The HPLMIXED Procedure

Formulation of the Mixed Model

The previous general linear model is certainly a useful one (Searle 1971), and it is the one fitted by the GLM procedure. However, many times the distributional assumption about epsilon is too restrictive. The mixed model extends the general linear model by allowing a more flexible specification of the covariance matrix of epsilon. In other words, it allows for both correlation and heterogeneous variances, although you still assume normality.

The mixed model is written as

bold y equals bold upper X bold-italic beta plus bold upper Z bold-italic gamma plus bold-italic epsilon

where everything is the same as in the general linear model except for the addition of the known design matrix, bold upper Z, and the vector of unknown random-effects parameters, bold-italic gamma. The matrix bold upper Z can contain either continuous or dummy variables, just like bold upper X. The name mixed model comes from the fact that the model contains both fixed-effects parameters, bold-italic beta, and random-effects parameters, bold-italic gamma. See Henderson (1990) and Searle, Casella, and McCulloch (1992) for historical developments of the mixed model.

A key assumption in the foregoing analysis is that bold-italic gamma and bold-italic epsilon are normally distributed with

StartLayout 1st Row 1st Column normal upper E StartBinomialOrMatrix bold-italic gamma Choose bold-italic epsilon EndBinomialOrMatrix 2nd Column equals StartBinomialOrMatrix bold 0 Choose bold 0 EndBinomialOrMatrix 2nd Row 1st Column normal upper V normal a normal r StartBinomialOrMatrix bold-italic gamma Choose bold-italic epsilon EndBinomialOrMatrix 2nd Column equals Start 2 By 2 Matrix 1st Row 1st Column bold upper G 2nd Column bold 0 2nd Row 1st Column bold 0 2nd Column bold upper R EndMatrix EndLayout

Therefore, the variance of bold y is bold upper V equals bold upper Z bold upper G bold upper Z prime plus bold upper R. You can model bold upper V by setting up the random-effects design matrix bold upper Z and by specifying covariance structures for bold upper G and bold upper R.

Note that this is a general specification of the mixed model, in contrast to many texts and articles that discuss only simple random effects. Simple random effects are a special case of the general specification with bold upper Z containing dummy variables, bold upper G containing variance components in a diagonal structure, and bold upper R equals sigma squared bold upper I Subscript n, where bold upper I Subscript n denotes the n times n identity matrix. The general linear model is a further special case with bold upper Z equals bold 0 and bold upper R equals sigma squared bold upper I Subscript n.

The following two examples illustrate the most common formulations of the general linear mixed model.

Example: Growth Curve with Compound Symmetry

Suppose that you have three growth curve measurements for s individuals and that you want to fit an overall linear trend in time. Your bold upper X matrix is as follows:

bold upper X equals Start 7 By 2 Matrix 1st Row 1st Column 1 2nd Column 1 2nd Row 1st Column 1 2nd Column 2 3rd Row 1st Column 1 2nd Column 3 4th Row 1st Column vertical-ellipsis 2nd Column vertical-ellipsis 5th Row 1st Column 1 2nd Column 1 6th Row 1st Column 1 2nd Column 2 7th Row 1st Column 1 2nd Column 3 EndMatrix

The first column (coded entirely with 1s) fits an intercept, and the second column (coded with series of 1 comma 2 comma 3) fits a slope. Here, n equals 3 s and p equals 2.

Suppose further that you want to introduce a common correlation among the observations from a single individual, with correlation being the same for all individuals. One way of setting this up in the general mixed model is to eliminate the bold upper Z and bold upper G matrices and let the bold upper R matrix be block-diagonal with blocks corresponding to the individuals and with each block having the compound-symmetry structure. This structure has two unknown parameters, one modeling a common covariance and the other modeling a residual variance. The form for bold upper R would then be

