other robust regression models that, like quantile regression, use an objective different from minimizing the sum of squared errors (Venables & Ripley, 2003)
semiparametric models based on the ranks of \(Y\), such as the Cox proportional hazards model and the proportional odds ordinal logistic model
cumulative probability models (often called cumulative link models) which are semiparametric models from a wider class of families than the logistic
Semiparametric models that treat \(Y\) as ordinal but not interval-scaled have many advantages including robustness and freedom of distributional assumptions for \(Y\) conditional on any given set of predictors. Advantages are demonstrated in a case study of a cumulative probability ordinal model. Some of the results are compared to quantile regression and OLS. Many of the methods used in the case study also apply to ordinary linear models.
B
15.1 Dataset and Descriptive Statistics
Diabetes Mellitus (DM) type II (adult onset diabetes) is strongly associated with obesity
Primary laboratory test for diabetes: glycosylated hemoglobin (\(\text{HbA}_{1c}\)), also called glycated hemoglobin, glycohemoglobin, or hemoglobin \(A_{1c}\).
\(\text{HbA}_{1c}\) reflects average blood glucose for the preceding 60 to 90 days
\(\text{HbA}_{1c}\)\(> 7.0\) usually taken as a positive diagnosis of diabetes
Goal of analysis:
better understand effects of body size measurements on risk of DM
enhance screening for DM
Best way to develop a model for DM screening is not to fit binary logistic model with \(\text{HbA}_{1c}\) > 7 as the response variable
All cutpoints are arbitrary; no justification for any putative cut
\(\text{HbA}_{1c}\) 2=6.9, 7.1=10
Larger standard errors of \(\hat{\beta}\), lower power, wider confidence bands
Better: predict continuous \(\text{HbA}_{1c}\) using continuous response model, then convert to probability \(\text{HbA}_{1c}\) exceeds any cutoff or estimate 0.9 quantile of \(\text{HbA}_{1c}\)
15 Continous Variables of 18 Variables, 4629 Observations
Variable
Label
Units
n
Missing
Distinct
Info
Mean
pMedian
Gini |Δ|
Quantiles
.05 .10 .25 .50 .75 .90 .95
seqn
Respondent sequence number
4629
0
4629
1.000
56902
56902
3501
52136 52633 54284 56930 59495 61079 61641
age
Age
years
4629
0
703
1.000
48.57
48.29
19.85
23.33 26.08 33.92 46.83 61.83 74.83 80.00
wt
Weight
kg
4629
0
890
1.000
80.49
78.9
22.34
52.44 57.18 66.10 77.70 91.40 106.52 118.00
ht
Standing Height
cm
4629
0
512
1.000
167.5
167.4
11.71
151.1 154.4 160.1 167.2 175.0 181.0 184.8
bmi
Body Mass Index
kg/m2
4629
0
1994
1.000
28.59
28.02
6.965
20.02 21.35 24.12 27.60 31.88 36.75 40.68
leg
Upper Leg Length
cm
4474
155
216
1.000
38.39
38.4
4.301
32.0 33.5 36.0 38.4 41.0 43.3 44.6
arml
Upper Arm Length
cm
4502
127
156
1.000
37.01
37
3.116
32.6 33.5 35.0 37.0 39.0 40.6 41.7
armc
Arm Circumference
cm
4499
130
290
1.000
32.87
32.65
5.475
25.4 26.9 29.5 32.5 35.8 39.1 41.4
waist
Waist Circumference
cm
4465
164
716
1.000
97.62
96.9
17.18
74.8 78.6 86.9 96.3 107.0 117.8 125.0
tri
Triceps Skinfold
mm
4295
334
342
1.000
18.94
18.7
9.463
7.2 8.8 12.0 18.0 25.2 31.0 33.8
sub
Subscapular Skinfold
mm
3974
655
329
1.000
20.8
20.6
9.124
8.60 10.30 14.40 20.30 26.58 32.00 35.00
gh
Glycohemoglobin
%
4629
0
63
0.994
5.533
5.5
0.5411
4.8 5.0 5.2 5.5 5.8 6.0 6.3
albumin
Albumin
g/dL
4576
53
26
0.990
4.261
4.25
0.3528
3.7 3.9 4.1 4.3 4.5 4.7 4.8
bun
Blood urea nitrogen
mg/dL
4576
53
50
0.995
13.03
12.5
5.309
7 8 10 12 15 19 22
SCr
Creatinine
mg/dL
4576
53
167
1.000
0.8887
0.855
0.2697
0.58 0.62 0.72 0.84 0.99 1.14 1.25
w Descriptives
3 Categorical Variables of 18 Variables, 4629 Observations
Variable
Label
n
Missing
Distinct
sex
4629
0
2
re
Race/Ethnicity
4629
0
5
income
Family Income
4389
240
14
Code
dd <-datadist(w); options(datadist='dd')
15.2 The Linear Model
The most popular multivariable model for analyzing a univariate continuous \(Y\) is the the linear model \[
E(Y | X) = X \beta,
\] where \(\beta\) is estimated using ordinary least squares, that is, by solving for \(\hat{\beta}\) to minimize \(\sum (Y_{i} - X \hat{\beta})^{2}\).
To compute \(P\)-values and confidence limits using parametric methods (and for least squares estimates to coincide with maximum likelihood estimates) we would have to assume that \(Y | X\) is normal with mean \(X \beta\) and constant variance \(\sigma^2\)1
F
1 The latter assumption may be dispensed with if we use a robust Huber-White or bootstrap covariance matrix estimate. Normality may sometimes be dispensed with by using bootstrap confidence intervals, but this would not fix inefficiency problems with OLS when residuals are non-normal.
15.2.1 Checking Assumptions of OLS and Other Models
First see if gh would make a Gaussian residuals model fit
Use ordinary regression on 4 key variables to collapse into one variable (predicted mean from OLS model)
Stratify predicted mean into 6 quantile groups
Apply the normal inverse ECDF of gh to these strata and check for normality and constant \(\sigma^2\)
ECDF is for \(\Pr[Y \leq y | X]\) but for ordinal modeling we want to state models in terms of \(\Pr[Y \ge y | X]\) so take 1 - ECDF before inverse transforming
G
Code
f <-ols(gh ~rcs(age,5) + sex + re +rcs(bmi, 3), data=w)setDT(w) # make w a data.tablew[, pgh :=fitted(f)]w[, pgh6 :=cut2(pgh, g=6)]u <- w[, ecdfSteps(gh, extend=FALSE), by=pgh6] # ecdfSteps is in Hmiscv <-rbind(data.table(trans='paste(Phi^-1, (F[n](x)))', u[, z :=qnorm(1- y) ]),data.table(trans='logit(F[n](x))', u[, z :=qlogis(1- y) ]),data.table(trans='-log(-log(F[n](x)))', u[, z :=-log(-log(1- y))]),data.table(trans='log(-log(1-F[n](x)))', u[, z :=log(-log(y)) ]))v <- v[!is.infinite(z)]ggplot(v, aes(x, z, color=pgh6)) +geom_step() +facet_wrap(~ trans, label='label_parsed', scales='free_y') +xlab(expression(HbA[`1c`])) +theme(legend.position='bottom')# Get slopes of pgh for some cutoffs of Y# Use glm complementary log-log link on Prob(Y < cutoff) to# get log-log link on Prob(Y >= cutoff)r <-NULLfor(link inc('logit','probit','cloglog'))for(k inc(5, 5.5, 6)) { co <-coef(glm(gh < k ~ pgh, data=w, family=binomial(link))) r <-rbind(r, data.frame(link=link, cutoff=k,slope=round(co[2],2)))}print(r, row.names=FALSE)
No distributional assumptions other than continuity of \(Y\)
All the usual right hand side assumptions
When there is a single predictor that is categorical, quantile regression coincides with ordinary sample quantiles stratified by that predictor
Is transformation invariant - pre-transforming \(Y\) not important
I
Let \(\rho_{\tau}(y) = y(\tau - [y < 0])\). The \(\tau^{\mathrm th}\) sample quantile is the minimizer \(q\) of \(\sum_{i-1}^{n}\rho_{\tau}(y_{i}-q)\). For a conditional \(\tau^{\mathrm th}\) quantile of \(Y | X\) the corresponding quantile regression estimator \(\hat{\beta}_{\tau}\) minimizes \(\sum_{i=1}^{n}\rho_{\tau}(Y_{i}-X\beta)\). Quantile regression is not as efficient at estimating quantiles as is ordinary least squares at estimating the mean, if the latter’s assumptions hold. Koenker’s quantreg package in R(Roger Koenker, 2009) implements quantile regression, and the rms package’s Rq function provides a front-end that gives rise to various graphics and inference tools. If we model the median gh as a function of covariates, only the \(X\beta\) structure need be correct. Other quantiles (e.g., \(90^\text{th}\) percentile) can be directly modeled but standard errors will be much larger as it is more difficult to precisely estimate outer quantiles.
J
15.4 Ordinal Regression Models for Continuous \(Y\)
Advantages of semiparametric models (e.g., quantile regression and cumulative probability ordinal models
For ordinal cumulative probability models, there is no distributional assumption for \(Y\) given a setting of \(X\)
Assume only a connection between distributions of \(Y\) for different \(X\)
Applying an increasing 1–1 transformation to \(Y\) results in no change to regression coefficient estimates3
Regression coefficient estimates are completely robust to extreme \(Y\) values4
Estimates of quantiles of \(Y\) are exactly transformation-preserving, e.g., estimate of median of \(\log Y\) is exactly the log of the estimate of median \(Y\)
Manuguerra & Heller (2010) developed an ordinal model for continuous \(Y\) which they incorrectly labeled semi-parametric and is actually a lower-dimensional flexible parametric model that instead of having intercepts has a spline function of \(y\).
