1198 lines
48 KiB
Plaintext
1198 lines
48 KiB
Plaintext
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\documentclass{article}[11pt]
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\usepackage{Sweave}
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\usepackage{amsmath}
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\addtolength{\textwidth}{1in}
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\addtolength{\oddsidemargin}{-.5in}
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\setlength{\evensidemargin}{\oddsidemargin}
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\SweaveOpts{keep.source=TRUE, fig=FALSE}
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% Ross Ihaka suggestions
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\DefineVerbatimEnvironment{Sinput}{Verbatim} {xleftmargin=2em}
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\DefineVerbatimEnvironment{Soutput}{Verbatim}{xleftmargin=2em}
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\DefineVerbatimEnvironment{Scode}{Verbatim}{xleftmargin=2em}
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\fvset{listparameters={\setlength{\topsep}{0pt}}}
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\renewenvironment{Schunk}{\vspace{\topsep}}{\vspace{\topsep}}
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\SweaveOpts{prefix.string=adjcurve,width=6,height=4}
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\setkeys{Gin}{width=\textwidth}
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%\VignetteIndexEntry{Validation}
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<<init, echo=FALSE>>=
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options(continue=" ", width=60)
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options(SweaveHooks=list(fig=function() par(mar=c(4.1, 4.1, .3, 1.1))))
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pdf.options(pointsize=8) #text in graph about the same as regular text
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library(survival, quietly=TRUE)
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@
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\newcommand{\imat}{H} % use H for the hessian rather than script I
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\newcommand{\Cvar}{H^{-1}} % use H for the hessian rather than script I
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\newcommand{\splus}{R} % ``the survival package'' would be an alternate
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\newcommand{\xbar}{\overline x}
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\newcommand{\lhat}{\hat \Lambda}
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\def\bhat{\hat\beta} %define "bhat" to mean "beta hat"
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\def\Mhat{\widehat M} %define "Mhat" to mean M-hat
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\newcommand{\code}[1]{\texttt{#1}}
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\title{Software validation}
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\author{Terry M Therneau}
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\date{Dec 2022 (updated)}
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\begin{document}
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\maketitle
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\section{Introduction}
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\begin{quotation}
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`When I use a word,' Humpty Dumpty said, in rather a scornful tone,
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`it means just what I choose it to mean - neither more nor less.'
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`The question is,' said Alice, `whether you can make words mean so
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many different things.'
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`The question is,' said Humpty Dumpty, `which is to be master - that's all.'
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-Lewis Caroll, \emph{Through the Looking Glass}
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\end{quotation}
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``Validatation'' has become a Humpty-Dumpty word: it is used for many different
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things in
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scientific research that it has become essentially meaningless
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without further clarification.
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One of the more common meanings assigned to it in the software
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realm is ``repeatability'', i.e.
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that a new release of a given package or routine
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will give the same results as it did the week before.
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Users of the software often assume the word implies a more
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rigorous criterion, namely that the routine gives \emph{correct} answers.
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Validation of the latter type is rare, however;
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working out formally correct answers is boring, tedious work.
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This note contains a set of examples of this latter type.
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Although the data sets are very simple, the examples
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have proven extremely useful in debugging the methods, not least
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because all the intermediate steps of each calculation are transparent,
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and have been incorporated into the formal test suite for the
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survival package as the files \code{book1.R}, \code{book2.R}, etc. in the
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\code{tests} subdirectory.
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They also continue to be a resource for package's defence:
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I have been told multiple times that some person or group cannot use R
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in their work because ``SAS is validated'' while R is not.
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The survival package passes all of the tests below
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and SAS passes some but not all of them.
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It is my hope that the formal test cases will
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be a resource for developers on multiple platforms.
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Portions of this work were included as an appendix in
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the textbook of Therneau and Grambsch
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\cite{Therneau00} precisely for this reason.
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\section{Basic formulas}
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All these examples have a single covariate.
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Let $x_i$ be the covariate for each subject, $r_i= \exp(x_i \beta)$
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the risk score for the subject, and $w_i$ the case weight, if any.
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Let $Y_i(t)$ be 1 if subject $i$ is at risk at time $t$ and 0 otherwise,
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and $dN_i(t)$ be the death indicator which is 1 if subject $i$ has
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an event at time $t$.
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At each death time we have the following quantities:
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\begin{align}
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LPL(t) &= \frac{\sum_i dN_i(t) \log(r_i)}{\log\left( \sum_i Y_i(t) w_i r_i
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\right)} \\
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\xbar(t) &= \frac{\sum_i Y_i(t) w_i r_i x_i}{ \sum_i Y_i(t) w_i r_i}\\
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U(t) &= \sum_i dN_i(t) (x_i - \xbar(t)) \label{U1} \\
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H(t) &= \frac{\sum_i Y_i(t) (x_i - \xbar(t))^2}{\sum_i Y_i(t) w_i r_i}\\
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&= \frac{\sum_i Y_i(t) x_i^2}{\sum_i Y_i(t) w_i r_i}- \xbar(t)^2
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\label{H2} \\
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\lambda(t) &= \frac{\sum_i w_i dN_i(t)}{\sum_i Y_i(t) w_i r_i}
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\end{align}
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The denominator for all the sums is the weighted number of subjects who
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are at risk,
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$LPL$ is the contribution to the log partial likelihood at time $t$, and
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$\xbar$ and $H$ are the weighted mean and variance of the covariate $x$
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at each time.
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The sum of $H(t)$ over the death times is the second derivative of the
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LPL, also known as the Hessian matrix.
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$U$ is the contribution to the first derivative of the LPL at time $t$
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and $\lambda$ is the increment in the baseline hazard function.
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\section{Test data 1}
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This data set of $n=6$ subjects has a single 0/1 covariate $x$.
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There is one tied death time, one time with both a death and a censored
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observation,
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one with only a death, and one with only censoring.
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(This is as small as a data set can be and still cover these four
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important cases.)
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Let $r = \exp(\beta)$ be the risk score for a subject with $x=1$;
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the risk score is $\exp(0) =1$ for those with $x=0$.
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Table \ref{tab:val1} shows the data set along with the mean and
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increment to the hazard at each time point.
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\begin{table}[b] \centering
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\begin{tabular}{ccc|cc|cc}
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&&& \multicolumn{2}{c|}{$\xbar(t)$} & \multicolumn{2}{c}{$d\lhat_0(t)$} \\
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Time& Status& $x$& Breslow& Efron& Breslow& Efron \\ \hline
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1&1&1&$r/(r+1)$ & $r/(r+1)$& $1/(3r+3)$ & $1/(3r+3)$ \\
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1&0&1&&&&\\
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6&1&1& $r/(r+3)$ & $r/(r+3)$ & $1/(r+3)$& $1/(r+3)$ \\
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6&1&0& $r/(r+3)$ & $r/(r+5)$ & $1/(r+3)$& $1/(r+5)$ \\
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8&0&0&&&& \\
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9&1&0&0&0& 1& 1\\
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\end{tabular}
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\caption{Test data 1}
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\label{tab:val1}
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\end{table}
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\subsection{Breslow estimates}
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\label{sect:valbreslow}
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The log partial likelihood (LPL) has a term for each event; each term is
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the log of the ratio of the score for the subject who had an event over
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the sum of scores for those who did not.
