ One continuous, one dichotomous: the standardized

mean difference◦ Two dichotomous: the odds ratio, relative risk, …

To allow comparison over studies, a common measure is used, often a standardized one

In a meta-analysis, effect size measures are compared and combined

The use of effect sizes in meta-analysis

Page 29: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

Final exam

Predictive test 1 0

1 130(87 %)

20(13 %)

150(100 %)

0 30(60 %)

20(40%)

50(100 %)

160 40 200

Example: two dichotomous variables

1. Risk difference: .87-.60 = .272. Relative risk: .87/.60 = 1.453. Phi: (130 x 20 – 20 x 30)/sqrt (150 x 50 x 160 x 40) = 0.294. Odds ratio: (130 x 20 / 20 x 30) = 4.33

Page 30: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

◦ direct calculation based on means and standard deviations

◦ algebraically equivalent formulas (t-test)◦ exact probability value for a t-test◦ approximations based on continuous data (correlation

coefficient)

◦ Results of one way ANOVA with 3 or more groups◦ Results of ANCOVA◦ Results of multiple regression analysis

◦ approximations based on dichotomous data

Calculating & converting effect sizesExample: the standardized mean difference (g)(based on slides retrieved on March 6 2008, from http://mason.gmu.edu/~dwilsonb/ma.html)

Gre

atG

ood

Poo

r

Page 31: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

Methods of Calculating the Standardized Mean Difference

1 2 1 2

2 21 1 2 2

1 2

( 1) ( 1)

2

p

X X X Xg

s s n s n

n n

Direction Calculation Method

Page 32: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

Methods of Calculating the Standardized Mean Difference

1 2

p

X Xg

s

Calculation based on test statistics

1 2

1 2

1 1p

X Xt

sn n

1 2

1 2

n ng t

n n

exact p-values from a t-test or F-ratio can be convertedinto t-value and the above formula applied

Page 33: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

Methods of Calculating the Standardized Mean Difference

Calculation based on other effect size measures

2

2. .,

1

re g g

r

Other conversion formulae:

Lipsey, M. W., & Wilson, D. B. (2001). Practical meta-analysis. Thousand Oaks, CA: Sage.

Rosenthal, R. (1994). Parametric measures of effect size. In H. Cooper, & L. V. Hedges (Eds.), The handbook of research synthesis (pp. 231-244). New York: Russell Sage Foundation.

Page 34: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

3. Combining effect sizes of other designs

Page 35: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

35

Example: Stimulating response behavior in the classroom: A single-case study

Narayan, J. S., Heward, W. L., Gardner, R., Courson, F. H., Omness, C. K.

(1990), JABA, 23, 483-490.

Page 36: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

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Page 37: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

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Yi = 0 + 1 (Treatment)i+ ei met ei ~ N(0,2e)

Measuring and testing the effect

Page 38: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

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1

0

Page 39: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

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Effect size

1 B A 1 B ASC

e e

1 B ASC

p p

b x xd

s s

exp

exp

Cfr.: contrGC

contrGC

p

x xd

s

Page 40: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

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Page 41: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

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Results of the meta-analysis: Mean effect Treatment: 14.33 Standard error mean effect: 0.74

Page 42: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

o Expressing effects in (quasi-)experimental studies◦ Comparing experimental & control groups◦ Comparing one group under several conditions

o Expressing association in non-experimental studies◦ Comparing existing groups (e.g., male vs. female)◦ Expressing association between continuous variables

(e.g., relation between class size and performance)o Describing one single variable (e.g.,

prevalence rates, means, …)42

‘Effect’ sizes?

Page 43: Wim Van den Noortgate Katholieke Universiteit Leuven, Belgium Belgian Campbell Group Wim.VandenNoortgate@kuleuven-kortrijk.be Workshop systematic reviews

Check the internal validity of the design!(are there confounding variables?)

Pay attention with the interpretation of your results!

Association ≠ Causation !