K
3 For symmetric distributions applying a decreasing transformation will negate the coefficients. For asymmetric distributions (e.g., Gumbel), reversing the order of \(Y\) will do more than change signs.
4 Only an estimate of mean \(Y\) from these \(\hat{\beta}\)s is non-robust.
For a general continuous distribution function \(F(y)\), an ordinal regression model based on cumulative probabilities may be stated as follows5. Let the ordered unique values of \(Y\) be denoted by \(y_{1}, y_{2}, \dots, y_{k}\) and let the intercepts associated with \(y_{1}, \dots, y_{k}\) be \(\alpha_{1}, \alpha_{2}, \dots, \alpha_{k}\), where \(\alpha_{1} =
\infty\) because \(\Pr[Y \geq y_{1}] = 1\). Let \(\alpha_{y} =
\alpha_{i}, i:y_{i}=y\). Then \[
\Pr[Y \geq y_{i} | X] = F(\alpha_{i} + X\beta) = F(\alpha_{y_{i}} + X\beta)
\] For the OLS fully parametric case, the model may be restated
L
5 It is more traditional to state the model in terms of \(\Pr[Y \leq y | X]\) but we use \(\Pr[Y \geq y | X]\) so that higher predicted values are associated with higher \(Y\).
so that to within an additive constant ^[\(\hat{\alpha_{y}}\) are unchanged if a constant is added to all \(y\).} \(\alpha_{y} = \frac{-y}{\sigma}\) (intercepts \(\alpha\) are linear in \(y\) whereas they are arbitrarily descending in the ordinal model), and \(\sigma\) is absorbed in \(\beta\) to put the OLS model into the new notation. The general ordinal regression model assumes that for fixed \(X_{1}, X_{2}\),
\[\begin{array}{c}
F^{-1}(\Pr[Y \geq y | X_{2}]) - F^{-1}(\Pr[Y \geq y | X_{1}])\\
= (X_{2} - X_{1})\beta
\end{array}\]
independent of the \(\alpha\)s (parallelism assumption). If \(F = [1 +
\exp(-y)]^{-1}\), this is the proportional odds assumption.
Common choices of \(F\), implemented in the rmsorm function, are shown in Table Table 15.1.
M
Table 15.1: Distribution families used in ordinal cumulative probability models. \(\Phi\) denotes the Gaussian cumulative distribution function. For the Connection column, \(P_{1}=\Pr[Y \geq y | X_{1}], P_{2}=\Pr[Y \geq y | X_{2}], \Delta=(X_{2}-X_{1})\beta\). The connection specifies the only distributional assumption if the model is fitted semiparametrically, i.e, contains an intercept for every unique \(Y\) value less one. For parametric models, \(P_{1}\) must be specified absolutely instead of just requiring a relationship between \(P_{1}\) and \(P_{2}\). For example, the traditional Gaussian parametric model specifies that \(\Pr[Y \geq y | X] = 1 - \Phi(\frac{y - X\beta}{\sigma}) = \Phi(\frac{-y + X\beta}{\sigma})\).
The Gumbel maximum value distribution is also called the extreme value type I distribution. This distribution (\(\log-\log\) link) also represents a continuous time proportional hazards model. The hazard ratio when \(X\) changes from \(X_{1}\) to \(X_{2}\) is \(\exp(-(X_{2} -
X_{1}) \beta)\). The mean of \(Y | X\) is easily estimated by computing \[
\sum_{i=1}^{k} y_{i} \hat{\Pr}[Y = y_{i} | X]
\] and the \(q^\text{th}\) quantile of \(Y | X\) is \(y\) such that \(F^{-1}(1 - q) - X\hat{\beta} = \hat{\alpha}_{y}\).6 The orm function in the rms package takes advantage of the information matrix being of a sparse tri-band diagonal form for the intercept parameters. This makes the computations efficient even for hundreds of intercepts (i.e., unique values of \(Y\)). orm is made to handle continuous \(Y\). Ordinal regression has nice properties in addition to those listed above, allowing for
N
6 The intercepts have to be shifted to the left one position in solving this equation because the quantile is such that \(\Pr[Y \leq y] = q\) whereas the model is stated in terms of \(\Pr[Y \geq y]\).
estimation of quantiles as efficiently as quantile regression if the parallel slopes assumptions hold
efficient estimation of mean \(Y\)
direct estimation of \(\Pr[Y\geq y | X]\)
arbitrary clumping of values of \(Y\), while still estimating \(\beta\) and mean \(Y\) efficiently7
solutions for \(\hat{\beta}\) using ordinary Newton-Raphson or other popular optimization techniques
being based on a standard likelihood function, penalized estimation can be straightforward
Wald, score, and likelihood ratio \(\chi^2\) tests that are more powerful than tests from quantile regression
O
7 But it is not sensible to estimate quantiles of \(Y\) when there are heavy ties in \(Y\) in the area containing the quantile.
To summarize how assumptions of parametric models compare to assumptions of semiparametric models, consider the ordinary linear model or its special case the equal variance two-sample \(t\)-test, vs. the probit or logit (proportional odds) ordinal model or their special cases the Van der Waerden (normal-scores) two-sample test or the Wilcoxon test. All the assumptions of the linear model other than independence of residuals are captured in the following (written in traditional \(Y\leq y\) form):
On the other hand, ordinal models assume the following: \[
\Pr[Y \leq y|X] = F(g(y)-X\beta),
\] where \(g\) is unknown and may be discontinuous. From this point we revert back to \(Y\geq y\) notation so that \(Y\) increases as \(X\beta\) increases.
Global Modeling Implications
Ordinal regression invariant to choice of transformation of \(Y\)
\(Y\) needs to be ordinal
Difference in two ordinal variables is not necessarily ordinal
\(\rightarrow\) Never analyze differences in regression
\(Y\)=final value, adjust for baseline values as covariates
Q
15.5 Ordinal Regression Applied to \(\text{HbA}_{1c}\)
In Figure 15.1, logit inverse curves are not parallel so proportional odds assumption does not hold
log-log link yields highest degree of parallelism and most constant regression coefficients across cutoffs of gh so use this link in an ordinal regression model (linearity of the curves is not required)
R
15.5.1 Checking Fit for Various Models Using Age
S
Another way to examine model fit is to flexibly fit the single most important predictor (age) using a variety of methods, and comparing predictions to sample quantiles and means based on overlapping subsets on age, each subset being subjects having age \(< 5\) years away from the point being predicted by the models. Here we predict the 0.5, 0.75, and 0.9 quantiles and the mean. For quantiles we can compare to quantile regression(discussed below) and for means we compare to OLS.
Code
require(data.table)require(ggplot2)estimands <-.q(q2, q3, p90, mean)links <-.q(logistic, probit, loglog, cloglog)estimators <-c(.q(empirical, ols, QR), links)ages <-25:75nage <-length(ages)yhat <-numeric(length(ages))fmt <-function(x) format(round(x, 3), nsmall=3)r <-expand.grid(estimand=estimands, estimator=estimators, age=ages, y=NA_real_, stringsAsFactors=FALSE)setDT(r)# Discard irrelevant methods for estimandsr <- r[! (estimand =='mean'& estimator =='QR') &! (estimand %in%.q(q2, q3, p90) & estimator =='ols'), ]# Find all used combinationsrc <- r[age ==25]rc[, age :=NULL]mod <- gh ~rcs(age,6)# Compute estimates for all relevant combinations of estimands & estimatorsfor(eor in rc[, unique(estimator)]) {if(eor =='empirical') { emp <-matrix(NA, nrow=nage, ncol=4,dimnames=list(NULL, .q(mean, q2, q3, p90)))for(j in1:length(ages)) { s <-which(abs(w$age - ages[j]) <5) y <- w$gh[s] a <-quantile(y, probs=c(0.5, 0.75, 0.90)) emp[j, ] <-c(mean(y), a) } }elseif(eor =='ols') fit <-ols(mod, data=w)elseif(eor %in% links) fit <-orm(mod, data=w, family=eor)for(eand in rc[estimator == eor, unique(estimand)]) { qa <-switch(eand, q2=0.5, q3=0.75, p90=0.90) yhat <-if(eor =='ols') Predict(fit, age=ages, conf.int=FALSE)$yhatelseif(eor =='empirical') emp[, eand] elseif(eor =='QR') { fit <-Rq(mod, data=w, tau=qa)Predict(fit, age=ages, conf.int=FALSE)$yhat }else { fun <-switch(eand,mean =Mean(fit),Quantile(fit)) fu <-if(eand =='mean') funelsefunction(x) fun(qa, x) Predict(fit, age=ages, fun=fu, conf.int=FALSE)$yhat } r[estimand == eand & estimator == eor, y := yhat] }}# Compute age-specific differences between estimates and empirical# estimates, then compute mean absolute differences across all agesdif <- r[estimator !='empirical']for(eor in rc[, setdiff(unique(estimator), 'empirical')]) for(eand in rc[estimator == eor, unique(estimand)]) dif[estimator == eor & estimand == eand]$y <- r[estimator == eor & estimand == eand]$y - r[estimator =='empirical'& estimand == eand]$ymad <- dif[, .(ad =mean(abs(y))), by=.(estimand, estimator)] mad2 <- mad[, .(value =paste(fmt(ad), collapse='\n'),label =paste(estimator, collapse='\n'),x =if(estimand =='p90') 60else25,y =if(estimand =='p90') 5.5else6.2), by=.(estimand)]ggplot() +geom_line(aes(x=age, y=y, col=estimator),data=r[estimator !='empirical']) +geom_point(aes(x=age, y=y, alpha=I(0.35)),data=r[estimator =='empirical']) +facet_wrap(~ estimand) +geom_text(aes(x=x, y=y, label=label, hjust='left', size=I(3)), data=mad2) +geom_text(aes(x=x+10, y=y, label=value, hjust='left', size=I(3)), data=mad2) +guides(color=guide_legend(title='')) +theme(legend.position='bottom')
T
It can be seen in Figure 15.3 that models dedicated to a specific task (quantile regression for quantiles and OLS for means) were best for those tasks. Although the log-log ordinal cumulative probability model did not estimate the median as accurately as some other methods, it does well for the 0.75 and 0.9 quantiles and is the best compromise overall because of its ability to also directly predict the mean as well as quantities such as \(\Pr[\text{HbA}_{1c} > 7 | X]\). For here on we focus on the log-log ordinal model. Going back to the bottom left of Figure 15.1, let’s look at quantile groups of predicted \(\text{HbA}_{1c}\) by OLS and plot predicted distributions of actual \(\text{HbA}_{1c}\) against empirical distributions.