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The LPL, first derivative $U$ of the LPL and
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second derivative (or Hessian) $\imat$ are:
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\begin{eqnarray*}
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LPL &=& \{\beta- \log(3r+3)\} + \{\beta - \log(r+3)\} +
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\{0-\log(r+3)\} + \{0-0\} \\
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&=& 2\beta - \log(3r+3) - 2\log(r+3). \\ \\
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U &=& \left(1-\frac{r}{r+1}\right) + \left(1-\frac{r}{r+3}\right) +
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\left(0-\frac{r}{r+3} \right) + (0-0) \\
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&=& \frac{-r^2 + 3r + 6}{(r+1)(r+3)} .\\ \\
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-\imat&=& \left\{\frac{r}{r+1} - \left( \frac{r}{r+1} \right )^2\right\}
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+2 \left\{\frac{r}{r+3} - \left( \frac{r}{r+3} \right )^2\right\} +
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(0-0) \\
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&=& \frac{r}{(r+1)^2} + \frac{6r}{(r+3)^2}.
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\end{eqnarray*}
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(For a 0/1 covariate the variance formula \eqref{H2} simplifies to
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$\xbar - \xbar^2$, but only in that case. We used this fact above.)
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The actual solution corresponds to $U(\beta)=0$, which from the quadratic
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formula is $r=(1/2)(3 + \sqrt{33})$;
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or $\bhat = \log(r) \approx 1.475285$.
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The following function computes these quantities.
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<<breslow1>>=
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breslow1 <- function(beta) {
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# first test data set, Breslow approximation
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r = exp(beta)
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lpl = 2*beta - (log(3*r +3) + 2*log(r+3))
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U = (6+ 3*r - r^2)/((r+1)*(r+3))
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H = r/(r+1)^2 + 6*r/(r+3)^2
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c(beta=beta, loglik=lpl, U=U, H=H)
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}
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beta <- log((3 + sqrt(33))/2)
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temp <- rbind(breslow1(0), breslow1(beta))
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dimnames(temp)[[1]] <- c("beta=0", "beta=solution")
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temp
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@
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The above call to \code{breslow1} verifies that the first derivative
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is zero at the solution.
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The Newton--Raphson iteration has increments of $-\Cvar U$.
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Starting with the usual initial estimate of $\beta=0$, the first
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iteration is $\beta=8/5$ and further ones are shown below.
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<<>>=
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iter <- matrix(0, nrow=6, ncol=4,
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dimnames=list(paste("iter", 0:5),
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c("beta", "loglik", "U", "H")))
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# Exact Newton-Raphson
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beta <- 0
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for (i in 1:5) {
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iter[i,] <- breslow1(beta)
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beta <- beta + iter[i,"U"]/iter[i,"H"]
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}
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print(iter, digits=9)
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# coxph fits
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test1 <- data.frame(time= c(1, 1, 6, 6, 8, 9),
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status=c(1, 0, 1, 1, 0, 1),
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x= c(1, 1, 1, 0, 0, 0))
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temp <- matrix(0, nrow=6, ncol=4,
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dimnames=list(1:6, c("iter", "beta", "loglik", "H")))
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for (i in 0:5) {
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tfit <- coxph(Surv(time, status) ~ x, data=test1,
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ties="breslow", iter.max=i)
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temp[i+1,] <- c(tfit$iter, coef(tfit), tfit$loglik[2], 1/vcov(tfit))
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}
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temp
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@
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The \code{coxph} routine declares convergence after 4 iterations for this
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data set, so the last two calls with \code{iter.max} of 4 and 5 give
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identical results.
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The martingale residuals are defined as $O-E$ = observed - expected, where
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the observed is the number of events for the subject (0 or 1) and
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$E$ is the expected number assuming that the model is
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completely correct.
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For the first death all 6 subjects are at risk,
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and the martingale formulation views the outcome as a lottery in which
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the subjects hold $r$, $r$, $r$, 1, 1 and 1 tickets, respectively.
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The contribution to $E$ for subject 1 at time 1 is thus $r/(r+3)$.
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Carrying this forward the residuals can be written as simple function of the
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cumulative baseline hazard $\Lambda_0(t)$, the Nelson
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cumulative hazard estimator with case weights of $w_ir_i$; this is
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shown in the `Breslow' column of table \ref{tab:val1}.
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(Also known as the Aalen estimate, Breslow estimate, and all possible
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combinations of the three names.)
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Then the residual can be written as
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\begin{equation}
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M_i = \delta_i - \exp(x_i\beta)\lhat(t_i) \label{mart}
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\end{equation}
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Each of the two subjects who die at time 6 are credited with the full
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hazard increment at time 6.
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Residuals at $\beta=0$ and $\bhat$ are shown in the table below.
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<<mresid1, echo=FALSE>>=
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mresid1 <- function(r) {
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status <- c(1,0,1,1,0,1)
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xbeta <- c(r,r,r,1,1,1)
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temp1 <- 1/(3*r +3)
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temp2 <- 2/(r+3) + temp1
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status - xbeta*c(temp1, temp1, temp2, temp2, temp2, 1+ temp2)
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}
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r0 <- mresid1(1)
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r1 <- round(mresid1((3 + sqrt(33))/2), 6)
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@
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\begin{center}
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\begin{tabular}{c|lrr}
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Subject &\multicolumn{1}{c}{$\Lambda_0$} & $\Mhat(0)$ & $\Mhat(\bhat)$ \\
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\hline
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1& $1/(3r+3)$ & $5/6$ & \Sexpr{r1[1]} \\
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2& $1/(3r+3)$ & $-1/6$ & \Sexpr{r1[2]} \\
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3& $1/(3r+3) + 2/(r+3)$ &$1/3$ & \Sexpr{r1[3]} \\
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4& $1/(3r+3) + 2/(r+3)$ &$1/3$ & \Sexpr{r1[4]} \\
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5& $1/(3r+3) + 2/(r+3)$ & $-2/3$ & \Sexpr{r1[5]} \\
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6 & $1/(3r+3) + 2/(r+3) +1$ & $-2/3$ & \Sexpr{r1[6]}
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\end{tabular}
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\end{center}
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The score statistic $U$ can be written as a two way sum
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involving the covariate(s) and the martingale residuals
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\begin{equation}
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U = \sum_{i=1}^n \int [x_i - \xbar(t)] dM_i(t) \label{score}
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\end{equation}
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The martingale residual $M$ has jumps at the observed
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deaths, leading to the table below with 6 rows and 3 columns.
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The score residuals $L_i$ are defined as the per-patient contributions to
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this total, i.e., the row sums, and the Schoenfeld residuals are the
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per-time point contributions, i.e., the column sums.
