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Examp3.1 is.

References

  1. Duchateau, L. and Janssen, P. and Rowlands, G. J. (1998).Linear Mixed Models. An Introduction with applications in Veterinary Research. International Livestock Research Institute.

See also

Author

  1. Muhammad Yaseen (myaseen208@gmail.com)

Examples

#-------------------------------------------------------------
## Example 3.1 Model 1 p-80
#-------------------------------------------------------------
# PROC MIXED DATA=ex31;
# CLASS drug dose herd;
# MODEL PCV2=drug dose(drug)/solution ddfm=satterth;
# RANDOM herd(drug);
# ESTIMATE 'Mean Samorin' intercept 1 drug 0 1 dose(drug) 0 0 1;
# ESTIMATE 'Berenil 2 doses' dose(drug) 1 -1 0;
# ESTIMATE 'Ber vs Sam at dose 1' drug 1 -1 dose(drug) 1 0 -1;
# CONTRAST 'Mean Samorin' intercept 1 drug 0 1 dose(drug) 0 0 1;
# CONTRAST 'Berenil dif 2 doses' dose(drug) 1 -1 0;
# CONTRAST 'Ber vs Sam at dose 1' drug 1 -1 dose(drug) 1 0 -l;
# CONTRAST 'some difference' drug 1 -1 dose(drug) 0.5 0.5 -1,
#           drug 0 0 dose(drug) 1 -1 0;
# LSMEANS dose(drug);
# RUN;

 library(lmerTest)
 str(ex31)
#> 'data.frame':	38 obs. of  6 variables:
#>  $ herd     : int  1 1 1 1 1 1 1 1 1 2 ...
#>  $ animal_id: int  667 1003 1177 227 241 271 44 48 233 1368 ...
#>  $ PCV1     : int  17 22 20 22 22 18 22 21 18 18 ...
#>  $ PCV2     : int  28 23 28 25 23 18 27 20 30 20 ...
#>  $ dose     : int  1 1 1 2 2 2 1 1 1 1 ...
#>  $ drug     : Factor w/ 2 levels "BERENIL","SAMORIN": 1 1 1 1 1 1 2 2 2 1 ...
 ex31 <-
   ex31 |>
   collapse::fmutate(
     herd1 = factor(herd),
     drug1 = factor(drug),
     dose1 = factor(dose),
     ber = as.integer(drug == "BERENIL"),
     ber1 = as.integer(drug == "BERENIL" & dose == 1L),
     pcv_ber1 = PCV1 * as.integer(drug == "BERENIL" & dose == 1L),
     pcv_ber2 = PCV1 * as.integer(drug == "BERENIL" & dose == 2L)
   )

