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#' Fit Semiparametric Proportional 0dds Model
#'
#' Fits a semiparametric proportional odds model: \deqn{ logit(1-S_Z(t)) =
#' log(G(t)) + \beta^T Z }{} where G(t) is increasing but otherwise unspecified.
#' Model is fitted by maximising the modified partial likelihood. A
#' goodness-of-fit test by considering the score functions is also computed by
#' resampling methods.
#'
#' The modelling formula uses the standard survival modelling given in the
#' \bold{survival} package.
#'
#' For large data sets use the divide.conquer.timereg of the mets package to
#' run the model on splits of the data, or the alternative estimator by the
#' cox.aalen function.
#'
#' The data for a subject is presented as multiple rows or "observations", each
#' of which applies to an interval of observation (start, stop]. The program
#' essentially assumes no ties, and if such are present a little random noise
#' is added to break the ties.
#'
#' @param formula a formula object, with the response on the left of a '~'
#' operator, and the terms on the right. The response must be a Event object
#' as returned by the `Event' function.
#' @param data a data.frame with the variables.
#' @param start.time start of observation period where estimates are computed.
#' @param max.time end of observation period where estimates are computed.
#' Estimates thus computed from [start.time, max.time]. This is very useful to
#' obtain stable estimates, especially for the baseline. Default is max of
#' data.
#' @param id For timevarying covariates the variable must associate each record
#' with the id of a subject.
#' @param n.sim number of simulations in resampling.
#' @param weighted.test to compute a variance weighted version of the
#' test-processes used for testing time-varying effects.
#' @param beta starting value for relative risk estimates
#' @param Nit number of iterations for Newton-Raphson algorithm.
#' @param detail if 0 no details is printed during iterations, if 1 details are
#' given.
#' @param profile if profile is 1 then modified partial likelihood is used,
#' profile=0 fits by simple estimating equation. The modified partial
#' likelihood is recommended.
#' @param sym to use symmetrized second derivative in the case of the
#' estimating equation approach (profile=0). This may improve the numerical
#' performance.
#' @param baselinevar set to 0 to omit calculations of baseline variance.
#' @param clusters to compute cluster based standard errors.
#' @param max.clust number of maximum clusters to be used, to save time in iid
#' decomposition.
#' @param weights weights for score equations.
#' @return returns an object of type 'cox.aalen'. With the following arguments:
#'
#' \item{cum}{cumulative timevarying regression coefficient estimates are
#' computed within the estimation interval.} \item{var.cum}{the martingale
#' based pointwise variance estimates. } \item{robvar.cum}{robust pointwise
#' variances estimates. } \item{gamma}{estimate of proportional odds
#' parameters of model.} \item{var.gamma}{variance for gamma. }
#' \item{robvar.gamma}{robust variance for gamma. } \item{residuals}{list with
#' residuals. Estimated martingale increments (dM) and corresponding time
#' vector (time).} \item{obs.testBeq0}{observed absolute value of supremum of
#' cumulative components scaled with the variance.}
#' \item{pval.testBeq0}{p-value for covariate effects based on supremum test.}
#' \item{sim.testBeq0}{resampled supremum values.} \item{obs.testBeqC}{observed
#' absolute value of supremum of difference between observed cumulative process
#' and estimate under null of constant effect.} \item{pval.testBeqC}{p-value
#' based on resampling.} \item{sim.testBeqC}{resampled supremum values.}
#' \item{obs.testBeqC.is}{observed integrated squared differences between
#' observed cumulative and estimate under null of constant effect.}
#' \item{pval.testBeqC.is}{p-value based on resampling.}
#' \item{sim.testBeqC.is}{resampled supremum values.}
#' \item{conf.band}{resampling based constant to construct robust 95\% uniform
#' confidence bands. } \item{test.procBeqC}{observed test-process of difference
#' between observed cumulative process and estimate under null of constant
#' effect over time.} \item{loglike}{modified partial likelihood, pseudo
#' profile likelihood for regression parameters.} \item{D2linv}{inverse of the
#' derivative of the score function.} \item{score}{value of score for final
#' estimates.} \item{test.procProp}{observed score process for proportional
#' odds regression effects.} \item{pval.Prop}{p-value based on resampling.}
#' \item{sim.supProp}{re-sampled supremum values.}
#' \item{sim.test.procProp}{list of 50 random realizations of test-processes
#' for constant proportional odds under the model based on resampling.}
#' @author Thomas Scheike
#' @references Martinussen and Scheike, Dynamic Regression Models for Survival
#' Data, Springer (2006).