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\begin{center}
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\begin{tabular}{cccc}
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&\multicolumn{3}{c}{Time} \\
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Subject & 1 & 6 & 9 \\ \hline
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1&$ \left(1- \frac{r}{r+1} \right) \left(1- \frac{r}{3r+3} \right)$ &0&0 \\
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2& $\left(1- \frac{r}{r+1} \right) \left(0- \frac{r}{3r+3} \right)$ &0&0 \\
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3& $\left(1- \frac{r}{r+1} \right) \left(0- \frac{r}{3r+3} \right)$ &
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$\left(1- \frac{r}{r+3} \right) \left(1- \frac{2r}{r+3} \right)$ & 0\\
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4& $\left(0- \frac{r}{r+1} \right) \left(0- \frac{1}{3r+3} \right)$ &
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$\left(0- \frac{r}{r+3} \right) \left(1- \frac{2}{r+3} \right)$ & 0\\
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5& $\left(0- \frac{r}{r+1} \right) \left(0- \frac{1}{3r+3} \right)$ &
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$\left(0- \frac{r}{r+3} \right) \left(0- \frac{2}{r+3} \right)$ & 0\\
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6& $\left(0- \frac{r}{r+1} \right) \left(0- \frac{1}{3r+3} \right)$ &
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$\left(0- \frac{r}{r+3} \right) \left(0- \frac{2}{r+3} \right)$ &
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(0 - 0) (1-1)
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\end{tabular}
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\end{center}
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At $\beta=0$ the score residuals are 5/12, -1/12, 7/24, -1/24, 5/24 and 5/24.
|
||
|
|
Showing that the three column sums are identical to the three terms of
|
||
|
|
equation \eqref{U1} is left as an exercise for the reader, namely
|
||
|
|
$1- \xbar(1)$, $(1- \xbar(6)) + (0- \xbar(6))$ and $1 - \xbar(9)$.
|
||
|
|
The computer program returns 4 residuals, one per event, rather than one
|
||
|
|
per death time as this has proven to be more useful for plots and other
|
||
|
|
downstream computations.
|
||
|
|
|
||
|
|
In the multivariate case there will be a matrix like the above for each
|
||
|
|
covariate.
|
||
|
|
Let $L$ be the $n$ by $p$ matrix made up of the collection of row sums where
|
||
|
|
$n$ is the number of subjects and $p$ is the number of covariates,
|
||
|
|
this is the matrix of score residuals.
|
||
|
|
The dfbeta residuals are the $n$ by $p$ matrix $D = L \Cvar$; $\imat$ has
|
||
|
|
been defined above for this data set.
|
||
|
|
$D$ is an approximate measure of the influence of each observation on the
|
||
|
|
solution vector.
|
||
|
|
Similarly, the scaled Schoenfeld residuals are the (number of events) by $p$
|
||
|
|
matrix obtained by multiplying the Schoenfeld residuals by $\Cvar$.
|
||
|
|
|
||
|
|
As stated above there is a close connection between the
|
||
|
|
Nelson-Aalen estimate estimate of cumulative hazard and the
|
||
|
|
Breslow approximation for ties.
|
||
|
|
The baseline hazard is shown as the column $\Lambda_0$ in table \ref{tab:val1}.
|
||
|
|
The estimated hazard for a subject with covariate $x_i$ is
|
||
|
|
$\Lambda_i(t) = \exp(x_i \beta) \Lambda_0(t)$ and the survival
|
||
|
|
estimate for the subject is $S_i(t)= \exp(-\Lambda_i(t))$.
|
||
|
|
The variance of the cumulative hazard is the sum of two terms.
|
||
|
|
Term 1 is a natural extension of
|
||
|
|
the Nelson--Aalen estimator to the case where there are
|
||
|
|
weights. It is a running sum, with an increment at each death of
|
||
|
|
$1/(\sum Y_i(t)r_i(t))^2$.
|
||
|
|
For a subject with covariate $x_i$ this term is multiplied by
|
||
|
|
$[\exp(x_i \beta)]^2$.
|
||
|
|
The second term is $c\Cvar c'$, where $\imat$ is the
|
||
|
|
information matrix of the
|
||
|
|
Cox model and $c$ is a vector.
|
||
|
|
The second term accounts for the fact that the
|
||
|
|
weights themselves have a variance;
|
||
|
|
$c$ is the derivative of $S(t)$ with respect to $\beta$
|
||
|
|
and can be formally written as
|
||
|
|
$$ \exp(x\beta) \int_0^t (\bar x(s) - x_i) d\hat\Lambda_0 (s)\,.
|
||
|
|
$$
|
||
|
|
This can be recognized as $-1$ times the score residual process
|
||
|
|
for a subject with $x_i$ as covariates and no events; it measures
|
||
|
|
leverage of a particular observation on the estimate of $\beta$. It is
|
||
|
|
intuitive that a small score residual --- an observation whose
|
||
|
|
covariates has little influence on $\beta$ --- results in a small added
|
||
|
|
variance; that is, $\beta$ has little influence on the estimated survival.
|
||
|
|
|
||
|
|
\begin{center}
|
||
|
|
\begin{tabular}{c|l}
|
||
|
|
Time & Term 1 \\ \hline
|
||
|
|
1& $1/(3r+3)^2$ \\
|
||
|
|
6& $1/(3r+3)^2 + 2/(r+3)^2$ \\
|
||
|
|
9& $1/(3r+3)^2 + 2/(r+3)^2 + 1/1^2$ \\ \multicolumn{2}{c}{} \\
|
||
|
|
Time & $c$ \\ \hline
|
||
|
|
1& $(r/(r+1))* 1/(3r+3)$ \\
|
||
|
|
6& $(r/(r+1))* 1/(3r+3) + (r/(r+3))* 2/(r+3)$ \\
|
||
|
|
9& $(r/(r+1))* 1/(3r+3) + (r/(r+3))* 2/(r+3) + 0*1$\\
|
||
|
|
\end{tabular}
|
||
|
|
\end{center}
|
||
|
|
|
||
|
|
For $\beta=0$, $x=0$:
|
||
|
|
\begin{center}
|
||
|
|
\begin{tabular}{c|lll}
|
||
|
|
Time & \multicolumn{2}{c}{Variance}&\\ \hline
|
||
|
|
1 & 1/36 &+ $1.6*(1/12)^2 $ &= 7/180\\
|
||
|
|
6 & (1/36 + 2/16) &+ $1.6*(1/12 + 2/16)^2 $ &= 2/9\\
|
||
|
|
9 & (1/36 + 2/16 + 1)&+ $1.6*(1/12 + 2/16 + 0)^2$&= 11/9\\
|
||
|
|
\end{tabular}
|
||
|
|
\end{center}
|
||
|
|
|
||
|
|
For $\beta=1.4752849$, $ x=0$
|
||
|
|
\begin{center}
|
||
|
|
\begin{tabular}{c|lll}
|
||
|
|
Time & \multicolumn{2}{c}{Variance}&\\ \hline
|
||
|
|
1 & 0.0038498 &+ .004021 &= 0.007871\\
|
||
|
|
6 & 0.040648 &+ .0704631 &= 0.111111\\
|
||
|
|
9 & 1.040648 &+ .0704631 &= 1.111111\\
|
||
|
|
\end{tabular}
|
||
|
|
\end{center}
|
||
|
|
|
||
|
|
|
||
|
|
\subsection{Efron approximation}
|
||
|
|
The Efron approximation \cite{Efron77}
|
||
|
|
differs from the Breslow only at day 6, where two
|
||
|
|
deaths occur.