 fm3.1 <-
  lmerTest::lmer(
         formula    = PCV2 ~ drug1 + dose1:drug1 + (1|herd1:drug1)
       , data       = ex31
       , REML       = TRUE
       , control    = lmerControl()
       , start      = NULL
       , verbose    = 0L
    #  , subset
    #  , weights
    #  , na.action
    #  , offset
       , contrasts  = list(dose1 = "contr.SAS", drug1 = "contr.SAS")
       , devFunOnly = FALSE
    #  , ...
       )
#> fixed-effect model matrix is rank deficient so dropping 1 column / coefficient
#> fixed-effect model matrix is rank deficient so dropping 1 column / coefficient
 if (requireNamespace("report", quietly = TRUE)) {
   fm3.1 |>
     report::report()
 }
#> fixed-effect model matrix is rank deficient so dropping 1 column / coefficient
#> fixed-effect model matrix is rank deficient so dropping 1 column / coefficient
#> fixed-effect model matrix is rank deficient so dropping 1 column / coefficient
#> fixed-effect model matrix is rank deficient so dropping 1 column / coefficient
#> We fitted a linear mixed model (estimated using REML and nloptwrap optimizer)
#> to predict PCV2 with drug1 and dose1 (formula: PCV2 ~ drug1 + dose1:drug1). The
#> model included herd1 as random effects (formula: ~1 | herd1:drug1). The model's
#> total explanatory power is weak (conditional R2 = 0.12) and the part related to
#> the fixed effects alone (marginal R2) is of 0.06. The model's intercept,
#> corresponding to drug1 = BERENIL and dose1 = 1, is at 24.17 (95% CI [22.05,
#> 26.28], t(33) = 23.28, p < .001). Within this model:
#> 
#>   - The effect of drug1 [BERENIL] is statistically non-significant and positive
#> (beta = 1.10, 95% CI [-1.80, 4.00], t(33) = 0.77, p = 0.445; Std. beta = 0.32,
#> 95% CI [-0.53, 1.17])
#>   - The effect of drug1 [BERENIL] × dose11 is statistically non-significant and
#> negative (beta = -2.10, 95% CI [-4.75, 0.55], t(33) = -1.61, p = 0.116; Std.
#> beta = -0.61, 95% CI [-1.39, 0.16])
#> 
#> Standardized parameters were obtained by fitting the model on a standardized
#> version of the dataset. 95% Confidence Intervals (CIs) and p-values were
#> computed using a Wald t-distribution approximation.
 if (requireNamespace("emmeans", quietly = TRUE)) {
   emm3.1 <- emmeans::emmeans(fm3.1, ~ dose1 | drug1, lmer.df = "asymptotic")
   print(emm3.1)
   print(emmeans::contrast(emm3.1, method = "pairwise"))
 }
#> NOTE: A nesting structure was detected in the fitted model:
#>     dose1 %in% drug1
#> drug1 = BERENIL:
#>  dose1 emmean    SE  df asymp.LCL asymp.UCL
#>  1       23.2 1.040 Inf      21.1      25.2
#>  2       25.3 0.977 Inf      23.4      27.2
#> 
#> drug1 = SAMORIN:
#>  dose1 emmean    SE  df asymp.LCL asymp.UCL
#>  1       24.2 1.040 Inf      22.1      26.2
#> 
#> Degrees-of-freedom method: asymptotic 
#> Confidence level used: 0.95 
#> drug1 = BERENIL:
#>  contrast        estimate  SE  df z.ratio p.value
#>  dose11 - dose12     -2.1 1.3 Inf  -1.612  0.1069
#> 
#> drug1 = SAMORIN:
#>  contrast        estimate  SE  df z.ratio p.value
#>  (nothing)         nonEst  NA  NA      NA      NA
#> 
#> Degrees-of-freedom method: asymptotic 
 summary(fm3.1)
#> Linear mixed model fit by REML. t-tests use Satterthwaite's method [
#> lmerModLmerTest]
#> Formula: PCV2 ~ drug1 + dose1:drug1 + (1 | herd1:drug1)
#>    Data: ex31
#> 
#> REML criterion at convergence: 192.1
#> 
#> Scaled residuals: 
#>      Min       1Q   Median       3Q      Max 
#> -2.19435 -0.64365  0.04272  0.47738  1.69413 
#> 
#> Random effects:
#>  Groups      Name        Variance Std.Dev.
#>  herd1:drug1 (Intercept)  0.6682  0.8175  
#>  Residual                10.9299  3.3060  
#> Number of obs: 38, groups:  herd1:drug1, 8
#> 
#> Fixed effects:
#>                     Estimate Std. Error     df t value Pr(>|t|)    
#> (Intercept)           24.167      1.038 15.358  23.277 2.14e-13 ***
#> drug1BERENIL           1.102      1.426 13.734   0.773    0.453    
#> drug1BERENIL:dose11   -2.102      1.303 31.520  -1.612    0.117    
#> ---
#> Signif. codes:  0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1
#> 
#> Correlation of Fixed Effects:
#>             (Intr) dr1BERENIL
#> drg1BERENIL -0.728           
#> d1BERENIL:1  0.000 -0.424    
#> fit warnings:
#> fixed-effect model matrix is rank deficient so dropping 1 column / coefficient
 anova(object = fm3.1, ddf = "Satterthwaite")
#> Missing cells for: drug1SAMORIN:dose12.  
#> Interpret type III hypotheses with care.
#> Type III Analysis of Variance Table with Satterthwaite's method
#>              Sum Sq Mean Sq NumDF  DenDF F value Pr(>F)
#> drug1        5.0701  5.0701     1 15.358  0.4639 0.5060
#> drug1:dose1 28.4190 28.4190     1 31.520  2.6001 0.1168
 lsmeansLT(model = fm3.1, test.effs = "dose1:drug1")
#> Least Squares Means table:
#> 
#>                     Estimate Std. Error   df t value    lower    upper
#> drug1BERENIL        24.21745    0.76923  5.3  31.483 22.26991 26.16499
#> drug1SAMORIN              NA         NA   NA      NA       NA       NA
#> drug1BERENIL:dose11 23.16667    1.03821 15.4  22.314 20.95825 25.37508
#> drug1SAMORIN:dose11 24.16667    1.03821 15.4  23.277 21.95825 26.37508
#> drug1BERENIL:dose12 25.26823    0.97716 12.1  25.859 23.14188 27.39459
#> drug1SAMORIN:dose12       NA         NA   NA      NA       NA       NA
#>                      Pr(>|t|)    
#> drug1BERENIL        3.348e-07 ***
#> drug1SAMORIN               NA    
#> drug1BERENIL:dose11 4.024e-13 ***
#> drug1SAMORIN:dose11 2.140e-13 ***
#> drug1BERENIL:dose12 5.494e-12 ***
#> drug1SAMORIN:dose12        NA    
#> ---
#> Signif. codes:  0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1
#> 
#>   Confidence level: 95%
#>   Degrees of freedom method: Satterthwaite 