U
Code
###w$pghg <- cut2(pgh, g=6)f <-orm(gh ~ pgh6, family=loglog, data=w)lp <-predict(f, newdata=data.frame(pgh6=levels(w$pgh6)))ep <-ExProb(f) # Exceedance prob. functn. generator in rmsz <-ep(lp)j <-order(w$pgh6) # puts in order of lp (levels of pghg)plot(z, xlim=c(4, 7.5), data=w[j,c('pgh6', 'gh')])
Agreement between predicted and observed exceedance probability distributions is excellent in Figure 15.4. To return to the initial look at a linear model with assumed Gaussian residuals, fit a probit ordinal model and compare the estimated intercepts to the linear relationship with gh that is assumed by the normal distribution.
The ratio of the coefficient of log height to the coefficient of log weight is -2.4, which is between what BMI uses and the more dimensionally reasonable weight / height\(^{3}\). By AIC, a spline interaction surface between height and weight does slightly better than BMI in predicting \(\text{HbA}_{1c}\), but a nonlinear function of BMI is barely worse. It will require other body size measures to displace BMI as a predictor. As an aside, compare this model fit to that from the Cox proportional hazards model. The Cox model uses a conditioning argument to obtain a partial likelihood free of the intercepts \(\alpha\) (and requires a second step to estimate these log discrete hazard components) whereas we are using a full marginal likelihood of the ranks of \(Y\)(Kalbfleisch & Prentice, 1973).
Back up and look at all body size measures, and examine their redundancies.
Y
Code
v <-varclus(~ wt + ht + bmi + leg + arml + armc + waist + tri + sub + age + sex + re, data=w)plot(v) # Omit wt so it won't be removed before bmir <-redun(~ ht + bmi + leg + arml + armc + waist + tri + sub,data=w, r2=.75)r
Redundancy Analysis
~ht + bmi + leg + arml + armc + waist + tri + sub
n: 3853 p: 8 nk: 3
Number of NAs: 0
Transformation of target variables forced to be linear
R-squared cutoff: 0.75 Type: ordinary
R^2 with which each variable can be predicted from all other variables:
ht bmi leg arml armc waist tri sub
0.829 0.924 0.682 0.748 0.843 0.864 0.531 0.594
Rendundant variables:
bmi ht
Predicted from variables:
leg arml armc waist tri sub
Variable Deleted R^2 R^2 after later deletions
1 bmi 0.924 0.909
2 ht 0.792
Code
r2describe(r$scores, nvmax=5) # show strongest predictors of each variable
Strongest Predictors of Each Variable With Cumulative R^2
ht
arml (0.658) + leg (0.765) + tri (0.786) + waist (0.788) + bmi (0.807)
bmi
waist (0.775) + armc (0.839) + ht (0.913) + tri (0.916) + leg (0.916)
leg
ht (0.632) + waist (0.646) + arml (0.663) + bmi (0.676) + tri (0.679)
arml
ht (0.658) + waist (0.721) + leg (0.735) + armc (0.738) + tri (0.742)
armc
bmi (0.716) + ht (0.814) + waist (0.821) + arml (0.824) + sub (0.828)
waist
bmi (0.775) + ht (0.828) + leg (0.84) + arml (0.845) + armc (0.851)
tri
sub (0.399) + ht (0.487) + bmi (0.518) + waist (0.522) + arml (0.524)
sub
bmi (0.464) + tri (0.558) + waist (0.568) + armc (0.573) + ht (0.573)
Six size measures adequately capture the entire set. Height and BMI are removed. An advantage of removing height is that it is age-dependent in the elderly:
Z
Code
f <-orm(ht ~rcs(age,4)*sex, data=w) # Prop. odds modelqu <-Quantile(f); med <-function(x) qu(.5, x)ggplot(Predict(f, age, sex, fun=med, conf.int=FALSE),ylab='Predicted Median Height, cm')
But also see a change in leg length:
Code
f <-orm(leg ~rcs(age,4)*sex, data=w)qu <-Quantile(f); med <-function(x) qu(.5, x)ggplot(Predict(f, age, sex, fun=med, conf.int=FALSE),ylab='Predicted Median Upper Leg Length, cm')
Next allocate d.f. according to generalized Spearman \(\rho^{2}\)8.
A
8 Competition between collinear size measures hurts interpretation of partial tests of association in a saturated additive model.
Code
spar(top=1, ps=9)s <-spearman2(gh ~ age + sex + re + wt + leg + arml + armc + waist + tri + sub, data=w, p=2)plot(s)
Parameters will be allocated in descending order of \(\rho^2\). But note that subscapular skinfold has a large number of NAs and other predictors also have NAs. Suboptimal casewise deletion will be used until the final model is fitted. Because there are many competing body measures, we use backwards stepdown to arrive at a set of predictors. The bootstrap will be used to penalize predictive ability for variable selection. First the full model is fit using casewise deletion, then we do a composite test to assess whether any of the frequently-missing predictors is important. Use likelihood ratio \(\chi^2\) tests.
B
Code
f <-orm(gh ~rcs(age,5) + sex + re +rcs(wt,3) +rcs(leg,3) + arml +rcs(armc,3) +rcs(waist,4) + tri +rcs(sub,3),family=loglog, data=w, x=TRUE, y=TRUE)print(f, coefs=FALSE)
-log-log Ordinal Regression Model
orm(formula = gh ~ rcs(age, 5) + sex + re + rcs(wt, 3) + rcs(leg,
3) + arml + rcs(armc, 3) + rcs(waist, 4) + tri + rcs(sub,
3), data = w, x = TRUE, y = TRUE, family = loglog)
The model yields Spearman \(\rho=0.52\), the rank correlation between predicted and observed \(\text{HbA}_{1c}\). Show predicted mean and median \(\text{HbA}_{1c}\) as a function of age, adjusting other variables to median/mode. Compare the estimate of the median with that from quantile regression (discussed below).
Next do fast backward step-down in an attempt to get a model without so much competition among variables. The stepwise selection will be penalized for in the model validation.
D
Code
print(fastbw(f, rule='p'), estimates=FALSE)
Deleted Chi-Sq d.f. P Residual d.f. P AIC
arml 0.16 1 0.6924 0.16 1 0.6924 -1.84
sex 0.45 1 0.5019 0.61 2 0.7381 -3.39
wt 5.72 2 0.0572 6.33 4 0.1759 -1.67
armc 3.32 2 0.1897 9.65 6 0.1400 -2.35
Factors in Final Model
[1] age re leg waist tri sub
Validate the model, properly penalizing for variable selection
E
Code
g <-function() {set.seed(13) # so can reproduce resultsvalidate(f, B=100, bw=TRUE, estimates=FALSE, rule='p')}v <-runifChanged(g)
Code
# Show number of variables selected in first 30 bootsprint(v, B=30)
Index
Original
Sample
Training
Sample
Test
Sample
Optimism
Corrected
Index
Successful
Resamples
ρ
0.5225
0.5279
0.5204
0.0076
0.5149
100
R2
0.2712
0.2778
0.2689
0.0089
0.2623
100
Slope
1
1
0.979
0.021
0.979
100
g
1.2276
1.2483
1.2196
0.0287
1.1989
100
Mean |Pr(Y≥Y0.5)-0.5|
0.2007
0.2058
0.1988
0.007
0.1937
100
Factors Retained in Backwards Elimination
First 30 Resamples
age
sex
re
wt
leg
arml
armc
waist
tri
sub
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Frequencies of Numbers of Factors Retained
5
6
7
8
9
2
20
30
45
3
Develop multiple imputations then repeat the bootstrap validation process, but separately for each completed dataset. The overall validation averages the bootstrap-corrected model performance measures over five validations.