#' @keywords survival
#' @examples
#'
#' data(sTRACE)
#' # Fits Proportional odds model
#' out<-prop.odds(Event(time,status==9)~age+diabetes+chf+vf+sex,
#' sTRACE,max.time=7,n.sim=100)
#' summary(out)
#'
#' par(mfrow=c(2,3))
#' plot(out,sim.ci=2)
#' plot(out,score=1)
#'
#' pout <- predict(out,Z=c(70,0,0,0,0))
#' plot(pout)
#'
#' ### alternative estimator for large data sets
#' form <- Surv(time,status==9)~age+diabetes+chf+vf+sex
#' pform <- timereg.formula(form)
#' out2<-cox.aalen(pform,data=sTRACE,max.time=7,
#' propodds=1,n.sim=0,robust=0,detail=0,Nit=40)
#' summary(out2)
#'
#' @export
prop.odds<-function(formula,data=parent.frame(),beta=NULL,
Nit=20,detail=0,start.time=0,max.time=NULL,id=NULL,n.sim=500,weighted.test=0,
profile=1,sym=0,baselinevar=1,clusters=NULL,max.clust=1000,weights=NULL)
{ ## {{{
out <- prop.odds.subdist(formula,data=data,beta=beta,cause=1,
Nit=Nit,detail=detail,start.time=start.time,max.time=max.time,id=id,n.sim=n.sim,
weighted.test=weighted.test,
profile=profile,sym=sym,cens.model="po",clusters=clusters,max.clust=max.clust,baselinevar=1,weights=weights)
return(out);
} ## }}}
prop.odds.gam<-function(formula,data=parent.frame(),beta=NULL,
Nit=10,detail=0,start.time=0,max.time=NULL,id=NULL,n.sim=500,weighted.test=0,
profile=1,sym=0,baselinevar=1,clusters=NULL,max.clust=1000)
{ ## {{{
id.call<-id; call<-match.call(); residuals<-0;
robust<-0; ratesim<-0;
resample.iid <- 1 # profile<-0;
m<-match.call(expand.dots = FALSE);
m$sym<-m$profile<-m$max.time<-m$start.time<-m$weighted.test<-m$n.sim<-
m$id<-m$Nit<-m$detail<-m$beta <- m$baselinevar<-m$clusters <- m$max.clust <- NULL
if (n.sim==0) sim<-0 else sim<-1;
antsim<-n.sim;
Terms <- if(missing(data)) terms(formula)
else terms(formula, data=data)
m$formula <- Terms
m[[1]] <- as.name("model.frame")
m <- eval(m, parent.frame())
mt <- attr(m, "terms")
intercept<-attr(mt, "intercept")
Y <- model.extract(m, "response")
if (!inherits(Y, "Surv")) stop("Response must be a survival object")
if (attr(m[, 1], "type") == "right") {
time2 <- m[, 1][, "time"]; time <- rep(0,length(time2));
status <- m[, 1][, "status"] } else
if (attr(m[, 1], "type") == "counting") {
time <- m[, 1][,1]; time2 <- m[, 1][,2]; status <- m[, 1][,3]; } else {
stop("only right-censored or counting processes data") }
X <- model.matrix(Terms, m)[,-1,drop=FALSE]; covnamesX<-dimnames(X)[[2]];
desX<-as.matrix(X);
if(is.matrix(desX) == TRUE) pg <- as.integer(dim(desX)[2])
if(is.matrix(desX) == TRUE) nx <- as.integer(dim(desX)[1])
px<-1;
Ntimes <- sum(status);
# adds random noise to make survival times unique
if (sum(duplicated(time2[status==1]))>0) {
#cat("Non unique survival times: break ties ! \n")
#cat("Break ties yourself\n");
ties<-TRUE
dtimes<-time2[status==1]
index<-(1:length(time2))[status==1]
ties<-duplicated(dtimes); nties<-sum(ties); index<-index[ties]
dt<-diff(sort(time2)); dt<-min(dt[dt>0]);
time2[index]<-time2[index]+runif(nties,0,min(0.001,dt/2));
} else ties<-FALSE;
start<-time; stop<-time2;
dtimes<-time2[status==1];
times<-c(start.time,dtimes[dtimes>start.time]);
times<-sort(times);