#-------------------------------------------------------------
## Example 3.1 Model 2 p-84
#-------------------------------------------------------------
# PROC MIXED DATA=ex31;
# CLASS drug dose herd;
# MODEL PCV2=PCV1 drug dose(drug)/solution ddfm=satterth;
# RANDOM herd(drug);
# RUN;

 fm3.2 <-
  lmerTest::lmer(
         formula    = PCV2 ~ PCV1 + drug1 + dose1:drug1 + (1|herd1:drug1)
       , data       = ex31
       , REML       = TRUE
       , control    = lmerControl()
       , start      = NULL
       , verbose    = 0L
    #  , subset
    #  , weights
    #  , na.action
    #  , offset
       , contrasts  = list(dose1 = "contr.SAS", drug1 = "contr.SAS")
       , devFunOnly = FALSE
    #  , ...
       )
#> fixed-effect model matrix is rank deficient so dropping 1 column / coefficient
#> fixed-effect model matrix is rank deficient so dropping 1 column / coefficient
 if (requireNamespace("report", quietly = TRUE)) {
   fm3.2 |>
     report::report()
 }
#> fixed-effect model matrix is rank deficient so dropping 1 column / coefficient
#> fixed-effect model matrix is rank deficient so dropping 1 column / coefficient
#> fixed-effect model matrix is rank deficient so dropping 1 column / coefficient
#> fixed-effect model matrix is rank deficient so dropping 1 column / coefficient
#> We fitted a linear mixed model (estimated using REML and nloptwrap optimizer)
#> to predict PCV2 with PCV1, drug1 and dose1 (formula: PCV2 ~ PCV1 + drug1 +
#> dose1:drug1). The model included herd1 as random effects (formula: ~1 |
#> herd1:drug1). The model's total explanatory power is weak (conditional R2 =
#> 0.11) and the part related to the fixed effects alone (marginal R2) is of 0.06.
#> The model's intercept, corresponding to PCV1 = 0, drug1 = BERENIL and dose1 =
#> 1, is at 23.64 (95% CI [11.28, 36.00], t(32) = 3.90, p < .001). Within this
#> model:
#> 
#>   - The effect of PCV1 is statistically non-significant and positive (beta =
#> 0.03, 95% CI [-0.57, 0.62], t(32) = 0.09, p = 0.930; Std. beta = 0.01, 95% CI
#> [-0.33, 0.36])
#>   - The effect of drug1 [BERENIL] is statistically non-significant and positive
#> (beta = 1.13, 95% CI [-1.85, 4.12], t(32) = 0.77, p = 0.446; Std. beta = 0.33,
#> 95% CI [-0.54, 1.20])
#>   - The effect of drug1 [BERENIL] × dose11 is statistically non-significant and
#> negative (beta = -2.13, 95% CI [-4.90, 0.63], t(32) = -1.57, p = 0.126; Std.
#> beta = -0.62, 95% CI [-1.43, 0.18])
#> 
#> Standardized parameters were obtained by fitting the model on a standardized
#> version of the dataset. 95% Confidence Intervals (CIs) and p-values were
#> computed using a Wald t-distribution approximation.
 if (requireNamespace("emmeans", quietly = TRUE)) {
   emm3.2 <- emmeans::emmeans(fm3.2, ~ dose1 | drug1, lmer.df = "asymptotic")
   print(emm3.2)
   print(emmeans::contrast(emm3.2, method = "pairwise"))
 }
#> NOTE: A nesting structure was detected in the fitted model:
#>     dose1 %in% drug1
#> drug1 = BERENIL:
#>  dose1 emmean   SE  df asymp.LCL asymp.UCL
#>  1       23.2 1.06 Inf      21.1      25.2
#>  2       25.3 1.00 Inf      23.3      27.3
#> 
#> drug1 = SAMORIN:
#>  dose1 emmean   SE  df asymp.LCL asymp.UCL
