csp-770-meta-analysis

Steven Vannoy
10/22/16

Three Primary Goals of the Analysis

  1. Calculate a summary (global, aggregated) effect size across multiple studies of the same phenomenon
  2. Estimate the precision (heterogeneity) of the aggregated effect
    2.1 - If the various ES vary a lot, it is a sign they may be not be comparable.
  3. If there is a high level heterogeneity
    3.1 Attempt to characterize source of heterogeniety
    3.2 Covariates may explain the heterogeneity

Effect Sizes

Choice of ES depends on research question

ES Outcome type Predictor type
Correlation coefficient Continuous Continuous
Standardized difference (d or g) Continuous Dichotomous
Odds ratio (or Log odds) Dichotomous Dichotomous

Preparing Your (RCT) Data

  • For each study you will need
    1. Sample size of each group (study)
    2. The average change of each group
    3. The standard deviation of change scores for each group
  • Depending on the package, you calculate standardized effect sizes and then analyze or provide just the raw data

  • When you have multiple related effects in a study you can aggregate taking their correlation into account

    • See Borenstein, Hedges, Higgins, & Rothstein (BHHR; 2009)
    • The MAd package provides the function agg to do this

Estimating the Summary Effect

  • The summary effect is a weighted average of all effects
    • The weights are the inverse of the ES variance across studies
      • Variance is a largely a function of sample size
      • Thus larger studies make larger contributions to the effect
  • The summary effect can be calculated as a:
    • fixed effect: Results do not generalize beyond the sample of studies
    • random effect: Results do generalize to all such studies

Heterogeneity

Some heterogeneity is to be expected, how much is too much?

  • Q is the chi-squared statistic evaluating chance variation
  • p < .0x indicates that variance of ESs is not random
  • \( I^2 \) is a measure of the variance associated with heterogeneity
    • 0% to 40%: may not be important
    • 30% to 60%: may represent problematic heterogeneity
    • 50% to 90%: may represent significant problems
    • 75% to 100%: considerable heterogeneity

Example 1 - The Cochrane Logo

Study Evts-Tx n-Tx Evts-Ctrl n-Ctrl
Auckland 36 532 60 538
Block 1 69 5 61
Doran 4 81 11 63
Gamsu 14 131 20 137
Morrison 3 67 7 59
Papageorgiou 1 71 7 75
Tauesch 8 56 10 71

Example 1 - The Cochrane Logo

Fit a fixed effects model

Fixed effects ( Mantel-Haenszel ) meta-analysis
Call: meta.MH(ntrt = n.trt, nctrl = n.ctrl, ptrt = ev.trt, pctrl = ev.ctrl, 
    names = name, data = cochrane)
------------------------------------
               OR (lower  95% upper)
Auckland     0.58    0.38       0.89
Block        0.16    0.02       1.45
Doran        0.25    0.07       0.81
Gamsu        0.70    0.34       1.45
Morrison     0.35    0.09       1.41
Papageorgiou 0.14    0.02       1.16
Tauesch      1.02    0.37       2.77
------------------------------------
Mantel-Haenszel OR =0.53 95% CI ( 0.39,0.73 )
Test for heterogeneity: X^2( 6 ) = 6.9 ( p-value 0.3303 )

A Forest Plot of the Cochrane Data Set plot of chunk unnamed-chunk-5

Example 1 - The Cochrane Logo

Fit a random effects model

Random effects ( DerSimonian-Laird ) meta-analysis
Call: meta.DSL(ntrt = n.trt, nctrl = n.ctrl, ptrt = ev.trt, pctrl = ev.ctrl, 
    names = name, data = cochrane)
------------------------------------
               OR (lower  95% upper)
Auckland     0.58    0.38       0.89
Block        0.16    0.02       1.45
Doran        0.25    0.07       0.81
Gamsu        0.70    0.34       1.45
Morrison     0.35    0.09       1.41
Papageorgiou 0.14    0.02       1.16
Tauesch      1.02    0.37       2.77
------------------------------------
SummaryOR= 0.53  95% CI ( 0.37,0.78 )
Test for heterogeneity: X^2( 6 ) = 6.86 ( p-value 0.334 )
Estimated random effects variance: 0.03 

