GENERIC DATA

Learning outcomes:

You will have knowledge about and be able:

  • Conduct fixed and random effects meta-analysis
  • Measure effect size
  • Explore heterogeneity using sub-group and meta-regression analyses
  • Explore and address small study effects using funnel plot and trim and fill

STEPS in conducting Generic Data meta-analysis

  1. STEP 1 - LOAD DATA
  2. STEP 2 - DECLARE, UPDATE & DESCRIBE meta data
  3. STEP 3 - SUMMARIZE meta data by using a TABLE or a FOREST PLOT
  4. STEP 4- EXPLORE HETEROGENEITY - SUB-GROUP and META-REGRESSION analysis
  5. STEP 5- EXPLORE and ADDRESS SMALL-STUDY EFFECTS

Materials and setup

Laptop users: you will need a copy of Stata installed on your machine.

  • You can install a licensed version from https://warwick.ac.uk/services/its/servicessupport/software/list/stata
  • Find class materials at Click to Download
  • Download and extract to your desktop or any folder of your choice!

Link to YouTube Video Lecture

Click the image below:

STEP 1 - LOAD DATA

The meta command accepts effect sizes and confidence intervals, not just count data. By specifying two variables after commands, you indicate to Stata that the variables represent effect sizes and standard error.

Below are results from trials that examined effect of exercise on depression.

Contains data from Exercise for depression

  • Id: ID no. of study
  • study: First author of study
  • smd: Standardised mean difference
  • varsmd: Var(smd)
  • sesmd: SE(smd)
  • abstract: Published as abstract?
  • duration: Duration of follow-up (weeks)
  • itt: Intention-to-treat analysis?
  • alloc: Allocation concealment adequate?
  • Phd: Published as PhD thesis?

Option 1 Copy and paste from Excel (see attached exercise4deprsn.xlsx below)


edit

Option 2 Input raw directly into Stata (using ‘do file editor’ type doedit)

clear all input id str20 study smd varsmd sesmd abstract duration itt alloc phd 1 Mutrie -2.53 0.16 0.4 1 4 0 0 0 2 McNeil -1.07 0.1681 0.41 0 6 0 0 0 3 Reuter -2.1 0.16 0.4 1 10 0 0 0 4 Doyne -1.2 0.1849 0.43 0 8 0 0 0 5 Hess-Homeier -0.82 0.3249 0.57 0 8 0 0 1 6 Epstein -0.84 0.2116 0.46 0 8 0 0 1 7 Martinsen -1.16 0.0784 0.28 0 9 0 1 0 8 Singh -0.45 0.1156 0.34 0 10 1 1 0 9 Klein 0.25 0.2601 0.51 0 12 0 0 0 10 Veale -0.53 0.0576 0.24 0 12 0 1 0 end


Option 3 Load Stata data file directly from Excel file


import excel  using data/exercise4deprsn.xlsx, firstrow clear
describe
(10 vars, 10 obs)


Contains data
  obs:            10
 vars:            10
--------------------------------------------------------------------------------
              storage   display    value
variable name   type    format     label      variable label
--------------------------------------------------------------------------------
id              byte    %10.0g                id
study           str12   %12s                  study
smd             double  %10.0g                smd
varsmd          double  %10.0g                varsmd
sesmd           double  %10.0g                sesmd
abstract        byte    %10.0g                abstract
duration        byte    %10.0g                duration
itt             byte    %10.0g                itt
alloc           byte    %10.0g                alloc
phd             byte    %10.0g                phd
--------------------------------------------------------------------------------
Sorted by:
     Note: Dataset has changed since last saved.