Code
set.seed(11)a <-aregImpute(~ gh + age + sex + re + wt + leg + arml + armc + waist + tri + sub, data=w, n.impute=5, pr=FALSE)a
Multiple Imputation using Bootstrap and PMM
aregImpute(formula = ~gh + age + sex + re + wt + leg + arml +
armc + waist + tri + sub, data = w, n.impute = 5, pr = FALSE)
n: 4629 p: 11 Imputations: 5 nk: 3
Number of NAs:
gh age sex re wt leg arml armc waist tri sub
0 0 0 0 0 155 127 130 164 334 655
type d.f.
gh s 2
age s 2
sex c 1
re c 4
wt s 2
leg s 2
arml s 2
armc s 2
waist s 2
tri s 2
sub s 1
Transformation of Target Variables Forced to be Linear
R-squares for Predicting Non-Missing Values for Each Variable
Using Last Imputations of Predictors
leg arml armc waist tri sub
0.638 0.720 0.862 0.904 0.746 0.641
Code
v <-function(fit)list(validate=validate(fit, B=100, bw=TRUE, estimates=FALSE, prmodsel=FALSE, rule='p', pr=FALSE))h <-function()fit.mult.impute(gh ~rcs(age,5) + sex + re +rcs(wt,3) +rcs(leg,3) + arml +rcs(armc,3) +rcs(waist,4) + tri +rcs(sub,3), orm, a, data=w,fun=v, fitargs=list(x=TRUE, y=TRUE, family='loglog'), pr=FALSE)f <-runifChanged(h, a, v) # 11mprint(processMI(f, 'validate'), B=10, digits=3)
Index
Original
Sample
Training
Sample
Test
Sample
Optimism
Corrected
Index
Successful
Resamples
ρ
0.517
0.522
0.516
0.005
0.512
500
R2
0.27
0.276
0.269
0.007
0.264
500
Slope
1
1
0.983
0.017
0.983
500
g
1.227
1.244
1.223
0.021
1.206
500
Mean |Pr(Y≥Y0.5)-0.5|
0.2
0.201
0.198
0.003
0.197
500
Factors Retained in Backwards Elimination
First 10 Resamples
age
sex
re
wt
leg
arml
armc
waist
tri
sub
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Frequencies of Numbers of Factors Retained
6
7
8
9
10
30
54
6
There is no calibrate method for orm model fits.
Next fit the reduced model. Use multiple imputation to impute missing predictors. Do a LR ANOVA for the reduced model, taking imputation into account.
FG
Code
h <-function()fit.mult.impute(gh ~rcs(age,5) + re +rcs(leg,3) +rcs(waist,4) + tri +rcs(sub,4), orm, a, fitargs=list(family='loglog'),lrt=TRUE,data=w, pr=FALSE)g <-runifChanged(h, a)g
-log-log Ordinal Regression Model
fit.mult.impute(formula = gh ~ rcs(age, 5) + re + rcs(leg, 3) +
rcs(waist, 4) + tri + rcs(sub, 4), fitter = orm, xtrans = a,
data = w, lrt = TRUE, pr = FALSE, fitargs = list(family = "loglog"))
Model Likelihood
Ratio Test
Discrimination
Indexes
Rank Discrim.
Indexes
Obs 4629
LR χ2 1443.45
R2 0.269
ρ 0.512
Distinct Y 63
d.f. 17
R217,23145 0.267
Y0.5 5.5
Pr(>χ2) <0.0001
R217,23011.2 0.269
max |∂log L/∂β| 6×10-5
Score χ2 7820.99
|Pr(Y ≥ median)-½| 0.173
Pr(>χ2) <0.0001
β
S.E.
Wald Z
Pr(>|Z|)
age
0.0405
0.0055
7.35
<0.0001
age'
-0.0226
0.0277
-0.82
0.4146
age''
0.0114
0.0871
0.13
0.8958
age'''
0.0448
0.1145
0.39
0.6958
re=Other Hispanic
-0.0703
0.0592
-1.19
0.2345
re=Non-Hispanic White
-0.4128
0.0450
-9.18
<0.0001
re=Non-Hispanic Black
0.0635
0.0562
1.13
0.2589
re=Other Race Including Multi-Racial
-0.0434
0.0746
-0.58
0.5607
leg
-0.0324
0.0092
-3.51
0.0004
leg'
0.0138
0.0107
1.28
0.1988
waist
0.0076
0.0050
1.52
0.1283
waist'
0.0305
0.0161
1.90
0.0576
waist''
-0.0916
0.0522
-1.76
0.0790
tri
-0.0159
0.0026
-6.04
<0.0001
sub
-0.0026
0.0097
-0.27
0.7881
sub'
0.0635
0.0307
2.07
0.0386
sub''
-0.1694
0.0999
-1.70
0.0898
Code
an <-processMI(g, 'anova')# Show penalty-type parameters for imputationprmiInfo(an)
Imputation penalties
Test
Missing
Information
Fraction
Denominator
d.f.
χ2 Discount
age
0.095
1760.5
0.905
Nonlinear
0.033
11155.4
0.967
re
0.000
Inf
1.000
leg
0.003
914800.9
0.997
Nonlinear
0.071
788.9
0.929
waist
0.000
Inf
1.000
Nonlinear
0.030
8609.4
0.970
tri
0.155
166.0
0.845
sub
0.301
132.9
0.699
Nonlinear
0.286
98.0
0.714
TOTAL NONLINEAR
0.100
3197.8
0.900
TOTAL
0.074
12487.9
0.926
Code
# Correct likelihood-based statistics for imputationg <-LRupdate(g, an)print(an, caption='ANOVA for reduced model after multiple imputation, with addition of a combined effect for four size variables')
ANOVA for reduced model after multiple imputation, with addition of a combined effect for four size variables
χ2
d.f.
P
age
630.21
4
<0.0001
Nonlinear
28.12
3
<0.0001
re
172.14
4
<0.0001
leg
24.25
2
<0.0001
Nonlinear
1.64
1
0.2009
waist
152.89
3
<0.0001
Nonlinear
3.87
2
0.1442
tri
33.22
1
<0.0001
sub
36.85
3
<0.0001
Nonlinear
5.28
2
0.0714
TOTAL NONLINEAR
42.48
8
<0.0001
TOTAL
1336.94
17
<0.0001
Code
b <-anova(g, leg, waist, tri, sub)# Add new lines to the plot with combined effect of 4 size var.s <-rbind(an, size=b['TOTAL', ])class(s) <-'anova.rms'
Code
spar(top=1)plot(s)
H
Code
ggplot(Predict(g), abbrev=TRUE, ylab=NULL)
I
Code
M <-Mean(g)ggplot(Predict(g, fun=M), abbrev=TRUE, ylab=NULL)
Compare the estimated age partial effects and confidence intervals with those from a model using casewise deletion, and with bootstrap nonparametric confidence intervals (also with casewise deletion).
J
Code
h <-function() { gc <-orm(gh ~rcs(age,5) + re +rcs(leg,3) +rcs(waist,4) + tri +rcs(sub,4),family=loglog, data=w, x=TRUE, y=TRUE) gb <-bootcov(gc, B=300)list(gc=gc, gb=gb)}gbc <-runifChanged(h)gc <- gbc$gcgb <- gbc$gb
```{r include=FALSE}require(Hmisc)options(qproject='rms', prType='html')require(qreport)getRs('qbookfun.r')hookaddcap()knitr::set_alias(w = 'fig.width', h = 'fig.height', cap = 'fig.cap', scap ='fig.scap')````r hba <- '$\\text{HbA}_{1c}$'`# Regression Models for Continuous $Y$ and Case Study in Ordinal Regression {#sec-cony}`r mrg(sound("ord-cont-1"))`This chapter concerns univariate continuous $Y$. There are manymultivariable models for predicting such response variables.`r ipacue()`* linear models with assumed normal residuals, fitted with ordinary least squares* generalized linear models and other parametric models based on special distributions such as the gamma* generalized additive models (GAMs)* generalization of GAMs to also nonparametrically transform $Y$* quantile regression (see Section @sec-cony-quantile-regression)* other robust regression models that, like quantile regression, use an objective different from minimizing the sum of squared errors [@VR]* semiparametric models based on the ranks of $Y$, such as the Cox proportional hazards model and the proportional odds ordinal logistic model* cumulative probability models (often called _cumulative link models_) which are semiparametric models from a wider class of families than the logisticSemiparametric models that treat $Y$ as ordinal but not `r ipacue()`interval-scaled have many advantages including robustness and freedomof distributional assumptions for $Y$ conditional on any given set ofpredictors.<!-- Semiparametric models assume only a connection between---><!-- the distribution of $Y | X_{1}$ and $Y | X_{2}$.--->Advantages are demonstrated in a case study of a cumulativeprobability ordinal model. Some of the results are compared to quantileregression and OLS. Many of the methods used in the case study also apply toordinary linear models.## Dataset and Descriptive Statistics`r mrg(sound("ord-cont-2"))`* Diabetes Mellitus (DM) type II (adult onset diabetes) is strongly `r ipacue()` associated with obesity* Primary laboratory test for diabetes: glycosylated hemoglobin (`r hba`), also called glycated hemoglobin, glycohemoglobin, or hemoglobin $A_{1c}$.* `r hba` reflects average blood glucose for the preceding 60 to 90 days* `r hba` $> 7.0$ usually taken as a positive diagnosis of diabetes* Goal of analysis: + better understand effects of body size measurements on risk of DM + enhance screening for DM* Best way to develop a model for DM screening is **not** to `r ipacue()` fit binary logistic model with `r hba` > 7 as the response variable + All cutpoints are arbitrary; no justification for any putative cut + `r hba` 2=6.9, 7.1=10 + Larger standard errors of $\hat{\beta}$, lower power, wider confidence bands + Better: predict continuous `r hba` using continuous response model, then convert to probability `r hba` exceeds any cutoff or estimate 0.9 quantile of `r hba`* Data: U.S. National Health and Nutrition Examination Survey (NHANES) `r ipacue()` from National Center for Health Statistics/CDC:[www.cdc.gov/nchs/nhanes.htm](http://www.cdc.gov/nchs/nhanes.htm)[@nhanes2010]* age $\geq 80$ coded as 80 by CDC* Subset with age $\geq 21$, neither diagnosed nor treated for DM* Transform `bmi`, just for the spike histograms```{r desc,results='asis'}require(rms)options(prType='html') # for print, summary, anova, describegetHdata(nhgh)w <- subset(nhgh, age >= 21 & dx==0 & tx==0, select=-c(dx,tx))des <- describe(w, trans=list(bmi= list('log', log, exp)))sparkline::sparkline(0) # loads jQuery javascript for sparklinesmaketabs(print(des, 'both'), wide=TRUE, initblank=TRUE)dd <- datadist(w); options(datadist='dd')```## The Linear Model {#sec-cony-linear-model}`r mrg(sound("ord-cont-3"))`The most popular multivariable model for analyzing a univariatecontinuous $Y$ is the the linear model$$E(Y | X) = X \beta,$$where $\beta$ is estimated using ordinary least squares, that is, bysolving for $\hat{\beta}$ to minimize $\sum (Y_{i} - X \hat{\beta})^{2}$.