bold upper R equals Start 7 By 7 Matrix 1st Row 1st Column sigma 1 squared plus sigma squared 2nd Column sigma 1 squared 3rd Column sigma 1 squared 4th Column Blank 5th Column Blank 6th Column Blank 7th Column Blank 2nd Row 1st Column sigma 1 squared 2nd Column sigma 1 squared plus sigma squared 3rd Column sigma 1 squared 4th Column Blank 5th Column Blank 6th Column Blank 7th Column Blank 3rd Row 1st Column sigma 1 squared 2nd Column sigma 1 squared 3rd Column sigma 1 squared plus sigma squared 4th Column Blank 5th Column Blank 6th Column Blank 7th Column Blank 4th Row 1st Column Blank 2nd Column Blank 3rd Column Blank 4th Column down-right-diagonal-ellipsis 5th Column Blank 6th Column Blank 7th Column Blank 5th Row 1st Column Blank 2nd Column Blank 3rd Column Blank 4th Column Blank 5th Column sigma 1 squared plus sigma squared 6th Column sigma 1 squared 7th Column sigma 1 squared 6th Row 1st Column Blank 2nd Column Blank 3rd Column Blank 4th Column Blank 5th Column sigma 1 squared 6th Column sigma 1 squared plus sigma squared 7th Column sigma 1 squared 7th Row 1st Column Blank 2nd Column Blank 3rd Column Blank 4th Column Blank 5th Column sigma 1 squared 6th Column sigma 1 squared 7th Column sigma 1 squared plus sigma squared EndMatrix

where blanks denote zeros. There are 3 s rows and columns altogether, and the common correlation is sigma 1 squared slash left-parenthesis sigma 1 squared plus sigma squared right-parenthesis.

The following PROC HPLMIXED statements fit this model:

proc hplmixed;
   class indiv;
   model y = time;
   repeated morder/ type=cs subject=indiv;
run;

Here, INDIV is a classification variable that indexes individuals. The MODEL statement fits a straight line for TIME ; the intercept is fit by default just as in PROC GLM. The REPEATED statement models the bold upper R matrix: TYPE=CS specifies the compound symmetry structure, and SUBJECT=INDIV specifies the blocks of bold upper R, and MORDER is the repeated effect that records the order of the measurements for each individual.

An alternative way of specifying the common intra-individual correlation is to let

StartLayout 1st Row 1st Column bold upper Z 2nd Column equals Start 10 By 4 Matrix 1st Row 1st Column 1 2nd Column Blank 3rd Column Blank 4th Column Blank 2nd Row 1st Column 1 2nd Column Blank 3rd Column Blank 4th Column Blank 3rd Row 1st Column 1 2nd Column Blank 3rd Column Blank 4th Column Blank 4th Row 1st Column Blank 2nd Column 1 3rd Column Blank 4th Column Blank 5th Row 1st Column Blank 2nd Column 1 3rd Column Blank 4th Column Blank 6th Row 1st Column Blank 2nd Column 1 3rd Column Blank 4th Column Blank 7th Row 1st Column Blank 2nd Column Blank 3rd Column down-right-diagonal-ellipsis 4th Column Blank 8th Row 1st Column Blank 2nd Column Blank 3rd Column Blank 4th Column 1 9th Row 1st Column Blank 2nd Column Blank 3rd Column Blank 4th Column 1 10th Row 1st Column Blank 2nd Column Blank 3rd Column Blank 4th Column 1 EndMatrix 2nd Row 1st Column bold upper G 2nd Column equals Start 4 By 4 Matrix 1st Row 1st Column sigma 1 squared 2nd Column Blank 3rd Column Blank 4th Column Blank 2nd Row 1st Column Blank 2nd Column sigma 1 squared 3rd Column Blank 4th Column Blank 3rd Row 1st Column Blank 2nd Column Blank 3rd Column down-right-diagonal-ellipsis 4th Column Blank 4th Row 1st Column Blank 2nd Column Blank 3rd Column Blank 4th Column sigma 1 squared EndMatrix EndLayout

and bold upper R equals sigma squared bold upper I Subscript n. The bold upper Z matrix has 3 s rows and s columns, and bold upper G is s times s.

You can set up this model in PROC HPLMIXED in two different but equivalent ways:

proc hplmixed;
   class indiv;
   model y = time;
   random indiv;
run;

proc hplmixed;
   class indiv;
   model y = time;
   random intercept / subject=indiv;
run;

Both of these specifications fit the same model as the previous one that used the REPEATED statement. However, the RANDOM specifications constrain the correlation to be positive, whereas the REPEATED specification leaves the correlation unconstrained.

