Multivariate elliptically-contoured repeated measurements models for linear and nonlinear changes over time in the presence of time-varying covariates and with AR(1) and two levels of variance components

Usage

elliptic(response, model="linear", times=NULL, dose=NULL, ccov=NULL,
	tvcov=NULL, nest=NULL, torder=0, interaction=NULL,
	transform="identity", link="identity", autocorr="exponential",
	pell=NULL, preg=rep(1,4), pvar=var(y), varfn=NULL, pre=NULL,
	par=NULL, delta=NULL, envir=sys.frame(sys.parent()),
	print.level=0, gradtol=0.00001, typsiz=abs(theta),
	stepmax=10*sqrt(theta%*%theta), steptol=0.00001,
	iterlim=100, ndigit=10, fscale=1)

Arguments

response A list of two or three column matrices with response values, times, and possibly nesting categories, for each individual, one matrix or dataframe of response values, or an object of class, response (created by restovec) or repeated (created by rmna).
model The model to be fitted for the location. Builtin choices are (1) linear for linear models with time-varying covariate; if torder > 0, a polynomial in time is automatically fitted; (2) logistic for a four-parameter logistic growth curve; (3) pkpd for a first-order one-compartment pharmacokinetic model. Otherwise, set this to a function of the parameters or a formula beginning with ~, specifying either a linear regression function for the location parameter in the Wilkinson and Rogers notation or a general function with named unknown parameters that describes the location, returning a vector the same length as the number of observations, in which case ccov and tvcov cannot be used.
times When response is a matrix, a vector of possibly unequally spaced times when they are the same for all individuals or a matrix of times. Not necessary if equally spaced. Ignored if response has class, response or repeated.
dose A vector of dose levels for the pkpd model, one per individual.
ccov A vector or matrix containing time-constant baseline covariates with one line per individual, a model formula using vectors of the same size, or an object of class, tccov (created by tcctomat). For the pkpd and logistic models, all variables must be binary (or factor variables) as different values of all parameters are calculated for all combinations of these variables (except for the logistic model when a time-varying covariate is present). Cannot be used when model is a function. Ignored if response has class, repeated.
tvcov A list of vectors or matrices with time-varying covariates for each individual (one column per variable), a matrix or dataframe of such covariate values (if only one covariate), or an object of class, tvcov (created by tvctomat). If times are not the same as for responses, the list can be created with gettvc. Only one time-varying covariate is allowed except for the linear model; if more are required, set model equal to the appropriate mean function. This argument cannot be used when model is a function and is ignored if response has class, repeated.
nest When response is a matrix, a vector of length equal to the number of responses per individual indicating which responses belong to which nesting category. Categoriess must be consecutive increasing integers. This option should always be specified if nesting is present. Ignored if response has class, repeated.
torder When the linear model is chosen, order of the polynomial in time to be fitted.
interaction Vector of length equal to the number of time-constant covariates, giving the levels of interactions between them and the polynomial in time in the linear model.
transform Transformation of the response variable: identity, exp, square, sqrt, or log.
link Link function for the location: identity, exp, square, sqrt, or log. For the linear model, if not the identity, initial estimates of the regression parameters must be supplied (intercept, polynomial in time, time-constant covariates, time-varying covariates, in that order).
autocorr The form of the autocorrelation function: exponential is the usual rho^|t_i-t_j|; gaussian is rho^((t_i-t_j)^2); cauchy is 1/(1+rho(t_i-t_j)^2); spherical is ((|t_i-t_j|rho)^3-3|t_i-t_j|rho+2)/2 for |t_i-t_j|<=1/rho and zero otherwise; IOU is the integrated Ornstein-Uhlenbeck process, (2rho min(t_i,t_j)+exp(-rho t_i) +exp(-rho t_j)-1 -exp(rho|ti-t_j|))/2rho^3.
pell Initial estimate of the power parameter of the multivariate elliptically-contoured distribution. If missing, the multivariate normal distribution is used.
preg Initial parameter estimates for the regression model. Only required for linear model if the link is not the identity or a variance function is fitted.
pvar Initial parameter estimate for the variance. If more than one value is provided, the log variance depends on a polynomial in time. With the pkpd model, if four values are supplied, a nonlinear regression for the variance is fitted.
varfn The builtin variance function has the variance proportional to a function of the location: pvar*v(mu) = identity or square. If pvar contains two initial values, an additive constant is included: pvar(1)+pvar(2)*v(mu). Otherwise, either a function or a formula beginning with ~, specifying either a linear regression function in the Wilkinson and Rogers notation or a general function with named unknown parameters for the log variance can be supplied, yielding a vector the same length as the number of observations.
pre Zero, one or two parameter estimates for the variance components, depending on the number of levels of nesting.
par If supplied, an initial estimate for the autocorrelation parameter.
delta Scalar or vector giving the unit of measurement for each response value, set to unity by default. For example, if a response is measured to two decimals, delta=0.01. Ignored if response has class, response or repeated.
envir Environment in which model formulae are to be interpreted or a data object of class, repeated, tccov, or tvcov.
others Arguments controlling nlm.

