Mediator analysis within field trials

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							Mediation Models

Laura Stapleton
UMBC
Mediation Models

Tasha Beretvas
University of Texas at Austin
Session outline

   What is mediation?
   Basic single mediator model
   Short comment on causality
   Tests of the hypothesized mediation effect
   Mediation models for cluster randomized trials
   Brief mention of advanced issues
What is mediation?
   A mediator explains how or why two
    variables are related.
     Inthe context of interventions, a mediator
      explains how or why a Tx effect occurs
 A mediator is thought of as the
  mechanism or processes through which
  a Tx influences an outcome (Barron & Kenny, 1986).
 If X  M and M  Y, then M is a mediator
          X causes proximal variable, M, to vary which itself
           causes distal, variable,Y, to vary
What is mediation?
   Mediational process can be
     Observed   or latent
     Internal or external
     At the individual or cluster level
     Based on multiple or sequential processes

   Who cares?!
     Mediation   analyses can identify important
      processes/mechanisms underlying effective
      (or ineffective!) treatments thereby providing
      important focal points for future interventions.
Mediation Examples
 Bacterial exposure  Disease
 Bacterial exposure  Infection  Disease
 Stimulus  Response
     Might
          work for simple organisms (amoebae!),
     however, for more complex creatures:
 Stimulus  Organism  Response
 Stimulus  Expectancy  Response
     Monkey  and lettuce example
     Maze-bright, maze-dull rats and maze
      performance example
Mediation Examples


 Intervention  Outcome
 Intervention  Receptivity  Outcome
 Intervention  Tx Fidelity  Outcome
 Intervention  Tch Confid Outcome
 Intervention  Soc Comp Achievement
 Intervention  Phon Aware  Reading
 Intervention  Peer Affil  Delinq Beh
Mediation  Moderation

   A moderator explains when an effect
    occurs
     Relationship  between X and Y changes for
      different values of M
     More in later session of workshop…
Basic (single-level) mediation model

 Treatment          c             Outcome
                                                 Yi   0  1 Ti  ei


                  Mediator                        M i   0  1 Ti  ei
             a                b
 Treatment                        Outcome

                    c’                           Yi   0'  1' M i   2' Ti  ei'


        total effect = indirect effect + direct effect
                  c=         ab   +         c’
Causality concerns
   Just because you estimate the model
                  XMY
    does not mean that the relationships are
    causal
     Unless  you manipulate M, causal inferences
      are limited.
   Mediation model differs from Mediation
    design
Causality concerns – mediation model
   Remember, if the mediator is not typically
    manipulated, causal interpretations are limited
                      Mediator
                                                   Z
                a         M          b
    Treatment
                    Ok!                 Outcome

       T                                   Y
   Possible misspecification
   For now, be sure to substantively justify the causal
    direction and “assume or hypothesize that M causes Y
    and assuming that, here’s the strength of that effect…”
   In future research, manipulate mediator
Tests of the hypothesized mediation
effect
                          Mediator

                      a    M         b
          Treatment                      Outcome

             T              c’             Y
   The estimate of the indirect effect, ab, is based
    on the sample
   To infer that a non-zero αβ exists in the
    population, a test of the statistical significance of
    ab is needed
   Several approaches have been suggested and
    differ in their ability to “see” a true effect (power)
Tests of the hypothesized mediation
effect
   Causal steps approach (Baron & Kenny)
   Test of joint significance
   z test of ab (with normal theory confidence interval)
   Asymmetric confidence interval (Empirical M or
    distribution of the product)
   Bootstrap resampling
Causal steps approach
   Step 1: test the effect of T on Y (path c)
    Treatment          c          Outcome




 Step 2: test the effect of T on M (path a)
                       Mediator

                   a
       Treatment
Causal steps approach
 Step 3: test the effect of M on Y, controlling for T
(path b)
                Mediator

                           b
    Treatment                  Outcome

                  c’



Step 4: to decide on partial or complete
mediation, test the effect of T on Y, controlling for
M (path c’)
Causal steps approach: performance
   Step 1 may be non-significant when true
    mediation exists
                                      Mediator

                               +2     FdF             +3
       What if…    Treatment                                Outcome

                      T                  -6                Dep


                                     Mediator

                               +2    FdF              +3
       or…        Treatment                                Outcome

                     T          +3               -2        Dep
                                     Mediator

                                     SS
Causal steps approach: performance

   Lacks power
     Power  is a function of the product of the
      power to test each of the three paths
     Power discrepancy worsens for smaller n and
      smaller effects
   Lower Type I error rate than expected
     i.e.,   too conservative
Test of joint significance
    Very similar to causal steps approach
                       Mediator

                   a              b
       Treatment                      Outcome

                         c’