|
||
|
|
A useful way to view the approximation is to recast the problem as
|
||
|
|
a lottery model. On day 1 there were 6 subjects in the lottery and
|
||
|
|
1 ticket was drawn, at which time the winner became ineligible for further
|
||
|
|
drawings and withdrew.
|
||
|
|
On day 6 there were 4 subjects in the drawing (at risk)
|
||
|
|
and two tickets (deaths) were drawn.
|
||
|
|
The Breslow approximation considers all four subjects to be eligible for
|
||
|
|
both drawings, which implies that one of them could in theory have won
|
||
|
|
both, that is, died twice. This is of clearly impossible.
|
||
|
|
The Efron approximation treats the two drawings on day 6 as sequential.
|
||
|
|
All four living subjects are at risk for the first of them, then the
|
||
|
|
winner is withdrawn.
|
||
|
|
Three subjects are eligible for the second drawing,
|
||
|
|
either subjects 3, 5, and 6 or subjects 2, 5, and 6, but we
|
||
|
|
do not know which.
|
||
|
|
In some sense then, subjects 3 and 4 each have ``.5 probability" of
|
||
|
|
being at risk for the second event at time 6.
|
||
|
|
In the computation, we treat the two deaths at time 6 as two separate times
|
||
|
|
(two terms
|
||
|
|
in the loglik), with subjects 3 and 4 each having a case weight of 1/2 for the
|
||
|
|
second one.
|
||
|
|
The mean covariate for the second event is then
|
||
|
|
$$
|
||
|
|
\frac{1*r/2 + 0*1/2 + 0*1 + 0*1 }
|
||
|
|
{r/2 + 1/2 + 1+1} = \frac{r}{r+5}
|
||
|
|
$$
|
||
|
|
and the main quantities are
|
||
|
|
\begin{eqnarray*}
|
||
|
|
LL &=& \{\beta- \log(3r+3)\} + \{\beta - \log(r+3)\} + \{0-\log(r/2 +5/2)\}
|
||
|
|
+ \{0-0\} \\
|
||
|
|
&=& 2\beta - \log(3r+3) - \log(r+3) - \log(r/2 +5/2)\\ \\
|
||
|
|
U &=& \left(1-\frac{r}{r+1}\right) + \left(1-\frac{r}{r+3}\right)
|
||
|
|
+ \left(0-\frac{r}{r+5}\right) + (0-0) \\
|
||
|
|
&=& \frac{-r^3 + 23r + 30}{(r+1)(r+3)(r+5)} \\ \\
|
||
|
|
I&=& \left\{\frac{r}{r+1} - \left( \frac{r}{r+1} \right )^2\right\}
|
||
|
|
+ \left\{\frac{r}{r+3} - \left( \frac{r}{r+3} \right )^2\right\} \\
|
||
|
|
&& + \left\{\frac{r}{r+5} - \left( \frac{r}{r+5} \right )^2\right\}.
|
||
|
|
\end{eqnarray*}
|
||
|
|
|
||
|
|
The solution corresponds to the one positive root of $U(\beta)=0$, which is
|
||
|
|
$r=2\sqrt{23/3}\cos(\phi/3)$
|
||
|
|
where $\phi=\arccos\{(45/23)\sqrt{3/23}\}$ via the standard formula
|
||
|
|
for the roots of a cubic equation.
|
||
|
|
This yields $r \approx 5.348721$ or $\bhat = \log(r) \approx 1.676857$.
|
||
|
|
Plugging this value into the formulas above yields
|
||
|
|
\begin{equation*}
|
||
|
|
\begin{array}{ll}
|
||
|
|
LL(0)=-4.276666 & LL(\bhat)=-3.358979 \\
|
||
|
|
U(0) = 52/48 & U(\bhat) = 0 \\
|
||
|
|
\imat(0) = 83/144 & \imat(\bhat) = 0.612632.
|
||
|
|
\end{array}
|
||
|
|
\end{equation*}
|
||
|
|
|
||
|
|
The martingale residuals are again $O-E$, but the expected part of the
|
||
|
|
calculation changes.
|
||
|
|
For the first drawing at time 6 the total number of ``tickets'' in the
|
||
|
|
drawing is $r+1+1+1$; subject 4 has an increment of $r/(r+3)$ and the others
|
||
|
|
$1/(r+3)$ to their expected value.
|
||
|
|
For the second event at time 6 subjects 3 and 4 have a weight of 1/2,
|
||
|
|
the total number of tickets is $(r+5)/2$
|
||
|
|
and the consequent increment in the cumulative hazard is $2/(r+5)$.
|
||
|
|
For $\beta=0$ this calculation is equivalent to the Fleming-Harrington
|
||
|
|
\cite{Fleming84} estimate of cumulative hazard.
|
||
|
|
Subjects 3 and 4 receive 1/2 of this second increment to $E$ and subjects
|
||
|
|
5 and 6 the full increment.
|
||
|
|
Efron \cite{Efron77} did not discuss residuals so did not investigate this
|
||
|
|
aspect of the approximation, we nevertheless sometime refer to
|
||
|
|
this using a label that is some combination of
|
||
|
|
Fleming, Harrington, Efron in the same way as the Nelson-Aalen-Breslow
|
||
|
|
estimate. The martingale residuals are
|
||
|
|
\begin{center}
|
||
|
|
\begin{tabular}{cl}
|
||
|
|
Subject & $M_i$ \\ \hline
|
||
|
|
1 & $1 - r/(3r+3)$ \\
|
||
|
|
2 & $0 - r/(3r+3)$ \\
|
||
|
|
3 & $1 - (r/(3r+3) + r/(r+3) + r/(r+5))$ \\
|
||
|
|
4 & $1 - (1/(3r+3) + 1/(r+3) + 1/(r+5)$ \\
|
||
|
|
5 & $0 - (1/(3r+3) + 1/(r+3) + 2/(r+5)$ \\
|
||
|
|
6 & $1 - (1/(3r+3) + 1/(r+3) + 2/(r+5) + 1)$ \\
|
||
|
|
\end{tabular}
|
||
|
|
\end{center}
|
||
|
|
giving residuals at $\beta=0$ of 5/6, -1/6, 5/12, 5/12, -3/4 and -3/4.
|
||
|
|
|
||
|
|
The matrix defining the score and Schoenfeld residuals
|
||
|
|
has the same first column (time 1) and last column (time 9) as before.