Description

elliptic fits a special case of the multivariate elliptically-contoured distribution, called the multivariate power exponential distribution. It includes the multivariate normal (power=1), the multivariate Laplace (power=0.5), and the multivariate uniform (power -> infinity) distributions as special cases.

For clustered (non-longitudinal) data, where only random effects will be fitted, the `times' may be any strictly increasing sequence distinguishing the responses on an individual.

It is designed to fit linear and nonlinear models with time-varying covariates observed at arbitrary time points. A continuous-time AR(1) and zero, one, or two levels of nesting can be handled.

Nonlinear regression models can be supplied as formulae where parameters are unknowns. Factor variables cannot be used and parameters must be scalars. (See finterp.)

Value

A list of class elliptic is returned.

Author(s)

J.K. Lindsey

See Also

carma, finterp, gar, gettvc, glmm, gnlmm, gnlr, kalseries, potthoff, read.list, restovec, rmna, tcctomat, tvctomat.

Examples

# linear models
y <- matrix(rnorm(40),ncol=5)
x1 <- gl(2,4)
x2 <- gl(2,1,8)
# independence with time trend
elliptic(y, ccov=~x1, torder=2)
# AR(1)
elliptic(y, ccov=~x1, torder=2, par=0.1)
elliptic(y, ccov=~x1, torder=3, interact=3, par=0.1)
# random intercept
elliptic(y, ccov=~x1+x2, interact=c(2,0), torder=3, pre=2)
#
# nonlinear models
times <- rep(1:20,2)
dose <- c(rep(2,20),rep(5,20))
mu <- function(p) exp(p[1]-p[3])*(dose/(exp(p[1])-exp(p[2]))*
	(exp(-exp(p[2])*times)-exp(-exp(p[1])*times)))
shape <- function(p) exp(p[1]-p[2])*times*dose*exp(-exp(p[1])*times)
conc <- matrix(rnorm(40,mu(log(c(1,0.3,0.2))),sqrt(shape(log(c(0.1,0.4))))),
	ncol=20,byrow=T)
conc[,2:20] <- conc[,2:20]+0.5*(conc[,1:19]-matrix(mu(log(c(1,0.3,0.2))),
	ncol=20,byrow=T)[,1:19])
conc <- ifelse(conc>0,conc,0.01)
# with builtin function
# independence
elliptic(conc, model="pkpd", preg=log(c(0.5,0.4,0.1)), dose=c(2,5))
# AR(1)
elliptic(conc, model="pkpd", preg=log(c(0.5,0.4,0.1)), dose=c(2,5),
	par=0.1)
# add variance function
elliptic(conc, model="pkpd", preg=log(c(0.5,0.4,0.1)), dose=c(2,5),
	par=0.1, varfn=shape, pvar=log(c(0.5,0.2)))
# multivariate elliptical distribution
elliptic(conc, model="pkpd", preg=log(c(0.5,0.4,0.1)), dose=c(2,5),
	par=0.1, varfn=shape, pvar=log(c(0.5,0.2)), pell=1)
# or equivalently with user-specified function
# independence
elliptic(conc, model=mu, preg=log(c(0.5,0.4,0.1)))
# AR(1)
elliptic(conc, model=mu, preg=log(c(0.5,0.4,0.1)), par=0.1)
# add variance function
elliptic(conc, model=mu, preg=log(c(0.5,0.4,0.1)), par=0.1,
	varfn=shape, pvar=log(c(0.5,0.2)))
# multivariate elliptical distribution
elliptic(conc, model=mu, preg=log(c(0.5,0.4,0.1)), par=0.1,
	varfn=shape, pvar=log(c(0.5,0.2)), pell=1)
# or with user-specified formula
# independence
elliptic(conc, model=~exp(absorption-volume)*
	dose/(exp(absorption)-exp(elimination))*
	(exp(-exp(elimination)*times)-exp(-exp(absorption)*times)),
	preg=list(absorption=log(0.5),elimination=log(0.4),
	volume=log(0.1)))
# AR(1)
elliptic(conc, model=~exp(absorption-volume)*
	dose/(exp(absorption)-exp(elimination))*
	(exp(-exp(elimination)*times)-exp(-exp(absorption)*times)),