 1st: test the effect of T on M (path a)

 2nd: test the effect of M on Y, controlling for T (path
b)
 If both significant, then infer significant mediation
Test of joint significance: performance
   Better power than causal steps approach
   Type I error rate slightly lower than expected
   Power nearly as good as newer methods in single-
    level models
   Power lower than other methods in multilevel
    models
   No confidence interval around the indirect effect is
    available
z test of ab product
                         ab
   Calculate z =
                        seab

 Sobel’s     seab =       a 2 seb  b 2 sea
                                 2         2




 Compare z test value to critical values from the
standard normal distribution

   Can also calculate confidence interval around ab
       CI =     ab  ( zcritical )( seab )
z test of ab product: performance
   One of the least powerful approaches
   Type I error rate much lower than expected .05.
   Single-level models, it approaches the power of
    other methods when sample size are 500 or
    greater, or effect sizes are large
   Multilevel models, it never reaches the levels of
    other models although it does get closer
    although still lower
   Problem is that the ab product is not normally
    distributed, so critical values are inappropriate
   How is the ab product distributed?
Sampled 1,000 a ~ N(0,1) and of b ~ N(0,1)

 200                                                         200

            Distribution of path a                                           Distribution of path b
 150                                                         150



 100                                                         100



 50                                                          50



  0                                                           0
       -4   -3   -2   -1   0         1    2    3    4              -4       -3       -2       -1     0   1   2   3   4




                               200



                               150

                                                                                                   Distribution of
                               100
                                                                                                   product of axb
                               50



                                0
                                     -4   -3   -2   -1   0     1        2        3        4
Empirical M-test (asymmetric CI)
   Determines empirical (more leptokurtic) distribution
    of z of the ab product (not assuming normality)
     αβ=0: dist’n is leptokurtic and symmetric
     αβ>0: dist’n is less leptokurtic and +ly skewed
     αβ<0: dist’n is less leptokurtic and -ly skewed

   Due to asymmetry, different upper and lower critical
    values needed to calculate asymmetric confidence
    intervals (CIs).
   Meeker derived tables for various combinations of
    Za and Zb values (increments of 0.4) that could be
    used to calculate asymmetric CIs.
Empirical M-test (asymmetric CI)
   MacKinnon et al created PRODCLIN that,
    given a, b, and their SEs, determines the
    distribution of ab and relevant critical
    values for calculating asymmetric CI.
                             (MacKinnon & Fritz, 2007, 384-389).

   Confidence interval limits:
             ab  (CVlower )( seab )
             ab  (CVupper )( seab )
   If CI does not include zero, then significant
Empirical M-test: performance

   Good balance of power while maintaining
    nominal Type I error rate
   Performed well in both single-level and
    multi-level tests of mediation
   Only bootstrap resampling methods had
    (very slightly) better power than this
    method
   PRODCLIN software is easy to use
Bootstrap resampling methods
   Determines empirical distribution of the ab
    product
   Several variations
      Parametric percentile
      Non-parametric percentile
      Bias-corrected versions of both
   Can bootstrap cases or bootstrap residuals.
     Itis typical in multilevel designs to bootstrap
      residuals.
Parametric percentile bootstrap
   With original sample, run the analysis and obtain
    estimates of variance(s) of residuals
   New residuals are then resampled from a
    distribution ~N(0,σ2) (thus, the “parametric”).
   New values of M are created by using the fixed
    effects estimates from the original analysis, T
    and the resampled residual(s).
   New values of Y are created using the fixed
    effects, and T and M values and residual(s).
   Then, the analysis is run and the ab product is
    estimated
Parametric percentile bootstrap
   The process of resampling and estimating ab is
    repeated many times (commonly 1,000 times)
   The ab estimates are then ordered
   With 1,000 estimates, the 25th and the 975th are
    taken as the lower and upper limits of the 95%
    (empirically derived) CI.
   Note that the CI limits may not be symmetric
    around the original ab estimate
   If CI does not include zero, then significant
    mediation
Non-parametric percentile bootstrap
   The parametric bootstrap involves the
    assumption that the residuals are normally
    distributed
   Instead, residuals can be resampled with
    replacement from the empirical distribution of
    actual residuals (saved from the original
    sample’s analysis)
   The remaining process is the same as for the
    parametric version
Bias-corrected bootstrap