* To compute $P$-values and confidence limits using parametric `r ipacue()` methods (and for least squares estimates to coincide with maximum likelihood estimates) we would have to assume that $Y | X$ is normal with mean $X \beta$ and constant variance $\sigma^2$ ^[The latter assumption may be dispensed with if we use a robust Huber-White or bootstrap covariance matrix estimate. Normality may sometimes be dispensed with by using bootstrap confidence intervals, but this would not fix inefficiency problems with OLS when residuals are non-normal.]<!-- * Don't assume linearity; expand $X$s into rcs with no. knots---><!-- figured by predictive potential; use default knit locations---><!-- (selected quantiles of continuous predictors' marginal distributions)--->### Checking Assumptions of OLS and Other Models* First see if `gh` would make a Gaussian residuals model fit `r ipacue()`* Use ordinary regression on 4 key variables to collapse into one variable (predicted mean from OLS model)* Stratify predicted mean into 6 quantile groups* Apply the normal inverse ECDF of `gh` to these strata and check for normality and constant $\sigma^2$* ECDF is for $\Pr[Y \leq y | X]$ but for ordinal modeling we want to state models in terms of $\Pr[Y \ge y | X]$ so take 1 - ECDF before inverse transforming```{r lookdist,w=6.5,h=5.5,cap='Examination of normality and constant variance assumption, and assumptions for various ordinal models',scap='Examining normality and ordinal model assumptions'}#| label: fig-cony-lookdistf <- ols(gh ~ rcs(age,5) + sex + re + rcs(bmi, 3), data=w)setDT(w) # make w a data.tablew[, pgh := fitted(f)]w[, pgh6 := cut2(pgh, g=6)]u <- w[, ecdfSteps(gh, extend=FALSE), by=pgh6] # ecdfSteps is in Hmiscv <- rbind(data.table(trans='paste(Phi^-1, (F[n](x)))', u[, z := qnorm(1 - y) ]), data.table(trans='logit(F[n](x))', u[, z := qlogis(1 - y) ]), data.table(trans='-log(-log(F[n](x)))', u[, z := -log(-log(1 - y))]), data.table(trans='log(-log(1-F[n](x)))', u[, z := log(-log(y)) ]))v <- v[! is.infinite(z)]ggplot(v, aes(x, z, color=pgh6)) + geom_step() + facet_wrap(~ trans, label='label_parsed', scales='free_y') + xlab(expression(HbA[`1c`])) + theme(legend.position='bottom')# Get slopes of pgh for some cutoffs of Y# Use glm complementary log-log link on Prob(Y < cutoff) to# get log-log link on Prob(Y >= cutoff)r <- NULLfor(link in c('logit','probit','cloglog')) for(k in c(5, 5.5, 6)) { co <- coef(glm(gh < k ~ pgh, data=w, family=binomial(link))) r <- rbind(r, data.frame(link=link, cutoff=k, slope=round(co[2],2)))}print(r, row.names=FALSE)```* Lower right curves are not linear, implying that a normal `r ipacue()` conditional distribution cannot work for `gh`^[They are not parallel either.]* There is non-parallelism for the logit model* Other graphs will be used to guide selection of an ordinal model below## Quantile Regression {#sec-cony-quantile-regression}`r mrg(sound("ord-cont-4"))`* Ruled out OLS and semiparametric proportional odds model `r ipacue()`* Quantile regression [@koeqr; @koe78reg] is a different approach to modeling $Y$* No distributional assumptions other than continuity of $Y$* All the usual right hand side assumptions* When there is a single predictor that is categorical, quantile regression coincides with ordinary sample quantiles stratified by that predictor* Is transformation invariant - pre-transforming $Y$ not importantLet $\rho_{\tau}(y) = y(\tau - [y < 0])$. The $\tau^{\mathrm th}$sample `r ipacue()`quantile is the minimizer $q$ of$\sum_{i-1}^{n}\rho_{\tau}(y_{i}-q)$. For a conditional$\tau^{\mathrm th}$ quantile of $Y | X$ the corresponding quantile regression estimator$\hat{\beta}_{\tau}$ minimizes $\sum_{i=1}^{n}\rho_{\tau}(Y_{i}-X\beta)$.Quantile regression is not as efficient atestimating quantiles as is ordinary least squares at estimating themean, if the latter's assumptions hold.Koenker's `quantreg` package in `R`[@quantreg] implementsquantile regression, and the `rms` package's `Rq` functionprovides a front-end that gives rise to various graphics and inference tools.If we model the median `gh` as a function of covariates, only the$X\beta$ structure need be correct. Other quantiles (e.g.,$90^\text{th}$ percentile) can be directly modeled but standard errors willbe much larger as it is more difficult to precisely estimate outer quantiles.## Ordinal Regression Models for Continuous $Y$`r mrg(sound("ord-cont-5"))`* Advantages of semiparametric models (e.g., quantile regression `r ipacue()` and cumulative probability ordinal models* For ordinal cumulative probability models, there is no distributional assumption for $Y$ given a setting of $X$* Assume only a connection between distributions of $Y$ for different $X$* Applying an increasing 1--1 transformation to $Y$ results in no change to regression coefficient estimates^[For symmetric distributions applying a decreasing transformation will negate the coefficients. For asymmetric distributions (e.g., Gumbel), reversing the order of $Y$ will do more than change signs.]* Regression coefficient estimates are completely robust to extreme $Y$ values^[Only an estimate of mean $Y$ from these $\hat{\beta}$s is non-robust.]* Estimates of quantiles of $Y$ are exactly transformation-preserving, e.g., estimate of median of $\log Y$ is exactly the log of the estimate of median $Y$* @man10ord developed an ordinal model for continuous $Y$ which they incorrectly labeled semi-parametric and is actually a lower-dimensional flexible parametric model that instead of having intercepts has a spline function of $y$.----For a general continuous distribution `r ipacue()` function $F(y)$, an ordinalregression model based on cumulative probabilities may be stated asfollows^[It is more traditional to state the model in terms of $\Pr[Y \leq y | X]$ but we use $\Pr[Y \geq y | X]$ so that higher predicted values are associated with higher $Y$.]. Let the orderedunique values of $Y$ be denoted by $y_{1}, y_{2}, \dots, y_{k}$ andlet the intercepts associated with $y_{1}, \dots, y_{k}$ be$\alpha_{1}, \alpha_{2}, \dots, \alpha_{k}$, where $\alpha_{1} =\infty$ because $\Pr[Y \geq y_{1}] = 1$. Let $\alpha_{y} =\alpha_{i}, i:y_{i}=y$. Then$$\Pr[Y \geq y_{i} | X] = F(\alpha_{i} + X\beta) = F(\alpha_{y_{i}} + X\beta)$$For the OLS fully parametric case, the model maybe restated\begin{array}{c}\Pr[Y \geq y | X] = \Pr[\frac{Y-X\beta}{\sigma} \geq \frac{y-X\beta}{\sigma}]\\ = 1-\Phi(\frac{y-X\beta}{\sigma}) = \Phi(\frac{-y}{\sigma}+\frac{X\beta}{\sigma})\end{array}so that to within an additive constant ^[$\hat{\alpha_{y}}$ are unchanged if a constant is added to all $y$.