Example: Split-Plot Design

The split-plot design involves two experimental treatment factors, A and B, and two different sizes of experimental units to which they are applied (Winer 1971; Snedecor and Cochran 1980; Milliken and Johnson 1992; Steel, Torrie, and Dickey 1997). The levels of A are randomly assigned to the larger-sized experimental units, called whole plots, whereas the levels of B are assigned to the smaller-sized experimental units, the subplots. The subplots are assumed to be nested within the whole plots, so that a whole plot consists of a cluster of subplots and a level of A is applied to the entire cluster.

Such an arrangement is often necessary by nature of the experiment; the classical example is the application of fertilizer to large plots of land and different crop varieties planted in subdivisions of the large plots. For this example, fertilizer is the whole-plot factor A and variety is the subplot factor B.

The first example is a split-plot design for which the whole plots are arranged in a randomized block design. The appropriate PROC HPLMIXED statements are as follows:

proc hplmixed;
   class a b block;
   model y = a b a*b;
   random block a*block;
run;

Here

bold upper R equals sigma squared bold upper I 24

and bold upper X, bold upper Z, and bold upper G have the following form:

bold upper X equals Start 13 By 12 Matrix 1st Row 1st Column 1 2nd Column 1 3rd Column Blank 4th Column Blank 5th Column 1 6th Column Blank 7th Column 1 8th Column Blank 9th Column Blank 10th Column Blank 11th Column Blank 12th Column Blank 2nd Row 1st Column 1 2nd Column 1 3rd Column Blank 4th Column Blank 5th Column Blank 6th Column 1 7th Column Blank 8th Column 1 9th Column Blank 10th Column Blank 11th Column Blank 12th Column Blank 3rd Row 1st Column 1 2nd Column Blank 3rd Column 1 4th Column Blank 5th Column 1 6th Column Blank 7th Column Blank 8th Column Blank 9th Column 1 10th Column Blank 11th Column Blank 12th Column Blank 4th Row 1st Column 1 2nd Column Blank 3rd Column 1 4th Column Blank 5th Column Blank 6th Column 1 7th Column Blank 8th Column Blank 9th Column Blank 10th Column 1 11th Column Blank 12th Column Blank 5th Row 1st Column 1 2nd Column Blank 3rd Column Blank 4th Column 1 5th Column 1 6th Column Blank 7th Column Blank 8th Column Blank 9th Column Blank 10th Column Blank 11th Column 1 12th Column Blank 6th Row 1st Column 1 2nd Column Blank 3rd Column Blank 4th Column 1 5th Column Blank 6th Column 1 7th Column Blank 8th Column Blank 9th Column Blank 10th Column Blank 11th Column Blank 12th Column 1 7th Row 1st Column vertical-ellipsis 2nd Column Blank 3rd Column vertical-ellipsis 4th Column Blank 5th Column vertical-ellipsis 6th Column Blank 7th Column Blank 8th Column Blank 9th Column Blank 10th Column vertical-ellipsis 8th Row 1st Column 1 2nd Column 1 3rd Column Blank 4th Column Blank 5th Column 1 6th Column Blank 7th Column 1 8th Column Blank 9th Column Blank 10th Column Blank 11th Column Blank 12th Column Blank 9th Row 1st Column 1 2nd Column 1 3rd Column Blank 4th Column Blank 5th Column Blank 6th Column 1 7th Column Blank 8th Column 1 9th Column Blank 10th Column Blank 11th Column Blank 12th Column Blank 10th Row 1st Column 1 2nd Column Blank 3rd Column 1 4th Column Blank 5th Column 1 6th Column Blank 7th Column Blank 8th Column Blank 9th Column 1 10th Column Blank 11th Column Blank 12th Column Blank 11th Row 1st Column 1 2nd Column Blank 3rd Column 1 4th Column Blank 5th Column Blank 6th Column 1 7th Column Blank 8th Column Blank 9th Column Blank 10th Column 1 11th Column Blank 12th Column Blank 12th Row 1st Column 1 2nd Column Blank 3rd Column Blank 4th Column 1 5th Column 1 6th Column Blank 7th Column Blank 8th Column Blank 9th Column Blank 10th Column Blank 11th Column 1 12th Column Blank 13th Row 1st Column 1 2nd Column Blank 3rd Column Blank 4th Column 1 5th Column Blank 6th Column 1 7th Column Blank 8th Column Blank 9th Column Blank 10th Column Blank 11th Column Blank 12th Column 1 EndMatrix