   With both the parametric and non-parametric
    bootstrap, the initial ab product may not be at
    the median of the bootstrap ab distribution
   Thus, the initial ab estimate is biased
   BC-bootstrap procedures “shift” the confidence
    interval to adjust for the difference in the initial
    estimate and the median
Bootstrap resampling methods:
performance
   Resampling methods provide the most power
    and accurate Type I error rates of all methods
   Parametric has best confidence interval
    coverage
   BC-parametric had best power, especially with
    low effect sizes with normal and non-normally
    distributed residuals; Type I error rate was
    slightly high for multilevel analyses
   Non-parametric had the most accurate Type I
    error rates; good overall power
   BC Non-parametric had good power
   But … complicated to program
Summary: tests of the hypothesized
mediation effect
 Causal steps approach        
 Test of joint significance    OK for single level…
 z test of ab                 
 Empirical M                   Yes! Easy!
 Bootstrap resampling          Yes! Not quite as easy…
                               but does have the most power
Example for today
 Social-emotional curriculum = Tx
 Child social competence = outcome
 Randomly selected classrooms (one per
  school)
 Why would Tx affect outcome?
     Teacher attitude about importance?
     Child understanding of others’ behaviors?
     Puppet show down-time soothes child?

   Researcher should think in advance of
    possible mediators to measure
Mediation models for cluster
randomized trials
   Extend basic model to situations when treatment
    is administered at cluster level
   Model depends on whether mediator is
    measured at cluster or individual level
   Definition (Krull & MacKinnon, 2001) depends on level at
    which each variable is measured: T → M →Y
     Upper-level mediation [2→2→1]
     Cross-level mediation [2→1→1]
     Cross-level and upper-level mediation
      [2→(1 & 2) →1]
Measured variable partitioning

   First, consider that any variable may    Cluster
    be partitioned into individual level       uoj
    components and cluster level
    components

     Yij   00  u 0 j  rij                  Yij



    Note: No intercepts depicted            Individual
                                               rij
Mediation model possibilities

     Tx            M                Y
   Cluster       Cluster         Cluster




     Tx            M               Y



     Tx             M               Y
  Individual    Individual      Individual
Data Example Context

   Cluster randomized trial (hierarchical design)
   14 preschools: ½ treatment, ½ control
    6   kids per school (/classroom)
   Socio-emotional curriculum
   Outcome is child social competence behavior
   Possible mediators: teacher attitude about
    importance of including this kind of training in
    classroom, child socio-emotional knowledge
   Sample data are on handout
Total effect of treatment
  Before we examine mediation, let’s examine
  the total effect of treatment on the outcome…
                                                     
                                                    u0 j

               Tx                   01      Y
             Cluster                      Cluster



                Tx                          Y


           
   Yij   0 j  eij                         Y
                                          Cluster
                           
    0 j   00   01 T j  u0 j
                                                     rij
Total effect of treatment: FE Results




 Final estimation of fixed effects:
 ----------------------------------------------------------------------------
                                       Standard             Approx.
     Fixed Effect        Coefficient   Error      T-ratio   d.f.     P-value
 ----------------------------------------------------------------------------
 For        INTRCPT1, B0
     INTRCPT2, G00         34.357143   1.029102    33.386        12    0.000
            T, G01          4.238095   1.455370     2.912        12    0.014
 ----------------------------------------------------------------------------



                       c
Upper-level mediation model (2→2→1)
                   01           M           ’01              
                                                              u0 j
                               Cluster
        Tx                                             Y
      Cluster                              ’02     Cluster



         Tx                        M                  Y


     M j   00   01T j  u0 j                       Y
                                                    Cluster

    Yij   '0 j  r 'ij                                      rij
                                       
      0 j   00   01 M j   02 T j  u0 j
Upper-level mediation model: Results
  To estimate the a path, I ran an OLS
  regression in SPSS using the Level 2 file
                       M j   00   01T j  u0 j
                                                 a
                                     Coe fficients

                         Unstandardiz ed         Standardized
                           Coef f icients        Coef f icients
 Model                    B         Std. Error       Beta          t       Sig.
 1       (Cons tant)      9.429           .444                    21.228     .000
         T                 .714           .628            .312     1.137     .278
   a. Dependent Variable: M1




   What is the estimate of a and its SE?
Upper-level mediation model: Results
  To estimate the b path, I ran a model in HLM




 Final estimation of fixed effects:
 ----------------------------------------------------------------------------
                                       Standard             Approx.
     Fixed Effect        Coefficient   Error      T-ratio   d.f.     P-value
 ----------------------------------------------------------------------------
 For        INTRCPT1, B0
     INTRCPT2, G00         34.640907   1.036530    33.420        11    0.000
            M1, G01         0.794540   0.656229     1.211        11    0.252
            T, G02          3.670567   1.502879     2.442        11    0.033
 ----------------------------------------------------------------------------