#>  1       24.2 1.05 Inf      22.1      26.2
#> 
#> Degrees-of-freedom method: asymptotic 
#> Confidence level used: 0.95 
#> drug1 = BERENIL:
#>  contrast        estimate   SE  df z.ratio p.value
#>  dose11 - dose12    -2.13 1.36 Inf  -1.571  0.1161
#> 
#> drug1 = SAMORIN:
#>  contrast        estimate   SE  df z.ratio p.value
#>  (nothing)         nonEst   NA  NA      NA      NA
#> 
#> Degrees-of-freedom method: asymptotic 
 summary(fm3.2)
#> Linear mixed model fit by REML. t-tests use Satterthwaite's method [
#> lmerModLmerTest]
#> Formula: PCV2 ~ PCV1 + drug1 + dose1:drug1 + (1 | herd1:drug1)
#>    Data: ex31
#> 
#> REML criterion at convergence: 192.8
#> 
#> Scaled residuals: 
#>      Min       1Q   Median       3Q      Max 
#> -2.14932 -0.63140  0.05373  0.47166  1.69087 
#> 
#> Random effects:
#>  Groups      Name        Variance Std.Dev.
#>  herd1:drug1 (Intercept)  0.6391  0.7994  
#>  Residual                11.2803  3.3586  
#> Number of obs: 38, groups:  herd1:drug1, 8
#> 
#> Fixed effects:
#>                     Estimate Std. Error       df t value Pr(>|t|)    
#> (Intercept)         23.64038    6.06889 33.91516   3.895 0.000438 ***
#> PCV1                 0.02567    0.29159 33.74677   0.088 0.930362    
#> drug1BERENIL         1.13037    1.46551 13.70396   0.771 0.453615    
#> drug1BERENIL:dose11 -2.13251    1.35725 30.87596  -1.571 0.126329    
#> ---
#> Signif. codes:  0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1
#> 
#> Correlation of Fixed Effects:
#>             (Intr) PCV1   dr1BERENIL
#> PCV1        -0.985                  
#> drg1BERENIL -0.308  0.187           
#> d1BERENIL:1  0.217 -0.220 -0.450    
#> fit warnings:
#> fixed-effect model matrix is rank deficient so dropping 1 column / coefficient
 anova(object = fm3.2, ddf = "Satterthwaite")
#> Missing cells for: drug1SAMORIN:dose12.  
#> Interpret type III hypotheses with care.
#> Type III Analysis of Variance Table with Satterthwaite's method
#>              Sum Sq Mean Sq NumDF  DenDF F value Pr(>F)
#> PCV1         0.0874  0.0874     1 33.747  0.0078 0.9304
#> drug1        5.1489  5.1489     1 14.799  0.4565 0.5097
#> drug1:dose1 27.8474 27.8474     1 30.876  2.4687 0.1263
 lsmeansLT(model = fm3.2, test.effs = "herd1:drug1")
#> Least Squares Means table:
#> 
#>                     Estimate Std. Error   df t value    lower    upper
#> drug1BERENIL        24.22268    0.77398  4.9  31.296 22.22655 26.21880
#> drug1SAMORIN              NA         NA   NA      NA       NA       NA
#> drug1BERENIL:dose11 23.15642    1.05515 15.0  21.946 20.90761 25.40523
#> drug1SAMORIN:dose11 24.15856    1.05275 14.9  22.948 21.91379 26.40333
#> drug1BERENIL:dose12 25.28893    1.00290 12.0  25.216 23.10450 27.47336
#> drug1SAMORIN:dose12       NA         NA   NA      NA       NA       NA
#>                      Pr(>|t|)    
#> drug1BERENIL        7.056e-07 ***
#> drug1SAMORIN               NA    
#> drug1BERENIL:dose11 8.033e-13 ***
#> drug1SAMORIN:dose11 4.672e-13 ***
#> drug1BERENIL:dose12 8.709e-12 ***
#> drug1SAMORIN:dose12        NA    
#> ---
#> Signif. codes:  0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1
#> 
#>   Confidence level: 95%
#>   Degrees of freedom method: Satterthwaite 