bold upper Z equals Start 24 By 16 Matrix 1st Row 1st Column 1 2nd Column Blank 3rd Column Blank 4th Column Blank 5th Column 1 6th Column Blank 7th Column Blank 8th Column Blank 9th Column Blank 10th Column Blank 11th Column Blank 12th Column Blank 13th Column Blank 14th Column Blank 15th Column Blank 16th Column Blank 2nd Row 1st Column 1 2nd Column Blank 3rd Column Blank 4th Column Blank 5th Column 1 6th Column Blank 7th Column Blank 8th Column Blank 9th Column Blank 10th Column Blank 11th Column Blank 12th Column Blank 13th Column Blank 14th Column Blank 15th Column Blank 16th Column Blank 3rd Row 1st Column 1 2nd Column Blank 3rd Column Blank 4th Column Blank 5th Column Blank 6th Column 1 7th Column Blank 8th Column Blank 9th Column Blank 10th Column Blank 11th Column Blank 12th Column Blank 13th Column Blank 14th Column Blank 15th Column Blank 16th Column Blank 4th Row 1st Column 1 2nd Column Blank 3rd Column Blank 4th Column Blank 5th Column Blank 6th Column 1 7th Column Blank 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Column Blank 6th Column Blank 7th Column Blank 8th Column Blank 9th Column Blank 10th Column Blank 11th Column Blank 12th Column Blank 13th Column Blank 14th Column Blank 15th Column 1 16th Column Blank 23rd Row 1st Column Blank 2nd Column Blank 3rd Column Blank 4th Column 1 5th Column Blank 6th Column Blank 7th Column Blank 8th Column Blank 9th Column Blank 10th Column Blank 11th Column Blank 12th Column Blank 13th Column Blank 14th Column Blank 15th Column Blank 16th Column 1 24th Row 1st Column Blank 2nd Column Blank 3rd Column Blank 4th Column 1 5th Column Blank 6th Column Blank 7th Column Blank 8th Column Blank 9th Column Blank 10th Column Blank 11th Column Blank 12th Column Blank 13th Column Blank 14th Column Blank 15th Column Blank 16th Column 1 EndMatrix
bold upper G equals Start 8 By 8 Matrix 1st Row 1st Column sigma Subscript upper B Superscript 2 Baseline 2nd Column Blank 3rd Column Blank 4th Column Blank 5th Column Blank 6th Column Blank 7th Column Blank 8th Column Blank 2nd Row 1st Column Blank 2nd Column sigma Subscript upper B Superscript 2 Baseline 3rd Column Blank 4th Column Blank 5th Column Blank 6th Column Blank 7th Column Blank 8th Column Blank 3rd Row 1st Column Blank 2nd Column Blank 3rd Column sigma Subscript upper B Superscript 2 Baseline 4th Column Blank 5th Column Blank 6th Column Blank 7th Column Blank 8th Column Blank 4th Row 1st Column Blank 2nd Column Blank 3rd Column Blank 4th Column sigma Subscript upper B Superscript 2 Baseline 5th Column Blank 6th Column Blank 7th Column Blank 8th Column Blank 5th Row 1st Column Blank 2nd Column Blank 3rd Column Blank 4th Column Blank 5th Column sigma Subscript upper A upper B Superscript 2 Baseline 6th Column Blank 7th Column Blank 8th Column Blank 6th Row 1st Column Blank 2nd Column Blank 3rd Column Blank 4th Column Blank 5th Column Blank 6th Column sigma Subscript upper A upper B Superscript 2 Baseline 7th Column Blank 8th Column Blank 7th Row 1st Column Blank 2nd Column Blank 3rd Column Blank 4th Column Blank 5th Column Blank 6th Column Blank 7th Column down-right-diagonal-ellipsis 8th Column Blank 8th Row 1st Column Blank 2nd Column Blank 3rd Column Blank 4th Column Blank 5th Column Blank 6th Column Blank 7th Column Blank 8th Column sigma Subscript upper A upper B Superscript 2 EndMatrix