} $\alpha_{y} = \frac{-y}{\sigma}$ (intercepts $\alpha$ arelinear in $y$ whereas they are arbitrarily descending in the ordinal model), and$\sigma$ is absorbed in $\beta$ to put the OLS model into the new notation.The general ordinal regression model assumes that for fixed $X_{1}, X_{2}$,\begin{array}{c}F^{-1}(\Pr[Y \geq y | X_{2}]) - F^{-1}(\Pr[Y \geq y | X_{1}])\\= (X_{2} - X_{1})\beta\end{array}independent of the $\alpha$s (parallelism assumption). If $F = [1 + \exp(-y)]^{-1}$, this is the proportional odds assumption.Common choices of $F$, implemented in the `rms``orm` function,are shown in Table @tbl-cony-ormdist. `r ipacue()`| Distribution | $F$ | Inverse (Link Function) | Link Name | Connection ||-----|-----|-----|-----|-----|| Logistic | $[1 + \exp(-y)]^{-1}$ | $\log(\frac{y}{1-y})$ | logit | $\frac{P_{2}}{1-P_{2}} = \frac{P_{1}}{1-P_{1}} \exp(\Delta)$ || Gaussian | $\Phi(y)$ | $\Phi^{-1}(y)$ | probit | $P_{2}=\Phi(\Phi^{-1}(P_{1})+\Delta)$ || Gumbel maximum value| $\exp(-\exp(-y))$ | $\log(-\log(y))$ | $\log-\log$ | $P_{2}=P_{1}^{\exp(\Delta)}$ || Gumbel minimum value| $1 - \exp(-\exp(y))$ | $\log(-\log(1 - y))$ | complementary $\log-\log$ | $1-P_{2}=(1-P_{1})^{\exp(\Delta)}$ || Cauchy | $\frac{1}{\pi}\tan^{-1}(y) + \frac{1}{2}$ | $\tan[\pi(y - \frac{1}{2})]$ | cauchit |: Distribution families used in ordinal cumulative probability models. $\Phi$ denotes the Gaussian cumulative distribution function. For the Connection column, $P_{1}=\Pr[Y \geq y | X_{1}], P_{2}=\Pr[Y \geq y | X_{2}], \Delta=(X_{2}-X_{1})\beta$. The connection specifies the only distributional assumption if the model is fitted semiparametrically, i.e, contains an intercept for every unique $Y$ value less one. For parametric models, $P_{1}$ must be specified absolutely instead of just requiring a relationship between $P_{1}$ and $P_{2}$. For example, the traditional Gaussian parametric model specifies that $\Pr[Y \geq y | X] = 1 - \Phi(\frac{y - X\beta}{\sigma}) = \Phi(\frac{-y + X\beta}{\sigma})$. {#tbl-cony-ormdist}The Gumbel maximum value distribution is also called the extreme valuetype I distribution. This distribution($\log-\log$ link) also represents a continuous time proportionalhazards model. The hazardratio when $X$ changes from $X_{1}$ to $X_{2}$ is $\exp(-(X_{2} -X_{1}) \beta)$.The mean of $Y | X$ is easily estimated by computing `r ipacue()`$$\sum_{i=1}^{k} y_{i} \hat{\Pr}[Y = y_{i} | X]$$and the $q^\text{th}$ quantile of $Y | X$ is $y$ such that <br>$F^{-1}(1 - q) - X\hat{\beta} = \hat{\alpha}_{y}$.^[The intercepts have to be shifted to the left one position in solving this equation because the quantile is such that $\Pr[Y \leq y] = q$ whereas the model is stated in terms of $\Pr[Y \geq y]$.]The `orm` function in the `rms` package takes advantage of theinformation matrix being of a sparse tri-band diagonal form for theintercept parameters. This makes the computations efficient even forhundreds of intercepts (i.e., unique values of $Y$). `orm` is madeto handle continuous $Y$.Ordinal regression has nice properties in addition to those listedabove, allowing for* estimation of quantiles as efficiently as quantile `r ipacue()` regression if the parallel slopes assumptions hold* efficient estimation of mean $Y$* direct estimation of $\Pr[Y\geq y | X]$* arbitrary clumping of values of $Y$, while still estimating $\beta$ and mean $Y$ efficiently^[But it is not sensible to estimate quantiles of $Y$ when there are heavy ties in $Y$ in the area containing the quantile.]* solutions for $\hat{\beta}$ using ordinary Newton-Raphson or other popular optimization techniques* being based on a standard likelihood function, penalized estimation can be straightforward* Wald, score, and likelihood ratio $\chi^2$ tests that are more powerful than tests from quantile regressionTo summarize how assumptions of parametric models `r ipacue()` compare toassumptions of semiparametric models, consider the ordinary linearmodel or its special case the equal variancetwo-sample $t$-test, vs. the probit or logit (proportional odds)ordinal model or their special cases the Van der Waerden(normal-scores) two-sample test or the Wilcoxon test. All theassumptions of the linear model other than independence of residualsare captured in the following (written in traditional $Y\leq y$ form):\begin{array}{c}F(y|X) = \Pr[Y \leq y|X] = \Phi(\frac{y-X\beta}{\sigma})\\\Phi^{-1}(F(y|X)) = \frac{y-X\beta}{\sigma}\end{array}```{r lmassump,h=3.5,w=8,left=2,cap='Assumptions of the linear model (left panel) and semiparametric ordinal probit or logit (proportional odds) models (right panel). Ordinal models do not assume any shape for the distribution of $Y$ for a given $X$; they only assume parallelism.',scap='Assumptions of linear vs. semiparametric models'}#| label: fig-cony-lmassumpspar(mfrow=c(1,2), left=2)pinv <- expression(paste(Phi^{-1}, '(F(y', '|', 'X))'))plot(0, 0, xlim=c(0, 1), ylim=c(-2, 2), type='n', axes=FALSE, xlab=expression(y), ylab='')mtext(pinv, side=2, line=1)axis(1, labels=FALSE, lwd.ticks=0)axis(2, labels=FALSE, lwd.ticks=0)abline(a=-1.5, b=1)abline(a=0, b=1)arrows(.5, -1.5+.5, .5, 0+.5, code=3, length=.1)text(.525, .5*(-1.5+.5+.5), expression(-Delta*X*beta/sigma), adj=0)g <- function(x) -2.2606955+11.125231*x-37.772783*x^2+56.776436*x^3- 26.861103*x^4x <- seq(0, .9, length=150)pinv <- expression(atop(paste(Phi^{-1}, '(F(y', '|', 'X))'), paste(logit, '(F(y', '|', 'X))')))plot(0, 0, xlim=c(0, 1), ylim=c(-2, 2), type='n', axes=FALSE, xlab=expression(y), ylab='')mtext(pinv, side=2, line=1)axis(1, labels=FALSE, lwd.ticks=FALSE)axis(2, labels=FALSE, lwd.ticks=FALSE)lines(x, g(x))lines(x, g(x)+1.5)arrows(.5, g(.5), .5, g(.5)+1.5, code=3, length=.1)text(.525, .5*(g(.55) + g(.55)+1.5), expression(-Delta*X*beta), adj=0)```On the other hand, ordinal models assume the following:$$\Pr[Y \leq y|X] = F(g(y)-X\beta),$$where $g$ is unknown and may be discontinuous.From this point we revert back to $Y\geq y$ notation so that $Y$increases as $X\beta$ increases.**Global Modeling Implications*** Ordinal regression invariant to choice of transformation of $Y$ `r ipacue()`* $Y$ needs to be ordinal* Difference in two ordinal variables is not necessarily ordinal* $\rightarrow$ Never analyze differences in regression* $Y$=final value, adjust for baseline values as covariates## Ordinal Regression Applied to `r hba``r mrg(sound("ord-cont-6"))`* In @fig-cony-lookdist, logit inverse curves are not `r ipacue()` parallel so proportional odds assumption does not hold* log-log link yields highest degree of parallelism and most constant regression coefficients across cutoffs of `gh` so use this link in an ordinal regression model (linearity of the curves is not required)### Checking Fit for Various Models Using Age`r ipacue()`Another way to examine model fit is to flexibly fit the single mostimportant predictor (age) using a variety of methods, and comparingpredictions to sample quantiles and means based on overlapping subsetson age, each subset being subjects having age $< 5$ years away fromthe point being predicted by the models. Here we predict the 0.5,0.75, and 0.9 quantiles and the mean. For quantiles we can compare toquantile regression(discussed below) and for means we compare to OLS.```{r comparemany,h=6.5,w=6.75,cap='Three estimated quantiles and estimated mean using 6 methods, compared against caliper-matched sample quantiles/means (circles). Numbers are mean absolute differences between predicted and sample quantities using overlapping intervals of age and caliper matching. QR:quantile regression.',scap='Six methods for estimating quantiles or means.'}#| label: fig-cony-comparemanyrequire(data.table)require(ggplot2)estimands <- .q(q2, q3, p90, mean)links <- .q(logistic, probit, loglog, cloglog)estimators <- c(.q(empirical, ols, QR), links)ages <- 25 : 75nage <- length(ages)yhat <- numeric(length(ages))fmt <- function(x) format(round(x, 3), nsmall=3)r <- expand.grid(estimand=estimands, estimator=estimators, age=ages, y=NA_real_, stringsAsFactors=FALSE)setDT(r)# Discard irrelevant methods for estimandsr <- r[! (estimand == 'mean' & estimator == 'QR') & ! (estimand %in% .q(q2, q3, p90) & estimator == 'ols'), ]# Find all used combinationsrc <- r[age == 25]rc[, age := NULL]mod <- gh ~ rcs(age,6)# Compute estimates for all relevant combinations of estimands & estimatorsfor(eor in rc[, unique(estimator)]) { if(eor == 'empirical') { emp <- matrix(NA, nrow=nage, ncol=4, dimnames=list(NULL, .q(mean, q2, q3, p90))) for(j in 1 : length(ages)) { s <- which(abs(w$age - ages[j]) < 5) y <- w$gh[s] a <- quantile(y, probs=c(0.5, 0.75, 0.90)) emp[j, ] <- c(mean(y), a) } } else if(eor == 'ols') fit <- ols(mod, data=w) else if(eor %in% links) fit <- orm(mod, data=w, family=eor) for(eand in rc[estimator == eor, unique(estimand)]) { qa <- switch(eand, q2=0.5, q3=0.75, p90=0.90) yhat <- if(eor == 'ols') Predict(fit, age=ages, conf.int=FALSE)$yhat else if(eor == 'empirical') emp[, eand] else if(eor == 'QR') { fit <- Rq(mod, data=w, tau=qa) Predict(fit, age=ages, conf.int=FALSE)$yhat } else { fun <- switch(eand, mean = Mean(fit), Quantile(fit)) fu <- if(eand == 'mean') fun else function(x) fun(qa, x) Predict(fit, age=ages, fun=fu, conf.int=FALSE)$yhat } r[estimand == eand & estimator == eor, y := yhat] }}# Compute age-specific differences between estimates and empirical# estimates, then compute mean absolute differences across all agesdif <- r[estimator != 'empirical']for(eor in rc[, setdiff(unique(estimator), 'empirical')]) for(eand in rc[estimator == eor, unique(estimand)]) dif[estimator == eor & estimand == eand]$y <- r[estimator == eor & estimand == eand]$y - r[estimator == 'empirical' & estimand == eand]$ymad <- dif[, .