  What is the estimate of b and its SE?
  What is the estimate of c’ and its SE?
Upper-level mediation model: Results
                        M                    
                                            u0 j
                      Cluster
         Tx                          Y
       Cluster    3.671           Cluster



         Tx               M         Y


                                     Y
                                  Cluster
   Direct effect = 3.671                 rij
   Indirect effect = (.714)(.795) = .568
   Total effect = DE + IE = 3.671 + .568 = 4.239
Upper-level mediation model: Results
   Causal steps approach        No   Step 1 significant, but
                                 .    not Steps 2 and 3


   Test of joint significance   No   Neither path a nor path
                                 .    b are significant


   z test of ab product         No   se=.68, z=.83, p=.41
                                 .    95% CI = -.78 to 1.91


   Empirical-M test             No   95% CI = -.47 to 2.26
                                 .

   BC parametric bootstrap      No   95% CI = -.42 to 3.68
                                 .
Upper-level mediation model: Results
   PRODCLIN http://www.public.asu.edu/~davidpm/ripl/ Prodclin/
Cross-level mediation model (2→1→1)
Model A                                                      Model B

                                                      u0 j
                                                                                                                                    '
                                                                                                                                   u0 j
                       γ01         Mediator

          Treatment
                                  CLUSTER
                                                              Treatment
                                                                                 γ’01                          Outcome
          CLUSTER                                             CLUSTER                                          CLUSTER




                                  Mediator                                                 Mediator
          Treatment                                          Treatment                                         Outcome



                                  Mediator                                                 Mediator     γ’10
                                  INDIVIDUAL                                               INDIVIDUAL
                                                                                                               Outcome
                                                                                                               INDIVIDUAL



                                               rij'
                                                                   Yij   '0 j   '1 j Mij  r 'ij                        rij'
      M ij   0 j  rij ,
                                                                           '0 j   '00   '01Tj  u'0 j
       0 j   00   01T j  u0 j
                                                                           '1 j   '10
Cross-level mediation model: Results
  To estimate the a path:




 Final estimation of fixed effects:
 ----------------------------------------------------------------------------
                                       Standard             Approx.
     Fixed Effect        Coefficient   Error      T-ratio   d.f.     P-value
 ----------------------------------------------------------------------------
 For        INTRCPT1, B0
     INTRCPT2, G00         39.309524   0.845210    46.509        12    0.000
            T, G01          2.642857   1.195308     2.211        12    0.047
 ----------------------------------------------------------------------------


  What is a and its SE?
Cross-level mediation model: Results
  To estimate the b path:




  Final estimation of fixed effects:
 ----------------------------------------------------------------------------
                                       Standard             Approx.
     Fixed Effect        Coefficient   Error      T-ratio   d.f.     P-value
 ----------------------------------------------------------------------------
 For        INTRCPT1, B0
     INTRCPT2, G00         35.138955   0.941637    37.317        12    0.000
            T, G01          2.674528   1.358185     1.969        12    0.072
 For M2_GRAND slope, B1
     INTRCPT2, G10          0.591620   0.142895     4.140        81    0.000
 ----------------------------------------------------------------------------

  What is b and its SE?                       And for c’?
Cross-level mediation model: Results
Model A                                          Model B

                                          u0 j
                                                                                                        '
                                                                                                       u0 j
                       Mediator

          Treatment
                      CLUSTER
                                                  Treatment
                                                              2.675                Outcome
          CLUSTER                                 CLUSTER                          CLUSTER




                      Mediator                                        Mediator
          Treatment                              Treatment                         Outcome



                      Mediator                                        Mediator
                      INDIVIDUAL                                      INDIVIDUAL
                                                                                   Outcome
                                                                                   INDIVIDUAL



                                   rij'
                                                                                                rij'
     Direct effect = 2.675
     Indirect effect = (2.643)(.592) = 1.564
     Total effect = 2.675 + 1.564 = 4.239
Cross-level mediation model: Results

   Causal steps approach        Yes   Steps 1, 2 and 3 significant



   Test of joint significance   Yes   Paths a and b significant



   z test of ab product         No    se=.802, z=1.95, p=.051
                                       95% CI = -.01 to 3.13


   Empirical-M test             Yes   95% CI = .19 to 3.32



   BC parametric bootstrap      Yes   95% CI = .31 to 3.57
Cross-level and upper-level
mediation model [2→(1 & 2) →1]
Model A                                                    Model B