if (is.null(max.time)==TRUE) maxtimes<-max(times)+0.1 else maxtimes<-max.time;
times<-times[times<=maxtimes]
Ntimes <- length(times);
if ((nrow(X)!=nrow(data)) && (!is.null(id))) stop("Missing values in design matrix not allowed with id\n");
### if (nrow(X)!=nrow(data)) stop("Missing values in design matrix not allowed\n");
########################################################################
if (is.null(id)==TRUE) {antpers<-length(time); id<-0:(antpers-1); }
else { pers<-unique(id); antpers<-length(pers);
id<-as.integer(factor(id,labels=1:(antpers)))-1;
}
cluster.call<-clusters;
if (is.null(clusters)== TRUE) {clusters<-id; antclust<-antpers;} else {
clus<-unique(clusters); antclust<-length(clus);
clusters <- as.integer(factor(clusters, labels = 1:(antclust))) - 1;
}
if ((!is.null(max.clust))) if (max.clust<antclust) {
qq <- unique(quantile(clusters, probs = seq(0, 1, by = 1/max.clust)))
qqc <- cut(clusters, breaks = qq, include.lowest = TRUE)
clusters <- as.integer(qqc)-1
max.clusters <- length(unique(clusters))
### clusters <- as.integer(factor(qqc, labels = 1:max.clust)) -1
antclust <- max.clust
}
if (resample.iid == 1) {
biid <- double(Ntimes* antclust );
gamiid<- double(antclust *pg);
} else {
gamiid <- biid <- NULL;
}
if ((length(beta)!=pg) && (is.null(beta)==FALSE)) beta <- rep(beta[1],pg);
if ((is.null(beta))) {
if ( (attr(m[, 1], "type") == "right" ) ) beta<-coxph(Surv(stop,status)~X)$coef
else beta<-coxph(Surv(start,stop,status)~X)$coef;
}
if (residuals==1) {
cumAi<-matrix(0,Ntimes,antpers*1);
cumAiiid<-matrix(0,Ntimes,antpers*1);
} else { cumAi<-0; cumAiiid<-0; }
cumint<-matrix(0,Ntimes,px+1);
vcum<-matrix(0,Ntimes,px+1);
Rvcu<-matrix(0,Ntimes,px+1);
score<-beta;
Varbeta<-matrix(0,pg,pg); Iinv<-matrix(0,pg,pg);
RVarbeta<-matrix(0,pg,pg);
if (sim==1) Uit<-matrix(0,Ntimes,50*pg) else Uit<-NULL;
test<-matrix(0,antsim,2*px); testOBS<-rep(0,2*px); unifCI<-c();
testval<-c();
rani<--round(runif(1)*10000);
Ut<-matrix(0,Ntimes,pg+1); simUt<-matrix(0,antsim,pg);
loglike<-0;
########################################################################
###cat("Proportional odds model \n");
###dyn.load("Gprop-odds.so")
nparout<- .C("transsurv",
as.double(times),as.integer(Ntimes),as.double(desX),
as.integer(nx),as.integer(pg),as.integer(antpers),
as.double(start),as.double(stop), as.double(beta),
as.integer(Nit), as.double(cumint), as.double(vcum),
as.double(Iinv),as.double(Varbeta),as.integer(detail),
as.integer(sim),as.integer(antsim),as.integer(rani),
as.double(Rvcu),as.double(RVarbeta),as.double(test),
as.double(testOBS),as.double(Ut),as.double(simUt),
as.double(Uit),as.integer(id),as.integer(status),
as.integer(weighted.test),as.integer(ratesim),as.double(score),
as.double(cumAi),as.double(cumAiiid),as.integer(residuals),
as.double(loglike),as.integer(profile),as.integer(sym),
as.integer(baselinevar),as.integer(clusters),as.integer(antclust),
as.double(biid),as.double(gamiid),PACKAGE="timereg");
gamma<-matrix(nparout[[9]],pg,1);
cumint<-matrix(nparout[[11]],Ntimes,px+1);
vcum<-matrix(nparout[[12]],Ntimes,px+1);