	preg=list(absorption=log(0.5),elimination=log(0.4),volume=log(0.1)),
	par=0.1)
# add variance function
elliptic(conc, model=~exp(absorption-volume)*
	dose/(exp(absorption)-exp(elimination))*
	(exp(-exp(elimination)*times)-exp(-exp(absorption)*times)),
	preg=list(absorption=log(0.5),elimination=log(0.4),volume=log(0.1)),
	varfn=~exp(b1-b2)*times*dose*exp(-exp(b1)*times),
	par=0.1, pvar=list(b1=log(0.5),b2=log(0.2)))
# multivariate elliptical distribution
elliptic(conc, model=~exp(absorption-volume)*
	dose/(exp(absorption)-exp(elimination))*
	(exp(-exp(elimination)*times)-exp(-exp(absorption)*times)),
	preg=list(absorption=log(0.5),elimination=log(0.4),volume=log(0.1)),
	varfn=~exp(b1-b2)*times*dose*exp(-exp(b1)*times),
	par=0.1, pvar=list(b1=log(0.5),b2=log(0.2)), pell=1)
#
# generalized logistic regression with square-root transformation
# and square  link
times <- rep(seq(10,200,by=10),2)
mu <- function(p) {
	yinf <- exp(p[2])
	yinf*(1+((yinf/exp(p[1]))^p[4]-1)*exp(-yinf^p[4]
		*exp(p[3])*times))^(-1/p[4])}
y <- matrix(rnorm(40,sqrt(mu(c(2,1.5,0.05,-2))),0.05)^2,ncol=20,byrow=T)
y[,2:20] <- y[,2:20]+0.5*(y[,1:19]-matrix(mu(c(2,1.5,0.05,-2)),
	ncol=20,byrow=T)[,1:19])
y <- ifelse(y>0,y,0.01)
# with builtin function
# independence
elliptic(y, model="logistic", preg=c(2,1,0.1,-1), trans="sqrt",
	link="square")
# the same model with AR(1)
elliptic(y, model="logistic", preg=c(2,1,0.1,-1), trans="sqrt",
	link="square", par=0.4)
# the same model with AR(1) and one component of variance
elliptic(y, model="logistic", preg=c(2,1,0.1,-1),
	trans="sqrt", link="square", pre=1, par=0.4)
# or equivalently with user-specified function
# independence
elliptic(y, model=mu, preg=c(2,1,0.1,-1), trans="sqrt",
	link="square")
# the same model with AR(1)
elliptic(y, model=mu, preg=c(2,1,0.1,-1), trans="sqrt",
	link="square", par=0.4)
# the same model with AR(1) and one component of variance
elliptic(y, model=mu, preg=c(2,1,0.1,-1),
	trans="sqrt", link="square", pre=1, par=0.4)
# or equivalently with user-specified formula
# independence
elliptic(y, model=~exp(yinf)*(1+((exp(yinf-y0))^b4-1)*
	exp(-exp(yinf*b4+b3)*times))^(-1/b4),
	preg=list(y0=2,yinf=1,b3=0.1,b4=-1), trans="sqrt", link="square")
# the same model with AR(1)
elliptic(y, model=~exp(yinf)*(1+((exp(yinf-y0))^b4-1)*
	exp(-exp(yinf*b4+b3)*times))^(-1/b4),
	preg=list(y0=2,yinf=1,b3=0.1,b4=-1), trans="sqrt",
	link="square", par=0.1)
# add one component of variance
elliptic(y, model=~exp(yinf)*(1+((exp(yinf-y0))^b4-1)*
	exp(-exp(yinf*b4+b3)*times))^(-1/b4),
	preg=list(y0=2,yinf=1,b3=0.1,b4=-1),
	trans="sqrt", link="square", pre=1, par=0.1)
#
# multivariate elliptical distribution for outliers
y <- matrix(rcauchy(40,mu(c(2,1.5,0.05,-2)),0.05),ncol=20,byrow=T)
y[,2:20] <- y[,2:20]+0.5*(y[,1:19]-matrix(mu(c(2,1.5,0.05,-2)),
	ncol=20,byrow=T)[,1:19])
y <- ifelse(y>0,y,0.01)
# first with normal distribution
elliptic(y, model="logistic", preg=c(1,1,0.1,-1))
elliptic(y, model="logistic", preg=c(1,1,0.1,-1), par=0.5)
# then elliptic
elliptic(y, model="logistic", preg=c(1,1,0.1,-1), pell=1)
elliptic(y, model="logistic", preg=c(1,1,0.1,-1), par=0.5, pell=1)


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