#-------------------------------------------------------------
## Example 3.1 Model 3 p-86
#-------------------------------------------------------------
# PROC MIXED DATA=ex31;
# CLASS drug dose herd;
# MODEL PCV2=drug dose(drug) PCV1*dose(drug)/solution ddfm=satterth;
# RANDOM herd(drug);
# RUN;

 fm3.3 <-
  lmerTest::lmer(
         formula    = PCV2 ~ drug1 + PCV1*dose1:drug1 + (1|herd1:drug1)
       , data       = ex31
       , REML       = TRUE
       , control    = lmerControl()
       , start      = NULL
       , verbose    = 0L
    #  , subset
    #  , weights
    #  , na.action
    #  , offset
       , contrasts  = list(dose1 = "contr.SAS", drug1 = "contr.SAS")
       , devFunOnly = FALSE
    #  , ...
       )
#> fixed-effect model matrix is rank deficient so dropping 3 columns / coefficients
#> fixed-effect model matrix is rank deficient so dropping 3 columns / coefficients
 if (requireNamespace("report", quietly = TRUE)) {
   fm3.3 |>
     report::report()
 }
#> fixed-effect model matrix is rank deficient so dropping 3 columns / coefficients
#> fixed-effect model matrix is rank deficient so dropping 3 columns / coefficients
#> fixed-effect model matrix is rank deficient so dropping 3 columns / coefficients
#> fixed-effect model matrix is rank deficient so dropping 3 columns / coefficients
#> We fitted a linear mixed model (estimated using REML and nloptwrap optimizer)
#> to predict PCV2 with drug1, PCV1 and dose1 (formula: PCV2 ~ drug1 + PCV1 *
#> dose1:drug1). The model included herd1 as random effects (formula: ~1 |
#> herd1:drug1). The model's total explanatory power is moderate (conditional R2 =
#> 0.14) and the part related to the fixed effects alone (marginal R2) is of 0.09.
#> The model's intercept, corresponding to drug1 = BERENIL, PCV1 = 0 and dose1 =
#> 1, is at 33.12 (95% CI [2.67, 63.57], t(30) = 2.22, p = 0.034). Within this
#> model:
#> 
#>   - The effect of drug1 [BERENIL] is statistically non-significant and negative
#> (beta = -13.83, 95% CI [-47.83, 20.17], t(30) = -0.83, p = 0.413; Std. beta =
#> 0.34, 95% CI [-0.55, 1.22])
#>   - The effect of PCV1 is statistically non-significant and positive (beta =
#> 0.31, 95% CI [-0.46, 1.07], t(30) = 0.82, p = 0.421; Std. beta = 0.18, 95% CI
#> [-0.27, 0.62])
#>   - The effect of drug1 [BERENIL] × dose11 is statistically non-significant and
#> positive (beta = 12.13, 95% CI [-17.95, 42.21], t(30) = 0.82, p = 0.417; Std.
#> beta = -0.62, 95% CI [-1.45, 0.20])
#>   - The effect of drug1 [BERENIL] × PCV1 × dose11 is statistically
#> non-significant and negative (beta = -0.71, 95% CI [-2.18, 0.77], t(30) =
#> -0.98, p = 0.335; Std. beta = -0.41, 95% CI [-1.26, 0.44])
#>   - The effect of drug1SAMORIN × PCV1 × dose11 is statistically non-significant
#> and negative (beta = -0.74, 95% CI [-2.41, 0.93], t(30) = -0.91, p = 0.371;
#> Std. beta = -0.43, 95% CI [-1.40, 0.54])
#> 
#> Standardized parameters were obtained by fitting the model on a standardized
#> version of the dataset. 95% Confidence Intervals (CIs) and p-values were
#> computed using a Wald t-distribution approximation.
 if (requireNamespace("emmeans", quietly = TRUE)) {
   emm3.3 <- emmeans::emmeans(fm3.3, ~ dose1 | drug1, lmer.df = "asymptotic")
   print(emm3.3)
   print(emmeans::contrast(emm3.3, method = "pairwise"))
 }
#> NOTE: A nesting structure was detected in the fitted model:
#>     dose1 %in% drug1
#> NOTE: Results may be misleading due to involvement in interactions
#> drug1 = BERENIL:
#>  dose1 emmean   SE  df asymp.LCL asymp.UCL
#>  1       23.3 1.09 Inf      21.2      25.5
#>  2       25.5 1.02 Inf      23.5      27.5
#> 
#> drug1 = SAMORIN:
#>  dose1 emmean   SE  df asymp.LCL asymp.UCL