Iinv<-matrix(nparout[[13]],pg,pg);
Varbeta<--matrix(nparout[[14]],pg,pg);
Rvcu<-matrix(nparout[[19]],Ntimes,px+1);
RVarbeta<--matrix(nparout[[20]],pg,pg);
score<-matrix(nparout[[30]],pg,1);
Ut<-matrix(nparout[[23]],Ntimes,pg+1);
loglike<-nparout[[34]]
if (residuals==1) {
cumAi<-matrix(nparout[[31]],Ntimes,antpers*1);
cumAiiid<-matrix(nparout[[32]],Ntimes,antpers*1);
cumAi<-list(time=times,dmg=cumAi,dmg.iid=cumAiiid);} else cumAi<-NULL;
if (resample.iid==1) {
biid<-matrix(nparout[[40]],Ntimes,antclust);
gamiid<-matrix(nparout[[41]],antclust,pg)
gamiid <- t(Iinv %*% t(gamiid))
B.iid<-list();
for (i in (1:antclust)) {
B.iid[[i]]<-matrix(biid[,i],ncol=1);
colnames(B.iid[[i]])<-"Baselineiid";
}
colnames(gamiid)<-covnamesX
} else B.iid<-gamiid<-NULL;
if (sim==1) {
Uit<-matrix(nparout[[25]],Ntimes,50*pg); UIt<-list();
for (i in (0:49)*pg) UIt[[i/pg+1]]<-as.matrix(Uit[,i+(1:pg)]);
simUt<-matrix(nparout[[24]],antsim,pg);
test<-matrix(nparout[[21]],antsim,2*px); testOBS<-nparout[[22]];
supUtOBS<-apply(abs(as.matrix(Ut[,-1])),2,max);
for (i in 1:(2*px)) testval<-c(testval,pval(test[,i],testOBS[i]));
for (i in 1:px) unifCI<-c(unifCI,percen(test[,i],0.95));
testUt<-c();
for (i in 1:pg) testUt<-c(testUt,pval(simUt[,i],supUtOBS[i]));
pval.testBeq0<-as.vector(testval[1:px]);
pval.testBeqC<-as.vector(testval[(px+1):(2*px)]);
obs.testBeq0<-as.vector(testOBS[1:px]);
obs.testBeqC<-as.vector(testOBS[(px+1):(2*px)]);
sim.testBeq0<-as.matrix(test[,1:px]);
sim.testBeqC<-as.matrix(test[,(px+1):(2*px)]);
sim.supUt<-as.matrix(simUt);
}
if (sim!=1) {
testUt<-NULL;test<-NULL;unifCI<-NULL;supUtOBS<-NULL;UIt<-NULL;testOBS<-NULL;testval<-NULL;
pval.testBeq0<- pval.testBeqC<- obs.testBeq0<- obs.testBeqC<- sim.testBeq0<-
sim.testBeqC<-NULL; testUt<-NULL; sim.supUt<-NULL;
}
ud<-list(cum=cumint,var.cum=vcum,robvar.cum=Rvcu,
gamma=gamma,var.gamma=Varbeta,robvar.gamma=RVarbeta,
resid.dMG=cumAi,D2linv=Iinv,score=score,loglike=loglike,
pval.testBeq0=pval.testBeq0,pval.testBeqC=pval.testBeqC,
obs.testBeq0=obs.testBeq0,obs.testBeqC=obs.testBeqC,
sim.testBeq0= sim.testBeq0,sim.testBeqC=sim.testBeqC,
conf.band=unifCI,
test.procProp=Ut,sim.test.procProp=UIt,pval.Prop=testUt,
sim.supProp=sim.supUt,prop.odds=TRUE,gamma.iid=gamiid,B.iid=B.iid)
colnames(ud$cum)<-colnames(ud$var.cum)<- c("time","Baseline")
if (robust==1) colnames(ud$robvar.cum)<- c("time","Baseline");
if (px>0) {
if (sim==1) {
colnames(ud$test.procProp)<-c("time",covnamesX)
names(ud$pval.Prop)<-covnamesX
names(ud$conf.band)<-names(ud$pval.testBeq0)<-
names(ud$pval.testBeqC)<-names(ud$obs.testBeq0)<-
names(ud$obs.testBeqC)<-colnames(ud$sim.testBeq0)<-"Baseline";
} }
rownames(ud$gamma)<-c(covnamesX); colnames(ud$gamma)<-"estimate";
rownames(ud$score)<-c(covnamesX); colnames(ud$score)<-"score";
namematrix(ud$var.gamma,covnamesX);
namematrix(ud$robvar.gamma,covnamesX);
namematrix(ud$D2linv,covnamesX);
attr(ud,"Call")<-call;
attr(ud,"Formula")<-formula;
attr(ud,"id")<-id.call;
attr(ud,"basesim") <- 1
attr(ud,"type") <- "survival"
class(ud)<-"cox.aalen"
return(ud);
} ## }}}
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