Option 4 Load Stata data file directly (if already saved)


use data/exercise4deprsn.dta, clear

describe
(Excercise for depression)


Contains data from data/exercise4deprsn.dta
  obs:            10                          Excercise for depression
 vars:            10                          11 Oct 2015 21:16
                                              (_dta has notes)
--------------------------------------------------------------------------------
              storage   display    value
variable name   type    format     label      variable label
--------------------------------------------------------------------------------
id              byte    %3.0f               * ID no. of study
study           str12   %-12s                 First author of study
smd             float   %6.2f                 Standardised mean difference
varsmd          float   %7.4f                 Var(smd)
sesmd           float   %9.0g                 SE(smd)
abstract        byte    %-8.0g     noyes      Published as abstract?
duration        byte    %8.0g                 Duration of follow-up (weeks)
itt             byte    %-8.0g     noyes      Intention-to-treat analysis?
alloc           byte    %-8.0g     noyes      Allocation concealment adequate?
phd             byte    %-8.0g     noyes      Published as PhD thesis?
                                            * indicated variables have notes
--------------------------------------------------------------------------------
Sorted by: id

STEP 2- DECLARE, UPDATE & DESCRIBE meta data

meta set smd sesmd, studylabel(study) eslabel(Std. Mean Diff.)
Meta-analysis setting information

 Study information
    No. of studies:  10
       Study label:  study
        Study size:  N/A

       Effect size
              Type:  Generic
             Label:  Std. Mean Diff.
          Variable:  smd

         Precision
         Std. Err.:  sesmd
                CI:  [_meta_cil, _meta_ciu]
          CI level:  95%

  Model and method
             Model:  Random-effects
            Method:  REML

STEP 3- SUMMARIZE meta data by using a TABLE or a FOREST PLOT

Now, combine the results of trials, using the fixed- and random effects model


Q2.1 - What are the summary estimates and 95% CI for both fixed and random-effects

Click For Answer

- Fixed: -1.01 (95% CI -1.24 to -0.79); - Random -1.06 (95% CI -1.53 to -0.59)

Q2.2 - Are the results homogenous?

Click For Answer No, there is evidence of statistically significant substantial heterogeneity (I2 = 75%)

meta forestplot, nullrefline fixed
graph display
  Effect-size label:  Std. Mean Diff.
        Effect size:  smd
          Std. Err.:  sesmd
        Study label:  study

meta forestplot, nullrefline random
graph display
  Effect-size label:  Std. Mean Diff.
        Effect size:  smd
          Std. Err.:  sesmd
        Study label:  study

STEP 4- EXPLORE HETEROGENEITY - SUB-GROUP and META-REGRESSION analysis

Examine the pooled estimates differ according to following study characteristics:

  • Publication type
  • Intention to treat analysis
  • Allocation concealment
  • Published as PhD thesis or not
meta forestplot, nullrefline random subgroup(abstract)
graph display
  Effect-size label:  Std. Mean Diff.
        Effect size:  smd
          Std. Err.:  sesmd
        Study label:  study

meta forestplot, nullrefline random subgroup(itt)
graph display
  Effect-size label:  Std. Mean Diff.
        Effect size:  smd
          Std. Err.:  sesmd
        Study label:  study

meta forestplot, nullrefline random subgroup(alloc)
graph display
  Effect-size label:  Std. Mean Diff.
        Effect size:  smd
          Std. Err.:  sesmd
        Study label:  study

meta forestplot, nullrefline random subgroup(phd)
graph display
  Effect-size label:  Std. Mean Diff.
        Effect size:  smd
          Std. Err.:  sesmd
        Study label:  study

Univariable meta-regression

Fit a meta-regression model that explains the heterogeneity in terms of study-level covariates.


Q2.3 - Which study level covariates are significant?

Click For Answer

- Unadjusted (Abstract & duration) - Adjusted (Abstract)

Q2.4 - What percentage of heterogeneity is explained for these covariates?

Click For Answer

Abstract & duration jointly explained 100% of the between study variance


meta regress abstract
meta regress duration
estat bubbleplot
graph display
meta regress itt
meta regress alloc
meta regress phd
  Effect-size label:  Std. Mean Diff.
        Effect size:  smd
          Std. Err.:  sesmd

Random-effects meta-regression                      Number of obs  =        10
Method: REML                                        Residual heterogeneity:
                                                                tau2 =  .03269
                                                              I2 (%) =   19.02
                                                                  H2 =    1.23
                                                       R-squared (%) =   92.74
                                                    Wald chi2(1)   =     20.78
                                                    Prob > chi2    =    0.0000
------------------------------------------------------------------------------
    _meta_es |      Coef.   Std. Err.      z    P>|z|     [95% Conf. Interval]
-------------+----------------------------------------------------------------
    abstract |  -1.564109   .3431559    -4.56   0.000    -2.236682   -.8915357
       _cons |   -.750891   .1463283    -5.13   0.000    -1.037689   -.4640929
------------------------------------------------------------------------------
Test of residual homogeneity: Q_res = chi2(8) =  9.94    Prob > Q_res = 0.2690


