Using Mixed models to analyze effects of weights on

MRD
Sri Chavva
February 27, 2019

Introduction
In this markdown, I will brief what random intercept and random slope models are and how they differ from
conventional regression models and a specific use case of a random intercept model to Dr.Rootmans ptosis
experiment.
library(readxl)

## Warning: package 'readxl' was built under R version 3.5.1

library(ggplot2)
data = read_excel('data.xlsx')
data = as.data.frame(data)

weightedEye = data[data$`Weighted (0) vs Unweighted (1)` == 0,]

Mixed effect models

So what are mixed effect models? Mixed effect models are essentially models that contain random effects and
fixed effects (more on the difference between random and fixed effects coming). Traditionally, when we create
a simple linear regression or multivariate regression model, we are trying to find beta coefficients. Lets see
how this looks on our dataset.
fixedModel = lm(MRD~`Weight (g)`,data = weightedEye)
summary(fixedModel)

##
## Call:
## lm(formula = MRD ~ `Weight (g)`, data = weightedEye)
##
## Residuals:
## Min 1Q Median 3Q Max
## -2.68434 -0.55467 -0.01001 0.45801 2.92132
##
## Coefficients:
## Estimate Std. Error t value Pr(>|t|)
## (Intercept) 3.31832 0.09549 34.751 < 2e-16 ***
## `Weight (g)` -0.52831 0.07097 -7.445 9.62e-13 ***
## ---
## Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
##
## Residual standard error: 0.955 on 311 degrees of freedom
## Multiple R-squared: 0.1513, Adjusted R-squared: 0.1485

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## F-statistic: 55.42 on 1 and 311 DF, p-value: 9.618e-13
xFixed = data.frame(`Weight (g)`= seq(0,2.4,length=20))

names(xFixed) = names(weightedEye)[5]

yFixed = predict(fixedModel,newdata = xFixed,type="response" )

prediction = data.frame(xFixed,yFixed)

prediction

## Weight..g. yFixed
## 1 0.0000000 3.318316
## 2 0.1263158 3.251582
## 3 0.2526316 3.184848
## 4 0.3789474 3.118114
## 5 0.5052632 3.051381
## 6 0.6315789 2.984647
## 7 0.7578947 2.917913
## 8 0.8842105 2.851179
## 9 1.0105263 2.784445
## 10 1.1368421 2.717711
## 11 1.2631579 2.650977
## 12 1.3894737 2.584243
## 13 1.5157895 2.517509
## 14 1.6421053 2.450775
## 15 1.7684211 2.384041
## 16 1.8947368 2.317307
## 17 2.0210526 2.250573
## 18 2.1473684 2.183839
## 19 2.2736842 2.117106
## 20 2.4000000 2.050372
ggplot(data = weightedEye,aes(x=weightedEye$`Weight (g)`,y = weightedEye$MRD)) + geom_line(aes(colour =

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weightedEye$`Subject ID`
N1 N2−15
N14 N2−16
N16 N2−17
weightedEye$MRD

4 N17 N2−18
N18 N2−2
N2 N2−3
N2−1 N2−4
N2−10 N2−5
2
N2−11 N2−6
N2−12 N2−7
N2−13 N2−8
N2−14 N2−9

0.0 0.5 1.0 1.5 2.0 2.5

weightedEye$`Weight (g)`

Now lets create a similar regression model by treating the intercept as a random effect. In effect, we will
assume every subects intercept will be different. This means, we are easing the assumption that everyone
has the same MRD at weight=0 (MRD without a weight). This is beneficial because this is probably true. . .
people probably have different baseline MRD’s and treating the intercept as a random effect allows us to
make this distinction.
library(lme4)

## Warning: package 'lme4' was built under R version 3.5.2

## Loading required package: Matrix
modelRandomIntercept = lmer(MRD~`Weight (g)`+(1|`Subject ID`),data=weightedEye)
mean(coef(modelRandomIntercept)[[1]][[1]])

## [1] 3.334749
xFixed = data.frame(`Weight (g)`= seq(0,2.4,length=20))
names(xFixed) = names(weightedEye)[5]
ggplot(data = weightedEye,aes(x=`Weight (g)`,y = MRD)) + geom_line(aes(colour = `Subject ID`)) +
geom_line(data = xFixed,aes(`Weight (g)`,mean(coef(modelRandomIntercept)[[1]][[1]]) + (`Weight (g)`)*mea

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Subject ID
N1 N2−15
N14 N2−16
N16 N2−17
4 N17 N2−18
N18 N2−2
MRD

N2 N2−3
N2−1 N2−4
N2−10 N2−5
2
N2−11 N2−6
N2−12 N2−7
N2−13 N2−8
N2−14 N2−9

0.0 0.5 1.0 1.5 2.0 2.5

Weight (g)

Ok great! So now we’ve created TWO regression lines, but they both look the same. The first one is a fixed
effect model (create through the lm function) and the second is a mixed effect model treating the intercept as
a random effect (through the lmer function). There is however a slight difference. Lets look at the intercept
of both coefficients.
cat("fixed effect model intercept : ", coef(fixedModel)[1], "\n")

## fixed effect model intercept : 3.318316

cat("mixed effect model intercept : ", mean(coef(modelRandomIntercept)[[1]][[1]]), "\n")

## mixed effect model intercept : 3.334749

A slight difference. Whether or not this difference is meaningful or significant is up to debate, but the mixed
effect model takes into account the intra-subect repeated measure correlation so we will use the mixed effect
design.