where sigma Subscript upper B Superscript 2 is the variance component for Block and sigma Subscript upper A upper B Superscript 2 is the variance component for A*Block. Changing the RANDOM statement as follows fits the same model, but with bold upper Z and bold upper G sorted differently:

random int a / subject=block;
StartLayout 1st Row 1st Column bold upper Z 2nd Column equals Start 24 By 16 Matrix 1st Row 1st Column 1 2nd Column 1 3rd Column Blank 4th Column Blank 5th Column Blank 6th Column Blank 7th Column Blank 8th Column Blank 9th Column Blank 10th Column Blank 11th Column Blank 12th Column Blank 13th Column Blank 14th Column Blank 15th Column Blank 16th Column Blank 2nd Row 1st Column 1 2nd Column 1 3rd Column Blank 4th Column Blank 5th Column Blank 6th Column Blank 7th Column Blank 8th Column Blank 9th Column Blank 10th Column Blank 11th Column Blank 12th Column Blank 13th Column Blank 14th Column Blank 15th Column Blank 16th Column Blank 3rd Row 1st Column 1 2nd Column Blank 3rd Column 1 4th Column Blank 5th Column Blank 6th Column Blank 7th Column Blank 8th Column Blank 9th Column Blank 10th Column Blank 11th Column Blank 12th Column Blank 13th Column Blank 14th Column Blank 15th Column Blank 16th Column Blank 4th Row 1st Column 1 2nd Column Blank 3rd Column 1 4th Column Blank 5th Column 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Column Blank 6th Column Blank 7th Column Blank 8th Column Blank 9th Column Blank 2nd Row 1st Column Blank 2nd Column sigma Subscript upper A upper B Superscript 2 Baseline 3rd Column Blank 4th Column Blank 5th Column Blank 6th Column Blank 7th Column Blank 8th Column Blank 9th Column Blank 3rd Row 1st Column Blank 2nd Column Blank 3rd Column sigma Subscript upper A upper B Superscript 2 Baseline 4th Column Blank 5th Column Blank 6th Column Blank 7th Column Blank 8th Column Blank 9th Column Blank 4th Row 1st Column Blank 2nd Column Blank 3rd Column Blank 4th Column sigma Subscript upper A upper B Superscript 2 Baseline 5th Column Blank 6th Column Blank 7th Column Blank 8th Column Blank 9th Column Blank 5th Row 1st Column Blank 2nd Column Blank 3rd Column Blank 4th Column Blank 5th Column down-right-diagonal-ellipsis 6th Column Blank 7th Column Blank 8th Column Blank 9th Column Blank 10th Column Blank 6th Row 1st Column Blank 2nd Column Blank 3rd Column Blank 4th Column Blank 5th Column Blank 6th Column sigma Subscript upper B Superscript 2 Baseline 7th Column Blank 8th Column Blank 9th Column Blank 7th Row 1st Column Blank 2nd Column Blank 3rd Column Blank 4th Column Blank 5th Column Blank 6th Column Blank 7th Column sigma Subscript upper A upper B Superscript 2 Baseline 8th Column Blank 9th Column Blank 8th Row 1st Column Blank 2nd Column Blank 3rd Column Blank 4th Column Blank 5th Column Blank 6th Column Blank 7th Column Blank 8th Column sigma Subscript upper A upper B Superscript 2 Baseline 9th Column Blank 9th Row 1st Column Blank 2nd Column Blank 3rd Column Blank 4th Column Blank 5th Column Blank 6th Column Blank 7th Column Blank 8th Column Blank 9th Column sigma Subscript upper A upper B Superscript 2 EndMatrix EndLayout
Last updated: December 09, 2022