Example 1 - The Cochrane Logo

What is the difference between the fixed and random effects model?

plot of chunk unnamed-chunk-7

Example 2 - Continuous Outcomes

Mean Change in two-condition RCT

Study n-tx Avg Tx Change n-cntrl Avg Cntrl Change
154 46 0.232 48 -0.003
156 30 0.281 26 0.027
157 75 0.189 72 0.044
162 12 0.093 12 0.228
163 32 0.162 34 0.006
166 31 0.184 31 0.094
303 27 0.661 27 -0.006
306 46 0.137 47 -0.006

Example 2 - Continuous Outcomes

Mean Change in two-condition RCTs

Study Effect Sizes and Weights
study_id SMD lci uci weight
154 0.700 0.283 1.117 18.90
156 0.694 0.152 1.236 11.90
157 0.245 -0.079 0.570 28.54
162 -0.425 -1.235 0.386 5.59
163 0.499 0.009 0.990 14.23
166 0.229 -0.270 0.729 13.78
303 0.714 0.162 1.265 11.52
306 0.400 -0.011 0.811 19.41

Example 2 - Continuous Outcomes

Results of Meta-Analysis

Meta-Analysis Parameters
model SMD lci uci z p
Fixed 0.420 0.257 0.584 5.05 0.0000
Random 0.423 0.247 0.599 4.71 0.0000
Quantifying heterogeneity:
Tau^2 H^2 lci uci I^2 lci uci
0.008 1.18 1 1.76 0.282 0 0.678
Test of heterogeneity:
Q d.f p-value
9.75 7 0.203

Example 2 - Continuous Outcomes

Funnel Plot angina forest plot

Example 2 - Continuous Outcomes

Forrest Plot
plot of chunk unnamed-chunk-11

Example 2 - Continuous Outcomes

Test of Funnel Plot Assymetry

Linear regression test of funnel plot asymmetry

t = -0.337, df = 6, p = 0.747


Bias Estimate
bias se slope
bias -0.64 1.9 0.57

Example 3 - Adjusting for Heterogeneity

The Study Data

id nT m1T sd1T nC m1C sd1C dose
204 21 21 5.8 21 18 6.5 10
493 19 21 6.0 19 18 5.2 11
506 27 21 7.3 27 17 6.9 9
509 35 22 6.3 35 15 6.8 11
359 20 20 4.9 20 16 6.5 8
661 27 19 4.6 27 15 5.2 10
549 35 23 5.7 35 16 4.0 14
119 31 18 5.8 31 19 4.5 7

Example 3 - Adjusting for Heterogeneity

Results of Meta-Analysis (without covariates)

Meta-Analysis Parameters (Fixed & Random Models)
model SMD lci uci z p
Fixed 0.68 0.48 0.88 6.7 0.0000
Random 0.68 0.31 1.04 3.7 0.0002
Quantifying heterogeneity:
Tau^2 H^2 lci uci I^2 lci uci
0.19 1.9 1.3 2.7 0.72 0.41 0.86
Test of heterogeneity:
Q d.f p-value
25 7 0.001

Example 3 - Adjusting for Heterogeneity

Funnel plot with heterogeneity
plot of chunk unnamed-chunk-16

Example 3 - Adjusting for Heterogeneity

Results of Meta-Analysis (WITH covariates)

Meta-Analysis Parameters (Fixed & Random Models)
predictor SMD lci uci z p
Intercept -1.44 -2.40 -0.47 -2.9 0.0034
Dose 0.21 0.12 0.31 4.4 0.0000
Intercept -1.44 -2.40 -0.47 -2.9 0.0034
Dose 0.21 0.12 0.31 4.4 0.0000

Example 3 - Adjusting for Heterogeneity

Control for different doses

[1] "Tau^2 = 0.000"
[1] "I^2:  = 0.000"
[1] "H^2:  = 1.000"
[1] "Test for Residual Heterogeneity"
[1] "Q = 5.22, d.f = 6, p-val = 0.5160"
[1] "Test for Moderators Heterogeneity"
[1] "Q = 19.39, d.f = 1, p-val = 0.0000"

Example 3 - Adjusting for Heterogeneity

Control for different doses
plot of chunk unnamed-chunk-19