|
||
|
|
At time 6 the hazard increases by $1/(r+3) + 1/(r+5)$, with means of
|
||
|
|
$r/(r+3)$ and $r/(r+5)$.
|
||
|
|
Subjects 5 and 6 each have a contribution of
|
||
|
|
$[0- r/(r+3)][0- 1/(r+3)] + [0- r/(r+5)][0- 1/(r+5)]$ to their score
|
||
|
|
residual; they receive the full increment.
|
||
|
|
The two tied deaths have an increment of
|
||
|
|
\begin{align*}
|
||
|
|
s_3(6) &= 1 - .5\left(\frac{r}{r+3} + \frac{r}{r+5}\right) +
|
||
|
|
\left(1- \frac{r}{r+3}\right)\frac{-1}{r+3} +
|
||
|
|
\left(1- \frac{r}{r+5}\right)\frac{-.5}{r+5} \\
|
||
|
|
s_4(6) &= 0 - .5\left(\frac{r}{r+3} + \frac{r}{r+5}\right) +
|
||
|
|
\left(0- \frac{r}{r+3}\right)\frac{-1}{r+3} +
|
||
|
|
\left(0- \frac{r}{r+5}\right)\frac{-.5}{r+5}
|
||
|
|
\end{align*}
|
||
|
|
We can't as neatly collapse the deaths: the $dN$ and $d\Lambda$ parts of their
|
||
|
|
martigale residual end up as separate terms. The first can be written as
|
||
|
|
$x - \rm{ave}(\xbar)$: if there were $k$ tied deaths the average of the $k$
|
||
|
|
$\xbar$ terms that arise there.
|
||
|
|
For the $d\Lambda$ term they get credit for all of the
|
||
|
|
first hazard jump, $(k-1)/k$ of the second, $(k-2)/k$ of the third, \ldots,
|
||
|
|
$1/k$ of the last.
|
||
|
|
|
||
|
|
|
||
|
|
The contributions
|
||
|
|
for a tied death time with the
|
||
|
|
following contributions at time 6.
|
||
|
|
\begin{center}
|
||
|
|
\begin{tabular}{ccc}
|
||
|
|
&\multicolumn{2}{c}{Time} \\
|
||
|
|
Subject & 6 (first) & 6 (second)\\ \hline
|
||
|
|
1&0 & 0 \\
|
||
|
|
2&0 & 0 \\
|
||
|
|
3& $\left(1- \frac{r}{r+3} \right) \left(1- \frac{r}{r+3} \right)$ &
|
||
|
|
$\left(1- \frac{r}{r+5} \right) \left(1- \frac{2r}{r+5} \right)/2$ \\
|
||
|
|
4& $\left(0- \frac{r}{r+3} \right) \left(0- \frac{1}{r+3} \right)$ &
|
||
|
|
$\left(0- \frac{r}{r+5} \right) \left(1- \frac{2}{r+5} \right)/2$ \\
|
||
|
|
5& $\left(0- \frac{r}{r+3} \right) \left(0- \frac{1}{r+3} \right)$ &
|
||
|
|
$\left(0- \frac{r}{r+5} \right) \left(0- \frac{2}{r+5} \right)$ \\
|
||
|
|
6& $\left(0- \frac{r}{r+3} \right) \left(0- \frac{1}{r+3} \right)$ &
|
||
|
|
$\left(0- \frac{r}{r+5} \right) \left(0- \frac{2}{r+5} \right)$
|
||
|
|
\end{tabular}
|
||
|
|
\end{center}
|
||
|
|
The score residuals at $\beta=0$ are 5/12, -1/12, 55/144, -5/144,
|
||
|
|
29/144 and 29/144.
|
||
|
|
|
||
|
|
It is an error to generate residuals for the Efron method by using
|
||
|
|
formula \eqref{mart}, which was derived from the Breslow approximation.
|
||
|
|
It is clear that some packages
|
||
|
|
do exactly this, however, which can be verified using formulas from above.
|
||
|
|
(Statistical forensics is another use for our results.)
|
||
|
|
What are the consequences of this?
|
||
|
|
On a formal level the resulting ``martingale residuals'' no longer have
|
||
|
|
an expected value of 0 and thus are not martingales,
|
||
|
|
so one loses theoretical backing for derived plots or statistics.
|
||
|
|
The score, Schoenfeld, dfbeta and scaled Schoenfeld residuals are based on
|
||
|
|
the martingale residual so suffer the same loss.
|
||
|
|
On a practical level, when the fraction of ties is small it is quite often the
|
||
|
|
case that $\bhat$ is nearly the same when using the Breslow and Efron
|
||
|
|
approach. We have normally found the correct and ad hoc residuals to
|
||
|
|
be similar as well in that case, sufficiently so that
|
||
|
|
explorations of functional form (martingale residuals), leverage and robust
|
||
|
|
variance (dfbeta) and proportional hazards (scaled Schoenfeld) led to
|
||
|
|
the same conclusions.
|
||
|
|
This may not hold when there is a large number of ties.
|
||
|
|
|
||
|
|
The variance formula for the baseline hazard function in the Efron case
|
||
|
|
is evaluated the same way as before, as
|
||
|
|
the sum of $(\mbox{hazard increment})^2$,
|
||
|
|
treating a tied death as multiple separate
|
||
|
|
hazard increments.
|
||
|
|
In term 1 of the variance, the variance increment at time 6 is
|
||
|
|
now $1/(r+3)^2 + 4/(r+5)^2$ rather than $2/(r+3)^2$.
|
||
|
|
The increment to $d$ at time 6 is
|
||
|
|
$(r/(r+3))* 1/(r+3) + (r/(r+5))* 2/(r+5)$.
|
||
|
|
(Numerically, the result of this
|
||
|
|
computation is intermediate between the
|
||
|
|
Nelson--Aalen variance and the
|
||
|
|
Greenwood variance used in the Kaplan--Meier.)
|
||
|
|
|
||
|
|
For $\beta=0$, $x=0$, let $v= \Cvar = 144/83$.
|
||
|
|
\begin{center}
|
||
|
|
\begin{tabular}{c|ll}
|
||
|
|
Time & \multicolumn{2}{c}{Variance}\\ \hline
|
||
|
|
1 & 1/36 \\ &
|
||
|
|
\quad + $v(1/12)^2 $ &= \phantom{0}119/2988\\
|
||
|
|
6 & (1/36 + 1/16 + 4/25)& \\
|
||
|
|
&\quad + $v(1/12 + 1/16+ 1/18)^2$ &= 1996/6225\\
|
||
|
|
9 & (1/36 + 1/16 + 4/25 + 1) \\&
|
||
|
|
\quad + $v(1/12 + 1/16 + 1/18 +0)^2$&= 8221/6225\\
|
||
|
|
\end{tabular}
|
||
|
|
\end{center}
|
||
|
|
|
||
|
|
For $\beta=1.676857$, $ x=0$.