  Effect-size label:  Std. Mean Diff.
        Effect size:  smd
          Std. Err.:  sesmd

Random-effects meta-regression                      Number of obs  =        10
Method: REML                                        Residual heterogeneity:
                                                                tau2 =   .2019
                                                              I2 (%) =   58.10
                                                                  H2 =    2.39
                                                       R-squared (%) =   55.16
                                                    Wald chi2(1)   =      7.02
                                                    Prob > chi2    =    0.0081
------------------------------------------------------------------------------
    _meta_es |      Coef.   Std. Err.      z    P>|z|     [95% Conf. Interval]
-------------+----------------------------------------------------------------
    duration |   .2097633    .079171     2.65   0.008     .0545909    .3649357
       _cons |  -2.907511   .7239578    -4.02   0.000    -4.326442    -1.48858
------------------------------------------------------------------------------
Test of residual homogeneity: Q_res = chi2(8) = 18.11    Prob > Q_res = 0.0204

  Effect-size label:  Std. Mean Diff.
        Effect size:  smd
          Std. Err.:  sesmd

Random-effects meta-regression                      Number of obs  =        10
Method: REML                                        Residual heterogeneity:
                                                                tau2 =   .4719
                                                              I2 (%) =   76.66
                                                                  H2 =    4.28
                                                       R-squared (%) =    0.00
                                                    Wald chi2(1)   =      0.70
                                                    Prob > chi2    =    0.4028
------------------------------------------------------------------------------
    _meta_es |      Coef.   Std. Err.      z    P>|z|     [95% Conf. Interval]
-------------+----------------------------------------------------------------
         itt |   .6790167   .8116419     0.84   0.403    -.9117722    2.269806
       _cons |  -1.129017   .2668869    -4.23   0.000    -1.652105    -.605928
------------------------------------------------------------------------------
Test of residual homogeneity: Q_res = chi2(8) = 32.33    Prob > Q_res = 0.0001


  Effect-size label:  Std. Mean Diff.
        Effect size:  smd
          Std. Err.:  sesmd

Random-effects meta-regression                      Number of obs  =        10
Method: REML                                        Residual heterogeneity:
                                                                tau2 =   .4383
                                                              I2 (%) =   75.10
                                                                  H2 =    4.02
                                                       R-squared (%) =    2.64
                                                    Wald chi2(1)   =      1.01
                                                    Prob > chi2    =    0.3142
------------------------------------------------------------------------------
    _meta_es |      Coef.   Std. Err.      z    P>|z|     [95% Conf. Interval]
-------------+----------------------------------------------------------------
       alloc |   .5186852   .5153992     1.01   0.314    -.4914787    1.528849
       _cons |  -1.235379   .3032112    -4.07   0.000    -1.829662   -.6410955
------------------------------------------------------------------------------
Test of residual homogeneity: Q_res = chi2(8) = 28.46    Prob > Q_res = 0.0004


  Effect-size label:  Std. Mean Diff.
        Effect size:  smd
          Std. Err.:  sesmd

Random-effects meta-regression                      Number of obs  =        10
Method: REML                                        Residual heterogeneity:
                                                                tau2 =   .5089
                                                              I2 (%) =   79.16
                                                                  H2 =    4.80
                                                       R-squared (%) =    0.00
                                                    Wald chi2(1)   =      0.16
                                                    Prob > chi2    =    0.6910
------------------------------------------------------------------------------
    _meta_es |      Coef.   Std. Err.      z    P>|z|     [95% Conf. Interval]
-------------+----------------------------------------------------------------
         phd |   .2718996   .6840508     0.40   0.691    -1.068815    1.612615
       _cons |  -1.102629   .2853771    -3.86   0.000    -1.661957   -.5432998
------------------------------------------------------------------------------
Test of residual homogeneity: Q_res = chi2(8) = 35.15    Prob > Q_res = 0.0000
foreach factor of varlist abstract duration itt alloc phd {
	meta regress  `factor'
}
  Effect-size label:  Std. Mean Diff.
        Effect size:  smd
          Std. Err.:  sesmd