(ad = mean(abs(y))), by=.(estimand, estimator)] mad2 <- mad[, .(value = paste(fmt(ad), collapse='\n'), label = paste(estimator, collapse='\n'), x = if(estimand == 'p90') 60 else 25, y = if(estimand == 'p90') 5.5 else 6.2), by=.(estimand)]ggplot() + geom_line(aes(x=age, y=y, col=estimator), data=r[estimator != 'empirical']) + geom_point(aes(x=age, y=y, alpha=I(0.35)), data=r[estimator == 'empirical']) + facet_wrap(~ estimand) + geom_text(aes(x=x, y=y, label=label, hjust='left', size=I(3)), data=mad2) + geom_text(aes(x=x+10, y=y, label=value, hjust='left', size=I(3)), data=mad2) + guides(color=guide_legend(title='')) + theme(legend.position='bottom')````r ipacue()`It can be seen in @fig-cony-comparemany that modelsdedicated to a specific task (quantile regression for quantiles andOLS for means) were best for those tasks.Although the log-log ordinal cumulative probability model did notestimate the median as accurately as some other methods, it does wellfor the 0.75 and 0.9 quantiles and is the best compromise overall becauseof its ability to also directly predict the mean as well as quantitiessuch as $\Pr[\text{HbA}_{1c} > 7 | X]$.For here on we focus on the log-log ordinal model.Going back to the bottom left of `r ipacue()`@fig-cony-lookdist, let's look at quantile groupsof predicted `r hba` by OLS and plot predicted distributions of actual`r hba` against empirical distributions.```{r predobs,w=5.5,h=5,cap='Observed (dashed lines, open circles) and predicted (solid lines, closed circles) exceedance probability distributions from a model using 6-tiles of OLS-predicted $\\text{HbA}_{1c}$. Key shows quantile group intervals of predicted mean $\\text{HbA}_{1c}$.',scap='Observed and predicted distributions'}#| label: fig-cony-predobs###w$pghg <- cut2(pgh, g=6)f <- orm(gh ~ pgh6, family=loglog, data=w)lp <- predict(f, newdata=data.frame(pgh6=levels(w$pgh6)))ep <- ExProb(f) # Exceedance prob. functn. generator in rmsz <- ep(lp)j <- order(w$pgh6) # puts in order of lp (levels of pghg)plot(z, xlim=c(4, 7.5), data=w[j,c('pgh6', 'gh')]) ```Agreement between predicted and observed exceedance probabilitydistributions is excellent in @fig-cony-predobs.To return to the `r ipacue()` initial look at a linear model with assumed Gaussianresiduals, fit a probit ordinal model and compare the estimatedintercepts to the linear relationship with `gh` that is assumed bythe normal distribution.```{r lookprobit,cap='Estimated intercepts from probit model'}#| label: fig-cony-lookprobit#| fig-height: 2.75#| fig-width: 3.5spar(bty='l')f <- orm(gh ~ rcs(age,6), family=probit, data=w)g <- ols(gh ~ rcs(age,6), data=w)s <- g$stats['Sigma']yu <- f$yunique[-1]r <- quantile(w$gh, c(.005, .995))alphas <- coef(f)[1:num.intercepts(f)]plot(-yu / s, alphas, type='l', xlim=rev(- r / s), xlab=expression(-y/hat(sigma)), ylab=expression(alpha[y]))```@fig-cony-lookprobit depicts a significantdeparture from that implied by Gaussian residuals.### Examination of BMI`r mrg(sound("ord-cont-7"))`Using the log-log model, we first check the adequacy of BMI as asummary of height and weight for estimating median `gh`.* Adjust for age (without assuming linearity) in every case `r ipacue()`* Look at ratio of coefficients of log height and log weight* Use AIC to judge whether BMI is an adequate summary of height and weight```{r htwtcoef}f <- orm(gh ~ rcs(age,5) + log(ht) + log(wt), family=loglog, data=w)f``````{r aichtwt}aic <- NULLfor(mod in list(gh ~ rcs(age,5) + rcs(log(bmi),5), gh ~ rcs(age,5) + rcs(log(ht),5) + rcs(log(wt),5), gh ~ rcs(age,5) + rcs(log(ht),4) * rcs(log(wt),4))) aic <- c(aic, AIC(orm(mod, family=loglog, data=w)))print(aic)```The ratio of the coefficient of log height `r ipacue()` to the coefficient of logweight is `r round(coef(f)['ht']/coef(f)['wt'],1)`, which isbetween what BMI uses and the more dimensionally reasonableweight / height$^{3}$. By AIC, a spline interactionsurface between height and weight does slightly better than BMI inpredicting `r hba`, but a nonlinear function of BMI is barely worse. Itwill require other body size measures to displace BMI as a predictor.As an aside, compare this model fit to that from the Cox proportionalhazards model.The Cox model uses a conditioning argument to obtain a partiallikelihood free of the intercepts $\alpha$ (and requires a secondstep to estimate these log discrete hazard components) whereas we areusing a full marginal likelihood of the ranks of $Y$ [@kal73].```{r coxhtwtcoef}cph(Surv(gh) ~ rcs(age,5) + log(ht) + log(wt), data=w)```Back up and look at all body size measures, and examine theirredundancies. `r ipacue()````{r redun,h=6,w=6,cap='Variable clustering for all potential predictors'}#| label: fig-cony-redunv <- varclus(~ wt + ht + bmi + leg + arml + armc + waist + tri + sub + age + sex + re, data=w)plot(v) # Omit wt so it won't be removed before bmir <- redun(~ ht + bmi + leg + arml + armc + waist + tri + sub, data=w, r2=.75)rr2describe(r$scores, nvmax=5) # show strongest predictors of each variable```Six size measures adequately capture the entire set. Height and BMIare removed.An advantage of removing height `r ipacue()` is that it is age-dependent inthe elderly:```{r htchange,cap="Estimated median height as a smooth function of age, allowing age to interact with sex, from a proportional odds model",scap="Median height vs. age"}#| label: fig-cony-htchangef <- orm(ht ~ rcs(age,4)*sex, data=w) # Prop. odds modelqu <- Quantile(f); med <- function(x) qu(.5, x)ggplot(Predict(f, age, sex, fun=med, conf.int=FALSE), ylab='Predicted Median Height, cm')```**But** also see a change in leg length:```{r legchange,cap="Estimated median upper leg length as a smooth function of age, allowing age to interact with sex, from a proportional odds model",scap="Median leg length vs. age"}#| label: fig-cony-legchangef <- orm(leg ~ rcs(age,4)*sex, data=w)qu <- Quantile(f); med <- function(x) qu(.5, x)ggplot(Predict(f, age, sex, fun=med, conf.int=FALSE), ylab='Predicted Median Upper Leg Length, cm')```Next allocate d.f. according to generalized Spearman `r ipacue()``r mrg(sound("ord-cont-8"))`$\rho^{2}$ ^[Competition between collinear size measures hurts interpretation of partial tests of association in a saturated additive model.].```{r allocadf,h=3, w=4,cap='Generalized squared rank correlations'}#| label: fig-cony-allocadfspar(top=1, ps=9)s <- spearman2(gh ~ age + sex + re + wt + leg + arml + armc + waist + tri + sub, data=w, p=2)plot(s)```Parameters will be allocated in descending order of $\rho^2$. Butnote that subscapular skinfold has a large number of `NA`s andother predictors also have `NA`s. Suboptimal casewise deletionwill be used until the final model is fitted.Because there are many competing `r ipacue()` body measures, we use backwardsstepdown to arrive at a set of predictors. The bootstrap will be usedto penalize predictive ability for variable selection. First the fullmodel is fit usingcasewise deletion, then we do a composite test to assess whether anyof the frequently-missing predictors is important. Use likelihood ratio $\chi^2$ tests.