|
||
|
|
\begin{center}
|
||
|
|
\begin{tabular}{c|ll}
|
||
|
|
Time & \multicolumn{2}{c}{Variance}\\ \hline
|
||
|
|
1 & 0.00275667 + .00319386 & = 0.0059505\\
|
||
|
|
6 & 0.05445330 + .0796212 & = 0.134075\\
|
||
|
|
9 & 1.05445330 + .0796212 &= 1.134075\\
|
||
|
|
\end{tabular}
|
||
|
|
\end{center}
|
||
|
|
|
||
|
|
\subsection{Exact partial likelihood}
|
||
|
|
Returning to the lottery analogy, for the two deaths at time 6
|
||
|
|
the exact partial likelihood computes the direct probability that
|
||
|
|
those two subjects would be selected given that a pair will be chosen.
|
||
|
|
The numerator is $r_3 r_4$, the product of the risk scores of the subjects
|
||
|
|
with an event, and the denominator is the sum over all 6 pairs
|
||
|
|
who could have been chosen: $r_3r_4 + r_3r_5 + r_3r_6 + r_4 r_5 + r_4r_6
|
||
|
|
+ r_5r_6$.
|
||
|
|
(If there were 10 tied deaths from a pool of 60 available the
|
||
|
|
sum will have over 75 billion terms, each a product of 10 values;
|
||
|
|
a truly formidable computation!)
|
||
|
|
In our case, three of the four subjects at risk at time 6 have a risk score
|
||
|
|
of $\exp(0x)=1$ and one a risk score of $r$,
|
||
|
|
and the denominator is $r +r+ r+1 +1 +1$.
|
||
|
|
\begin{eqnarray*}
|
||
|
|
LL &=& \{\beta- \log(3r+3)\} + \{\beta - \log(3r+3)\} + \{0-0\} \\
|
||
|
|
&=& 2\{\beta - \log(3r+3)\}. \\ \\
|
||
|
|
U &=& \left(1-\frac{r}{r+1}\right) + \left(1-\frac{r}{r+1}\right) + (0-0)\\
|
||
|
|
&=& \frac{2}{r+1}. \\ \\
|
||
|
|
-\imat&=& \frac{2r}{(r+1)^2}. \\
|
||
|
|
\end{eqnarray*}
|
||
|
|
|
||
|
|
The solution $U(\beta)=0$ corresponds to $r=\infty$, with a loglikelihood
|
||
|
|
that asymptotes to $-2\log(3)$ = 2.1972.
|
||
|
|
The Newton--Raphson iteration has increments of $(r+1)/r$ leading to
|
||
|
|
the following iteration for $\bhat$:
|
||
|
|
<<iter>>=
|
||
|
|
temp <- matrix(0, 8, 3)
|
||
|
|
dimnames(temp) <- list(paste0("iteration ", 0:7, ':'), c("beta", "loglik", "H"))
|
||
|
|
bhat <- 0
|
||
|
|
for (i in 1:8) {
|
||
|
|
r <- exp(bhat)
|
||
|
|
temp[i,] <- c(bhat, 2*(bhat - log(3*r +3)), 2*r/(r+1)^2)
|
||
|
|
bhat <- bhat + (r+1)/r
|
||
|
|
}
|
||
|
|
round(temp,3)
|
||
|
|
@
|
||
|
|
The Newton-Raphson iteration quickly settles down to addition of a constant
|
||
|
|
increment to $\bhat$ at each step
|
||
|
|
while the partial likelihood approaches an asymptote:
|
||
|
|
this is a fairly common case when the Cox MLE is infinite.
|
||
|
|
A solution at $\bhat=10$ or 15 is hardly different in likelihood from the
|
||
|
|
true maximum, and most programs will stop iterating around this point.
|
||
|
|
The information matrix, which measures the curvature of the likelihood
|
||
|
|
function at $\beta$, rapidly goes to zero as $\beta$ grows.
|
||
|
|
|
||
|
|
It is difficult to describe a satisfactory definition of the expected number
|
||
|
|
of events for each subject and thus a definition of the proper
|
||
|
|
martingale residual for the exact calculation.
|
||
|
|
Among other things it should lead to a consistent score residual,
|
||
|
|
i.e., ones that sum to the total score statistic $U$
|
||
|
|
\begin{align*}
|
||
|
|
L_i &= \int (x_i - \xbar(t)) dM_i(t) \\
|
||
|
|
\sum L_i &= U
|
||
|
|
\end{align*}
|
||
|
|
The residuals defined above for the Breslow and Efron approximations have this property,
|
||
|
|
for instance.
|
||
|
|
The exact partial likelihood contribution to $U$ for a set of set of $k$
|
||
|
|
tied deaths, however, is a sum of all subsets of size $k$; how would one
|
||
|
|
partition this term as a simple sum over subjects?
|
||
|
|
|
||
|
|
The exact partial likelihood is infrequently used and examination of
|
||
|
|
post fit residuals is even rarer.
|
||
|
|
The survival package (and all others that I know of) takes the easy
|
||
|
|
road in this case and uses equation \eqref{mart} along with the
|
||
|
|
Nelson-Aalen-Breslow hazard to form residuals.
|
||
|
|
They are certainly not correct, but the viable options were to use
|
||
|
|
this, the Efron residuals, or print an error message.
|
||
|
|
|
||
|
|
At $\bhat=\infty$ the Breslow residuals are still well defined.
|
||
|
|
Subjects 1 to 3, those with a covariate of 1, experience a hazard of
|
||
|
|
$r/(3r+3)=1/3$ at time 1. Subject 3 accumulates a hazard of 1/3 at
|
||
|
|
time 1 and a further hazard of 2 at time 6.
|
||
|
|
The remaining subjects are at an infinitely lower risk during days
|
||
|
|
1 to 6 and accumulate no hazard then, with subject 6 being credited with
|
||
|
|
1 unit of hazard at the last event.
|
||
|
|
The residuals are thus $1-1/3=2/3$, $0-1/3$, $1-7/3= -4/3$, $1-0$, 0, and 0,
|
||
|
|
respectively, for the six subjects.
|
||
|
|
|
||
|
|
\section{Test data 2}
|
||
|
|
This data set also has a single covariate, but in this case
|
||
|
|
a (start, stop] style of input is employed.
|
||
|
|
Table \ref{tab:val2} shows the data sorted by the end time of the risk
|
||
|
|
intervals. The columns for $\xbar$ and hazard are the values
|
||
|
|
at the event times; events occur at the end of
|
||
|
|
each interval for which status = 1.