#>  1       24.3 1.08 Inf      22.2      26.4
#> 
#> Degrees-of-freedom method: asymptotic 
#> Confidence level used: 0.95 
#> drug1 = BERENIL:
#>  contrast        estimate   SE  df z.ratio p.value
#>  dose11 - dose12    -2.13 1.38 Inf  -1.548  0.1217
#> 
#> drug1 = SAMORIN:
#>  contrast        estimate   SE  df z.ratio p.value
#>  (nothing)         nonEst   NA  NA      NA      NA
#> 
#> Degrees-of-freedom method: asymptotic 
 summary(fm3.3)
#> Linear mixed model fit by REML. t-tests use Satterthwaite's method [
#> lmerModLmerTest]
#> Formula: PCV2 ~ drug1 + PCV1 * dose1:drug1 + (1 | herd1:drug1)
#>    Data: ex31
#> 
#> REML criterion at convergence: 188.8
#> 
#> Scaled residuals: 
#>      Min       1Q   Median       3Q      Max 
#> -2.03785 -0.67127  0.06847  0.62206  1.47702 
#> 
#> Random effects:
#>  Groups      Name        Variance Std.Dev.
#>  herd1:drug1 (Intercept)  0.6475  0.8046  
#>  Residual                11.4692  3.3866  
#> Number of obs: 38, groups:  herd1:drug1, 8
#> 
#> Fixed effects:
#>                          Estimate Std. Error       df t value Pr(>|t|)  
#> (Intercept)               33.1192    14.9092  31.5039   2.221   0.0336 *
#> drug1BERENIL             -13.8326    16.6481  31.8493  -0.831   0.4122  
#> PCV1                       0.3058     0.3752  30.9513   0.815   0.4212  
#> drug1BERENIL:dose11       12.1279    14.7286  31.0475   0.823   0.4165  
#> drug1BERENIL:PCV1:dose11  -0.7065     0.7218  31.0117  -0.979   0.3352  
#> drug1SAMORIN:PCV1:dose11  -0.7425     0.8167  31.8994  -0.909   0.3701  
#> ---
#> Signif. codes:  0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1
#> 
#> Correlation of Fixed Effects:
#>             (Intr) dr1BERENIL PCV1   d1BERENIL:1 d1BERENIL:P
#> drg1BERENIL -0.896                                          
#> PCV1         0.000 -0.441                                   
#> d1BERENIL:1  0.000 -0.221      0.494                        
#> d1BERENIL:P  0.000  0.227     -0.515 -0.996                 
#> d1SAMORIN:P -0.886  0.996     -0.459 -0.227       0.237     
#> fit warnings:
#> fixed-effect model matrix is rank deficient so dropping 3 columns / coefficients
 anova(object = fm3.3, ddf = "Satterthwaite")
#> Missing cells for: drug1SAMORIN:dose12, drug1SAMORIN:PCV1:dose12.  
#> Interpret type III hypotheses with care.
#> Type III Analysis of Variance Table with Satterthwaite's method
#>                   Sum Sq Mean Sq NumDF  DenDF F value Pr(>F)
#> drug1             0.0864  0.0864     1 31.982  0.0075 0.9314
#> PCV1              7.6204  7.6204     1 30.951  0.6644 0.4212
#> drug1:dose1       7.7764  7.7764     1 31.048  0.6780 0.4165
#> drug1:PCV1:dose1 16.5665  8.2832     2 31.918  0.7222 0.4934
 lsmeansLT(model = fm3.3, test.effs = "dose1:drug1")
#> Least Squares Means table:
#> 
#>                     Estimate Std. Error   df t value    lower    upper
#> drug1BERENIL        24.39310    0.79713  5.1  30.601 22.35878 26.42743
#> drug1SAMORIN              NA         NA   NA      NA       NA       NA
#> drug1BERENIL:dose11 23.32660    1.08564 15.0  21.486 21.01278 25.64041
#> drug1SAMORIN:dose11 24.30457    1.08172 14.7  22.468 21.99515 26.61400
#> drug1BERENIL:dose12 25.45960    1.02085 11.8  24.940 23.23211 27.68710
#> drug1SAMORIN:dose12       NA         NA   NA      NA       NA       NA
#>                      Pr(>|t|)    
#> drug1BERENIL        5.327e-07 ***
#> drug1SAMORIN               NA    
#> drug1BERENIL:dose11 1.096e-12 ***
#> drug1SAMORIN:dose11 8.388e-13 ***
#> drug1BERENIL:dose12 1.328e-11 ***
#> drug1SAMORIN:dose12        NA    
#> ---
#> Signif. codes:  0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1
#> 
#>   Confidence level: 95%
#>   Degrees of freedom method: Satterthwaite