Applying splines
What we have so far is great, however we can see the that the trends are not very linear. Rather, when we
look at any specific patient, we can see the effect of adding weight on MRD is ebbed and flowed. That is,
there are some segments where adding additional weight causes a large change in MRD and some segments
where adding additional weight is not so significant. We can model these changes in intensity by using what
are known as splines.
Essentially we are creating breakpoints on our predictor variables (x-axis) and create seperate regression
models to model each of these segments. Typically we make sure that lines on each segmented are connected

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and connect smoothly (differentiable), but we’ll only worry about connecting the lines.
Choosing how many splines to implement and where to apply the breakpoints is often done through EDA or
expert judgement.
library(splines)
splinedModel = lmer(MRD~bs(`Weight (g)`,df=3)+(1|`Subject ID`),data=weightedEye)

betaCoefs = rep(0,dim(coef(splinedModel)[[1]])[2])
for(i in 1:dim(coef(splinedModel)[[1]])[2]){
betaCoefs[i] = coef(splinedModel)[[1]][[i]][1]
}
slopes = rep(0,dim(coef(splinedModel)[[1]])[2] - 1)

for(i in 1:dim(coef(splinedModel)[[1]])[2]-1){
slopes[i] = (betaCoefs[i+1])/1
}

xLine = seq(0,2.4,length=4)

yline = rep(0,length(xLine))
yline[1] = mean(coef(splinedModel)[[1]][[1]])
for(i in 1:(length(xLine)-1)){
yline[i+1] = yline[i] + slopes[i]*(2.4/3)
}
testData= data.frame(xLine,yline)

ggplot(data = weightedEye,aes(x=`Weight (g)`,y = MRD)) + geom_line(aes(colour = `Subject ID`))+

geom_line(aes(xLine,yline),data=testData,lwd=2)

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Subject ID
N1 N2−15
N14 N2−16
N16 N2−17
4 N17 N2−18
N18 N2−2
MRD

N2 N2−3
N2−1 N2−4
N2−10 N2−5
2
N2−11 N2−6
N2−12 N2−7
N2−13 N2−8
N2−14 N2−9

0.0 0.5 1.0 1.5 2.0 2.5

Weight (g)

Well! This is a major improvement to the initial linear regression model we’ve started with. Let’s look at
summary table of our mixed effect segemented linear regression model.
summary(splinedModel)

## Linear mixed model fit by REML ['lmerMod']

## Formula: MRD ~ bs(`Weight (g)`, df = 3) + (1 | `Subject ID`)
## Data: weightedEye
##
## REML criterion at convergence: 641.6
##
## Scaled residuals:
## Min 1Q Median 3Q Max
## -2.6103 -0.5475 -0.0357 0.5731 4.0295
##
## Random effects:
## Groups Name Variance Std.Dev.
## Subject ID (Intercept) 0.5833 0.7637
## Residual 0.3558 0.5965
## Number of obs: 313, groups: Subject ID, 24
##
## Fixed effects:
## Estimate Std. Error t value
## (Intercept) 3.4910 0.1788 19.524
## bs(`Weight (g)`, df = 3)1 -1.1067 0.2862 -3.867
## bs(`Weight (g)`, df = 3)2 -0.8227 0.2344 -3.510
## bs(`Weight (g)`, df = 3)3 -1.5303 0.1504 -10.172

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##
## Correlation of Fixed Effects:
## (Intr) b(`W()`,d=3)1 b(`W()`,d=3)2
## b(`W()`,d=3)1 -0.357
## b(`W()`,d=3)2 -0.032 -0.480
## b(`W()`,d=3)3 -0.323 0.656 -0.399
All the slope coefficients are negative and the intercept seems to make sense. We can see that the area of
highest impact on MRD is in the 3rd (and last) segement (from 1.6 to 2.4 grams). This makes sense because
this is probably where most people face their natural breakpoint (the weight where people can not handle
more weight) and thus the reseracher chose to end the experiment with 2.4 gram weights.

Conclusion
We can see that inducing random effects and splines in our data improves the accuracy our our model
substancially. From here on out, we can add additional predictors and add random slopes. Give it a try!