|
||
|
|
\begin{table}\centering
|
||
|
|
\begin{tabular}{ccc|ccc}
|
||
|
|
&&&Number& \\
|
||
|
|
Time&Status&$x$&at Risk& $\xbar$& $d\lhat$ \\ \hline
|
||
|
|
(1,2] &1 &1 &2 &$r/(r+1)$ & $1/(r+1)$\\
|
||
|
|
(2,3] &1 &0 &3 & $r/(r+2)$ & $1/(r+2)$ \\
|
||
|
|
(5,6] &1 &0 &5 & $3r/(3r+2)$ & $1/(3r+2)$ \\
|
||
|
|
(2,7] &1 &1 &4 & $3r/(3r+1)$ & $1/(3r+1)$ \\
|
||
|
|
(1,8] &1 &0 &4 & $3r/(3r+1)$ & $1/(3r+1)$ \\
|
||
|
|
(7,9] &1 &1 &5 & $3r/(3r+2)$ & $2/(3r+2)$ \\
|
||
|
|
(3,9] &1 &1 && \\
|
||
|
|
(4,9] &0 &1 && \\
|
||
|
|
(8,14]&0 &0 &2& 0&0 \\
|
||
|
|
(8,17]&0 &0 &1& 0&0 \\
|
||
|
|
\end{tabular}
|
||
|
|
\caption{Test data 2}
|
||
|
|
\label{tab:val2}
|
||
|
|
\end{table}
|
||
|
|
|
||
|
|
\subsection{Breslow approximation}
|
||
|
|
For the Breslow approximation we have
|
||
|
|
\begin{eqnarray*}
|
||
|
|
LL &=& \log\left(\frac{r}{r+1}\right)
|
||
|
|
+\log\left(\frac{1}{r+2}\right)
|
||
|
|
+\log\left(\frac{1}{3r+2}\right) +\\
|
||
|
|
&& \log\left(\frac{r}{3r+1}\right)
|
||
|
|
+\log\left(\frac{1}{3r+1}\right)
|
||
|
|
+2\log\left(\frac{r}{3r+2}\right) \\
|
||
|
|
&=& 4\beta - \log(r+1) - \log(r+3)- 3\log(3r+2) -2\log(3r+1). \\ \\
|
||
|
|
U &=& \left(1-\frac{r}{r+1}\right) + \left(0-\frac{r}{r+2}\right)
|
||
|
|
+ \left(0-\frac{3r}{3r+2}\right) + \\
|
||
|
|
&& \left(1-\frac{3r}{3r+1}\right) +
|
||
|
|
\left(0-\frac{3r}{3r+1}\right) +
|
||
|
|
2\left(1-\frac{3r}{3r+2}\right) \\
|
||
|
|
\\ \\
|
||
|
|
\imat &=& \frac{r}{(r+1)^2} + \frac{2r}{(r+2)^2} +
|
||
|
|
\frac{6r}{(3r+2)^2} + \frac{3r}{(3r+1)^2} \\
|
||
|
|
&& \frac{3r}{(3r+1)^2} + \frac{12r}{(3r+2)^2} . \\
|
||
|
|
\end{eqnarray*}
|
||
|
|
|
||
|
|
In this case $U$ is a quartic equation
|
||
|
|
and we find the solution numerically.
|
||
|
|
<<breslow2>>=
|
||
|
|
ufun <- function(r) {
|
||
|
|
4 - (r/(r+1) + r/(r+2) + 3*r/(3*r+2) + 6*r/(3*r+1) + 6*r/(3*r+2))
|
||
|
|
}
|
||
|
|
rhat <- uniroot(ufun, c(.5, 1.5), tol=1e-8)$root
|
||
|
|
bhat <- log(rhat)
|
||
|
|
c(rhat=rhat, bhat=bhat)
|
||
|
|
@
|
||
|
|
The solution is at $U(\bhat)=0$ or $r \approx .9189477$;
|
||
|
|
$\bhat = \log(r) \approx -.084526$.
|
||
|
|
Then
|
||
|
|
<<temp, echo=FALSE>>=
|
||
|
|
true2 <- function(beta, newx=0) {
|
||
|
|
r <- exp(beta)
|
||
|
|
loglik <- 4*beta - log(r+1) - log(r+2) - 3*log(3*r+2) - 2*log(3*r+1)
|
||
|
|
u <- 1/(r+1) + 1/(3*r+1) + 4/(3*r+2) -
|
||
|
|
( r/(r+2) +3*r/(3*r+2) + 3*r/(3*r+1))
|
||
|
|
imat <- r/(r+1)^2 + 2*r/(r+2)^2 + 6*r/(3*r+2)^2 +
|
||
|
|
3*r/(3*r+1)^2 + 3*r/(3*r+1)^2 + 12*r/(3*r+2)^2
|
||
|
|
|
||
|
|
hazard <-c( 1/(r+1), 1/(r+2), 1/(3*r+2), 1/(3*r+1), 1/(3*r+1), 2/(3*r+2) )
|
||
|
|
xbar <- c(r/(r+1), r/(r+2), 3*r/(3*r+2), 3*r/(3*r+1), 3*r/(3*r+1),
|
||
|
|
3*r/(3*r+2))
|
||
|
|
# The matrix of weights, one row per obs, one col per time
|
||
|
|
# deaths at 2,3,6,7,8,9
|
||
|
|
wtmat <- matrix(c(1,0,0,0,1,0,0,0,0,0,
|
||
|
|
0,1,0,1,1,0,0,0,0,0,
|
||
|
|
0,0,1,1,1,0,1,1,0,0,
|
||
|
|
0,0,0,1,1,0,1,1,0,0,
|
||
|
|
0,0,0,0,1,1,1,1,0,0,
|
||
|
|
0,0,0,0,0,1,1,1,1,1), ncol=6)
|
||
|
|
wtmat <- diag(c(r,1,1,r,1,r,r,r,1,1)) %*% wtmat
|
||
|
|
|
||
|
|
x <- c(1,0,0,1,0,1,1,1,0,0)
|
||
|
|
status <- c(1,1,1,1,1,1,1,0,0,0)
|
||
|
|
xbar <- colSums(wtmat*x)/ colSums(wtmat)
|
||
|
|
n <- length(x)
|
||
|
|
|
||
|
|
# Table of sums for score and Schoenfeld resids
|
||
|
|
hazmat <- wtmat %*% diag(hazard) #each subject's hazard over time
|
||
|
|
dM <- -hazmat #Expected part
|
||
|
|
for (i in 1:6) dM[i,i] <- dM[i,i] +1 #observed
|
||
|
|
dM[7,6] <- dM[7,6] +1 # observed
|
||
|
|
mart <- rowSums(dM)
|
||
|
|
|
||
|
|
# Table of sums for score and Schoenfeld resids
|
||
|
|
# Looks like the last table of appendix E.2.1 of the book
|
||
|
|
resid <- dM * outer(x, xbar, '-')
|
||
|
|
score <- rowSums(resid)
|
||
|
|
scho <- colSums(resid)
|
||
|
|
# We need to split the two tied times up, to match coxph
|
||
|
|
scho <- c(scho[1:5], scho[6]/2, scho[6]/2)
|
||
|
|
var.g <- cumsum(hazard*hazard /c(1,1,1,1,1,2))
|
||
|
|
var.d <- cumsum( (xbar-newx)*hazard)
|
||
|
|
|
||
|
|
surv <- exp(-cumsum(hazard) * exp(beta*newx))
|
||
|
|
varhaz <- (var.g + var.d^2/imat)* exp(2*beta*newx)
|
||
|
|
|
||
|
|
list(loglik=loglik, u=u, imat=imat, xbar=xbar, haz=hazard,
|
||
|
|
mart=mart, score=score, rmat=resid,
|
||
|
|
scho=scho, surv=surv, var=varhaz)
|
||
|
|
}
|
||
|
|
val2 <- true2(bhat)
|
||
|
|
rtemp <- round(val2$mart, 6)
|
||
|
|
@
|
||
|
|
$$
|
||
|
|
\begin{array}{ll}
|
||
|
|
LL(0)= \Sexpr{round(true2(0)$loglik, 6)} &
|
||
|
|
LL(\bhat)= \Sexpr{round(val2$loglik,6)} \\
|
||
|
|
U(0) = -2/15 & U(\bhat) = 0 \\
|
||
|
|
\imat(0) = 2821/1800 & \imat(\bhat) = \Sexpr{round(val2$imat,6)} %$
|
||
|
|
\end{array}
|
||
|
|
$$
|
||
|
|
|
||
|
|
\def\haz{\hat \lambda}
|
||
|
|
The martingale residuals are (status--cumulative hazard)
|
||
|
|
or $O-E = \delta_i - \int Y_i(s) r_i d\lhat(s)$.