Random-effects meta-regression                      Number of obs  =        10
Method: REML                                        Residual heterogeneity:
                                                                tau2 =  .03269
                                                              I2 (%) =   19.02
                                                                  H2 =    1.23
                                                       R-squared (%) =   92.74
                                                    Wald chi2(1)   =     20.78
                                                    Prob > chi2    =    0.0000
------------------------------------------------------------------------------
    _meta_es |      Coef.   Std. Err.      z    P>|z|     [95% Conf. Interval]
-------------+----------------------------------------------------------------
    abstract |  -1.564109   .3431559    -4.56   0.000    -2.236682   -.8915357
       _cons |   -.750891   .1463283    -5.13   0.000    -1.037689   -.4640929
------------------------------------------------------------------------------
Test of residual homogeneity: Q_res = chi2(8) =  9.94    Prob > Q_res = 0.2690

  Effect-size label:  Std. Mean Diff.
        Effect size:  smd
          Std. Err.:  sesmd

Random-effects meta-regression                      Number of obs  =        10
Method: REML                                        Residual heterogeneity:
                                                                tau2 =   .2019
                                                              I2 (%) =   58.10
                                                                  H2 =    2.39
                                                       R-squared (%) =   55.16
                                                    Wald chi2(1)   =      7.02
                                                    Prob > chi2    =    0.0081
------------------------------------------------------------------------------
    _meta_es |      Coef.   Std. Err.      z    P>|z|     [95% Conf. Interval]
-------------+----------------------------------------------------------------
    duration |   .2097633    .079171     2.65   0.008     .0545909    .3649357
       _cons |  -2.907511   .7239578    -4.02   0.000    -4.326442    -1.48858
------------------------------------------------------------------------------
Test of residual homogeneity: Q_res = chi2(8) = 18.11    Prob > Q_res = 0.0204

  Effect-size label:  Std. Mean Diff.
        Effect size:  smd
          Std. Err.:  sesmd

Random-effects meta-regression                      Number of obs  =        10
Method: REML                                        Residual heterogeneity:
                                                                tau2 =   .4719
                                                              I2 (%) =   76.66
                                                                  H2 =    4.28
                                                       R-squared (%) =    0.00
                                                    Wald chi2(1)   =      0.70
                                                    Prob > chi2    =    0.4028
------------------------------------------------------------------------------
    _meta_es |      Coef.   Std. Err.      z    P>|z|     [95% Conf. Interval]
-------------+----------------------------------------------------------------
         itt |   .6790167   .8116419     0.84   0.403    -.9117722    2.269806
       _cons |  -1.129017   .2668869    -4.23   0.000    -1.652105    -.605928
------------------------------------------------------------------------------
Test of residual homogeneity: Q_res = chi2(8) = 32.33    Prob > Q_res = 0.0001

  Effect-size label:  Std. Mean Diff.
        Effect size:  smd
          Std. Err.:  sesmd

Random-effects meta-regression                      Number of obs  =        10
Method: REML                                        Residual heterogeneity:
                                                                tau2 =   .4383
                                                              I2 (%) =   75.10
                                                                  H2 =    4.02
                                                       R-squared (%) =    2.64
                                                    Wald chi2(1)   =      1.01
                                                    Prob > chi2    =    0.3142
------------------------------------------------------------------------------
    _meta_es |      Coef.   Std. Err.      z    P>|z|     [95% Conf. Interval]
-------------+----------------------------------------------------------------
       alloc |   .5186852   .5153992     1.01   0.314    -.4914787    1.528849
       _cons |  -1.235379   .3032112    -4.07   0.000    -1.829662   -.6410955
------------------------------------------------------------------------------
Test of residual homogeneity: Q_res = chi2(8) = 28.46    Prob > Q_res = 0.0004

  Effect-size label:  Std. Mean Diff.
        Effect size:  smd
          Std. Err.:  sesmd