                                                    u0 j                              Mediator
                                                                                     CLUSTER                                    '
                                                                                                                               u0 j
                       γ01
                                                                             γ’01
                                  Mediator
                                 CLUSTER
          Treatment                                          Treatment                                            Outcome
          CLUSTER                                            CLUSTER                                              CLUSTER




                                 Mediator                                            Avg M           Mediator
          Treatment                                         Treatment                                             Outcome



                                 Mediator                                                            Mediator
                                 INDIVIDUAL                                                          INDIVIDUAL
                                                                                                                  Outcome
                                                                                                                  INDIVIDUAL




      M ij   0 j  rij ,                    rij
                                                           Yij   0 j   Mij  r ij
                                                                         '     '                 '                             rij'
                                                                                1j

       0 j   00   01T j  u0 j                                                             
                                                            0 j   00   01 T j   02 AveM j  u0 j
                                                                      
                                                            1 j   10
 Cross-level and upper-level
 mediation model: Results
Path a is the same as in the prior model. For the b and c’
paths:




   Final estimation of fixed effects:
   ----------------------------------------------------------------------------
                                         Standard             Approx.
       Fixed Effect        Coefficient   Error      T-ratio   d.f.     P-value
   ----------------------------------------------------------------------------
   For        INTRCPT1, B0
       INTRCPT2, G00         35.095622   1.047773    33.495        11    0.000
              T, G01          2.761188   1.602238     1.723        11    0.112
         M2_AVE, G02         -0.041278   0.363535    -0.114        11    0.912
   For        M2 slope, B1
       INTRCPT2, G10          0.600111   0.160566     3.737        80    0.001
   ----------------------------------------------------------------------------
  Cross-level and upper-level mediation model
                 [2→(1 & 2) →1]
Model A                                   Model B

                                   u0 j                         Mediator
                                                               CLUSTER                                '
                                                                                                     u0 j
                       Mediator

          Treatment
                      CLUSTER
                                           Treatment
                                                       2.761                            Outcome
          CLUSTER                          CLUSTER                                      CLUSTER




                      Mediator                                 Avg M       Mediator
          Treatment                       Treatment                                     Outcome



                      Mediator                                             Mediator
                      INDIVIDUAL                                           INDIVIDUAL
                                                                                        Outcome
                                   rij'                                                 INDIVIDUAL      rij'


   abind  = (2.643)(.600) = 1.586
   abcluster = (2.643)(-.041) = -.109
   Total indirect effect = 1.586 – 0.109 = 1.477
   Total effect = 1.477+2.761 = 4.238
    Cross-level and upper-level mediation model
      [2→(1 & 2) →1] Group-mean centered M
Model A                                   Model B

                                   u0 j                         Mediator
                                                               CLUSTER                                '
                                                                                                     u0 j
                       Mediator

          Treatment
                      CLUSTER
                                           Treatment
                                                       2.761                            Outcome
          CLUSTER                          CLUSTER                                      CLUSTER




                      Mediator                                 Avg M       Mediator
          Treatment                       Treatment                                     Outcome



                      Mediator                                             Mediator
                      INDIVIDUAL                                           INDIVIDUAL
                                                                                        Outcome
                                   rij'                                                 INDIVIDUAL      rij'


 If the level one predictor had been group-mean centered, then
  the L2 path would have been 0.559 not -0.041.
 This path would be interpreted as the sum of the average
  individual and contextual effects of M.
 Under grand-mean centering, the path represents the unique
  contextual effect.
Cross- and upper-level mediation
model: Results at the individual level
   Causal steps approach        Yes   Steps 1, 2 and 3 significant



   Test of joint significance   Yes   Paths a and b significant



   z test of ab product         No    se=.886, z=1.79, p=.073
                                       95% CI = -.15 to 3.32


   Empirical-M test             Yes   95% CI = .19 to 3.44



   BC parametric bootstrap      ?     Not yet programmed
Brief review of advanced issues

   Multisite / randomized blocks (1→1 →1)
     More   complicated!
   Testing mediation in 3-level models
   Including multiple mediators
   Examining moderated mediation
   Dichotomous or polytomous outcomes
   Measurement error in mediation models
Notes on software

   HLM,SPSS
     Plug results into PRODCLIN
   SAS (PROC MIXED)
       See handout
       Can use Stapleton’s macros for bootstrapping
   MLwiN, MPlus
     Have limited bootstrapping capacity but still
      have to summarize results
   SEM software
     Provide test of  but using Sobel.
tasha.beretvas@mail.utexas.edu

						
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