```{r fitfullcasewise}f <- orm(gh ~ rcs(age,5) + sex + re + rcs(wt,3) + rcs(leg,3) + arml + rcs(armc,3) + rcs(waist,4) + tri + rcs(sub,3), family=loglog, data=w, x=TRUE, y=TRUE)print(f, coefs=FALSE)## Composite test:anova(f, leg, arml, armc, waist, tri, sub, test='LR')```<!-- s <- f$stats---><!-- cat(sprintf('{<br>tszs$n=%g, p=%g, g=%g, <br>rho=%g$}',---><!-- s['Obs'], s['d.f.'], round(s['g'],3),---><!-- round(s['rho'], 3)), '\n')--->The model yields Spearman $\rho=`r round(f$stats['rho'],3)`$, therank correlation between predicted and observed `r hba`.Show predicted mean and median `r hba``r ipacue()` as a function of age, adjustingother variables to median/mode. Compare the estimate of the medianwith that from quantile regression (discussed below).```{r casewisemeanmed,h=4,w=5,cap='Estimated mean and 0.5 and 0.9 quantiles from the log-log ordinal model using casewise deletion, along with predictions of 0.5 and 0.9 quantiles from quantile regression (QR). Age is varied and other predictors are held constant to medians/modes.',scap='Estimated mean and quantiles from casewise deletion model.'}#| label: fig-cony-casewisemeanmedM <- Mean(f)qu <- Quantile(f)med <- function(x) qu(.5, x)p90 <- function(x) qu(.9, x)fq <- Rq(formula(f), data=w)fq90 <- Rq(formula(f), data=w, tau=.9)pmean <- Predict(f, age, fun=M, conf.int=FALSE)pmed <- Predict(f, age, fun=med, conf.int=FALSE)p90 <- Predict(f, age, fun=p90, conf.int=FALSE)pmedqr <- Predict(fq, age, conf.int=FALSE)p90qr <- Predict(fq90, age, conf.int=FALSE)z <- rbind('orm mean'=pmean, 'orm median'=pmed, 'orm P90'=p90, 'QR median'=pmedqr, 'QR P90'=p90qr)ggplot(z, groups='.set.', adj.subtitle=FALSE, legend.label=FALSE)```Next do fast backward step-down `r ipacue()` in an attempt to get a model without so much competition among variables. The stepwise selection will be penalized for in the model validation. `r mrg(sound("ord-cont-9"))````{r prbw}print(fastbw(f, rule='p'), estimates=FALSE)```Validate the model, `r ipacue()` properly penalizing for variable selection```{r valbworm}g <- function() { set.seed(13) # so can reproduce results validate(f, B=100, bw=TRUE, estimates=FALSE, rule='p')}v <- runifChanged(g)``````{r prval}# Show number of variables selected in first 30 bootsprint(v, B=30)```Develop multiple imputations then repeat the bootstrap validation process, but separately for each completed dataset. The overall validation averages the bootstrap-corrected model performance measures over five validations.```{r aregi}set.seed(11)a <- aregImpute(~ gh + age + sex + re + wt + leg + arml + armc + waist + tri + sub, data=w, n.impute=5, pr=FALSE)av <- function(fit) list(validate=validate(fit, B=100, bw=TRUE, estimates=FALSE, prmodsel=FALSE, rule='p', pr=FALSE))h <- function() fit.mult.impute(gh ~ rcs(age,5) + sex + re + rcs(wt,3) + rcs(leg,3) + arml + rcs(armc,3) + rcs(waist,4) + tri + rcs(sub,3), orm, a, data=w, fun=v, fitargs=list(x=TRUE, y=TRUE, family='loglog'), pr=FALSE)f <- runifChanged(h, a, v) # 11mprint(processMI(f, 'validate'), B=10, digits=3)```There is no `calibrate` method for `orm` model fits. Next fit the reduced model. Use multiple imputation to impute missing`r ipacue()` predictors.Do a LR ANOVA for the reduced model, `r ipacue()` taking imputation into account.```{r sanova}h <- function() fit.mult.impute(gh ~ rcs(age,5) + re + rcs(leg,3) + rcs(waist,4) + tri + rcs(sub,4), orm, a, fitargs=list(family='loglog'), lrt=TRUE, data=w, pr=FALSE)g <- runifChanged(h, a)gan <- processMI(g, 'anova')# Show penalty-type parameters for imputationprmiInfo(an)# Correct likelihood-based statistics for imputationg <- LRupdate(g, an)print(an, caption='ANOVA for reduced model after multiple imputation, with addition of a combined effect for four size variables')b <- anova(g, leg, waist, tri, sub)# Add new lines to the plot with combined effect of 4 size var.s <- rbind(an, size=b['TOTAL', ])class(s) <- 'anova.rms'``````{r sanovaplot,cap="ANOVA for reduced model after multiple imputation"}#| label: fig-cony-sanova#| fig-height: 3spar(top=1)plot(s)````r ipacue()``r mrg(sound("ord-cont-10"))````{r peffects,cap='Partial effects (log hazard or log-log cumulative probability scale) of all predictors in reduced model, after multiple imputation',scap='Partial effects after multiple imputation',w=6.75,h=4.5}#| label: fig-cony-peffectsggplot(Predict(g), abbrev=TRUE, ylab=NULL) ````r ipacue()````{r mpeffects,cap='Partial effects (mean scale) of all predictors in reduced model, after multiple imputation',scap='Partial effects (means) after multiple imputation',w=6.75,h=4.5}#| label: fig-cony-mpeffectsM <- Mean(g)ggplot(Predict(g, fun=M), abbrev=TRUE, ylab=NULL) ```Compare the estimated age `r ipacue()` partial effects and confidence intervalswiththose from a model using casewise deletion, and with bootstrapnonparametric confidence intervals (also with casewise deletion).```{r cfmissmeth}h <- function() { gc <- orm(gh ~ rcs(age,5) + re + rcs(leg,3) + rcs(waist,4) + tri + rcs(sub,4), family=loglog, data=w, x=TRUE, y=TRUE) gb <- bootcov(gc, B=300) list(gc=gc, gb=gb)}gbc <- runifChanged(h)gc <- gbc$gcgb <- gbc$gb``````{r peffects2,cap='Partial effect for age from multiple imputation and casewise deletion (center lines with the green line depicting all non-multiple-imputation methods) with symmetric Wald 0.95 confidence bands using casewise deletion, basic bootstrap confidence bands using casewise deletion, percentile bootstrap confidence bands using casewise deletion, and symmetric Wald confidence bands accounting for multiple imputation.',scap='Partial effect for age with bootstrap and Wald confidence bands',w=5,h=4}#| label: fig-cony-peffects2pgc <- Predict(gc, age)bootclb <- Predict(gb, age, boot.type='basic')bootclp <- Predict(gb, age, boot.type='percentile')multimp <- Predict(g, age)p <- rbind('casewise deletion' = pgc, 'basic bootstrap' = bootclb, 'percentile bootstrap' = bootclp, 'multiple imputation' = multimp)[, .q(age, yhat, lower, upper, .set.)]m <- melt(p, id.vars=c('age', '.set.'))ggplot(m, aes(x=age, y=value, color=.set., group=paste(variable, .set.))) + geom_line() + guides(color=guide_legend(title='')) + theme(legend.position='bottom') + ylab(expression(X * hat(beta)))```In OLS `r ipacue()` the mean equals the median and both are linearly related to anyother quantiles. Semiparametric models are not this restrictive:`r mrg(sound("ord-cont-11"))````{r meanvs,cap='Predicted mean `r hba` vs. predicted median and 0.9 quantile along with their marginal distributions',scap='Predicted mean, median, and 0.9 quantile of `r hba`',w=4.5,h=3.5}#| label: fig-cony-meanvsM <- Mean(g)qu <- Quantile(g)med <- function(lp) qu(.5, lp)q90 <- function(lp) qu(.9, lp)lp <- predict(g)lpr <- quantile(predict(g), c(.002, .998), na.rm=TRUE)lps <- seq(lpr[1], lpr[2], length=200)pmn <- M(lps)pme <- med(lps)p90 <- q90(lps)plot(pmn, pme, xlab=expression(paste('Predicted Mean ', HbA["1c"])), ylab='Median and 0.9 Quantile', type='l', xlim=c(4.75, 8.0), ylim=c(4.75, 8.0), bty='n')box(col=gray(.8))lines(pmn, p90, col='blue')abline(a=0, b=1, col=gray(.8))text(6.5, 5.5, 'Median')text(5.5, 6.3, '0.9', col='blue')nint <- 350scat1d(M(lp), nint=nint)scat1d(med(lp), side=2, nint=nint)scat1d(q90(lp), side=4, col='blue', nint=nint)```Draw a nomogram `r ipacue()` to compute 7 different predicted values for eachsubject.```{r nomogram,cap='Nomogram for predicting median, mean, and 0.9 quantile of glycohemoglobin, along with the estimated probability that $\\text{HbA}_{1c} \\ge 6.5, 7$, or $7.5$, all from the log-log ordinal model',scap='Nomogram of log-log ordinal model for $\\text{HbA}_{1c}$',w=6.75,h=6.25}#| label: fig-cony-nomogramspar(ps=9)g <- Newlevels(g, list(re=abbreviate(levels(w$re))))exprob <- ExProb(g)nom <- nomogram(g, fun=list(Mean=M, 'Median Glycohemoglobin' = med, '0.9 Quantile' = q90, 'Prob(HbA1c >= 6.5)'= function(x) exprob(x, y=6.5), 'Prob(HbA1c >= 7.0)'= function(x) exprob(x, y=7), 'Prob(HbA1c >= 7.5)'= function(x) exprob(x, y=7.5)), fun.at=list(seq(5, 8, by=.5), c(5,5.25,5.5,5.75,6,6.25), c(5.5,6,6.5,7,8,10,12,14), c(.01,.05,.1,.2,.3,.4), c(.01,.05,.1,.2,.3,.4), c(.01,.05,.1,.2,.3,.4)))plot(nom, lmgp=.28) ``````{r echo=FALSE}saveCap('15')```