Random-effects meta-regression                      Number of obs  =        10
Method: REML                                        Residual heterogeneity:
                                                                tau2 =   .5089
                                                              I2 (%) =   79.16
                                                                  H2 =    4.80
                                                       R-squared (%) =    0.00
                                                    Wald chi2(1)   =      0.16
                                                    Prob > chi2    =    0.6910
------------------------------------------------------------------------------
    _meta_es |      Coef.   Std. Err.      z    P>|z|     [95% Conf. Interval]
-------------+----------------------------------------------------------------
         phd |   .2718996   .6840508     0.40   0.691    -1.068815    1.612615
       _cons |  -1.102629   .2853771    -3.86   0.000    -1.661957   -.5432998
------------------------------------------------------------------------------
Test of residual homogeneity: Q_res = chi2(8) = 35.15    Prob > Q_res = 0.0000

Multivariale meta-regression

meta regress abstract duration
  Effect-size label:  Std. Mean Diff.
        Effect size:  smd
          Std. Err.:  sesmd

Random-effects meta-regression                      Number of obs  =        10
Method: REML                                        Residual heterogeneity:
                                                                tau2 = 5.3e-08
                                                              I2 (%) =    0.00
                                                                  H2 =    1.00
                                                       R-squared (%) =  100.00
                                                    Wald chi2(2)   =     30.61
                                                    Prob > chi2    =    0.0000
------------------------------------------------------------------------------
    _meta_es |      Coef.   Std. Err.      z    P>|z|     [95% Conf. Interval]
-------------+----------------------------------------------------------------
    abstract |  -1.243886   .3412327    -3.65   0.000     -1.91269    -.575082
    duration |   .1207103   .0533561     2.26   0.024     .0161343    .2252863
       _cons |  -1.916086   .5312603    -3.61   0.000    -2.957337   -.8748354
------------------------------------------------------------------------------
Test of residual homogeneity: Q_res = chi2(7) =  4.82    Prob > Q_res = 0.6813

STEP 5- EXPLORE and ADDRESS SMALL-STUDY EFFECTS


Q2.5 - Examine whether there is evidence of publication bias?

Click For Answer

No evidence of publication bias


meta funnelplot, metric(invse)
graph display
  Effect-size label:  Std. Mean Diff.
        Effect size:  smd
          Std. Err.:  sesmd
              Model:  Common-effect
             Method:  Inverse-variance

meta bias, egger
  Effect-size label:  Std. Mean Diff.
        Effect size:  smd
          Std. Err.:  sesmd

Regression-based Egger test for small-study effects
Random-effects model
Method: REML

H0: beta1 = 0; no small-study effects
            beta1 =      0.48
      SE of beta1 =     2.804
                z =      0.17
       Prob > |z| =    0.8641
meta trimfill
  Effect-size label:  Std. Mean Diff.
        Effect size:  smd
          Std. Err.:  sesmd

Nonparametric trim-and-fill analysis of publication bias
Linear estimator, imputing on the right

Iteration                            Number of studies =     10
  Model: Random-effects                       observed =     10
 Method: REML                                  imputed =      0

Pooling
  Model: Random-effects
 Method: REML

---------------------------------------------------------------
             Studies |  Std. Mean Diff.    [95% Conf. Interval]
---------------------+-----------------------------------------
            Observed |           -1.056      -1.541      -0.570
  Observed + Imputed |           -1.056      -1.541      -0.570
---------------------------------------------------------------

GENERIC DATA

STEPS in conducting Generic Data meta-analysis

  1. STEP 1 - LOAD DATA
  2. STEP 2 - DECLARE, UPDATE & DESCRIBE meta data
  3. STEP 3 - SUMMARIZE meta data by using a TABLE or a FOREST PLOT
  4. STEP 4- EXPLORE HETEROGENEITY - SUB-GROUP and META-REGRESSION analysis
  5. STEP 5- EXPLORE and ADDRESS SMALL-STUDY EFFECTS

Sections

  1. Overview meta-analysis data types
  2. Introduction to Stata
  3. Meta-analysis of binary data
  4. Meta-analysis of generic data
  5. Meta-analysis of continuous data
  6. Meta-analysis of prevalence data