|
||
|
|
Let $\haz_1, \ldots, \haz_6$ be the six increments to the cumulative
|
||
|
|
hazard listed in Table \ref{tab:val2}. Then the cumulative hazards and
|
||
|
|
martingale residuals for the subjects are as follows.
|
||
|
|
\begin{center}
|
||
|
|
\begin{tabular}{c|lrr}
|
||
|
|
Subject &$\Lambda_i$ & $\Mhat(0)$ & $\Mhat(\bhat)$ \\ \hline
|
||
|
|
1& $r\haz_1$ & 1--30/60 & \Sexpr{rtemp[1]} \\
|
||
|
|
2& $\haz_2 $ & 1--20/60 & \Sexpr{rtemp[2]}\\
|
||
|
|
3& $\haz_3 $ & 1--12/60 & \Sexpr{rtemp[3]} \\
|
||
|
|
4& $r(\haz_2 + \haz_3 + \haz_4)$& 1--47/60 & \Sexpr{rtemp[4]}\\
|
||
|
|
5& $\haz_1+\haz_2+\haz_3+\haz_4+\haz_5$& 1--92/60 & \Sexpr{rtemp[5]}\\
|
||
|
|
6 &$r*(\haz_5 + \haz_6) $& 1--39/60 & \Sexpr{rtemp[6]} \\
|
||
|
|
7& $r*(\haz_3+\haz_4+\haz_5+ \haz_6)$& 1--66/60& \Sexpr{rtemp[7]}\\
|
||
|
|
8& $r*(\haz_3+\haz_4+\haz_5+ \haz_6)$& 0--66/60&\Sexpr{rtemp[8]} \\
|
||
|
|
9& $\haz_6$ & 0--24/60 & \Sexpr{rtemp[9]} \\
|
||
|
|
10& $\haz_6$ & 0--24/60 & \Sexpr{rtemp[10]}
|
||
|
|
\end{tabular}
|
||
|
|
\end{center}
|
||
|
|
|
||
|
|
The score and Schoenfeld residuals can be laid out in a tabular fashion.
|
||
|
|
Each entry in the table is the value of $\{x_i - \xbar(t_j)\} d\Mhat_i(t_j)$
|
||
|
|
for subject $i$ and event time $t_j$.
|
||
|
|
The row sums of the table are the score residuals for the subject;
|
||
|
|
the column sums are the Schoenfeld residuals at each event time.
|
||
|
|
Below is the table for $\beta= \log(2)$ ($r=2$).
|
||
|
|
This is a slightly more stringent test than the table for $\beta=0$,
|
||
|
|
since in this latter case a program could be missing a factor of
|
||
|
|
$r = \exp(\beta)=1$ and give the correct answer.
|
||
|
|
However, the results are much more compact than those for $\bhat$,
|
||
|
|
since the solutions are exact fractions.
|
||
|
|
|
||
|
|
%\newcommand{\pf}[2]{$\left(\frac{#1}{#2}\right)$} %positive fraction
|
||
|
|
%\newcommand{\nf}[2]{$\left(\frac{-#1}{#2}\right)$} %negative fraction
|
||
|
|
\newcommand{\pf}[2]{$\phantom{-}\frac{#1}{#2}$} %positive fraction
|
||
|
|
\newcommand{\nf}[2]{$-\frac{#1}{#2}$} %negative fraction
|
||
|
|
\renewcommand{\arraystretch}{1.5}
|
||
|
|
|
||
|
|
\begin{center}
|
||
|
|
\begin{tabular}{c|cccccc|c}
|
||
|
|
& \multicolumn{6}{c|}{Event Time} & Score\\
|
||
|
|
Id&2&3&6&7&8&9& Resid \\ \hline
|
||
|
|
1&\pf{1}{9} &&&&&& $\phantom{-}\frac{1}{9}$ \\
|
||
|
|
2&&\nf{3}{8} &&&&& $-\frac{3}{8}$ \\
|
||
|
|
3&&&\nf{21}{32}&&&& $-\frac{21}{32}$ \\
|
||
|
|
4&&\nf{1}{4} & \nf{1}{16} & \pf{5}{49} &&&
|
||
|
|
$-\frac{165}{784} $\\
|
||
|
|
5&\pf{2}{9}& \pf{1}{8} & \pf{3}{32} &
|
||
|
|
\pf{6}{49} & \nf{36}{49}&&
|
||
|
|
$-\frac{2417}{14112} $\\
|
||
|
|
6&&&&& \nf{2}{49} & \pf{1}{8} &
|
||
|
|
$\phantom{-}\frac{33}{392}$ \\
|
||
|
|
7&&& \nf{1}{16} & \nf{2}{49}& \nf{2}{49} &
|
||
|
|
\pf{1}{8} & $-\frac{15}{784}$ \\
|
||
|
|
8&&& \nf{1}{16} & \nf{2}{49}& \nf{2}{49} &
|
||
|
|
\nf{1}{8} & $-\frac{211}{784}$ \\
|
||
|
|
9&&&&&& \pf{3}{16} &$ \phantom{-}\frac{3}{16}$ \\
|
||
|
|
10&&&&&& \pf{3}{16} & $\phantom{-}\frac{3}{16}$ \\ \hline
|
||
|
|
& \pf{1}{3} &\nf{1}{2} & \nf{3}{4} &
|
||
|
|
\pf{1}{7} & \nf{6}{7} & \pf{1}{2} & \nf{95}{84} \\
|
||
|
|
|
||
|
|
&&&&&&& \\
|
||
|
|
& $\frac{1}{r+1}$ & $\frac{-r}{r+2}$ & $\frac{-3r}{r+2}$ & $\frac{1}{3r+1}$ &
|
||
|
|
$\frac{3r}{3r+1}$ & $\frac{4}{3r+2}$
|
||
|
|
\end{tabular}
|
||
|
|
\end{center}
|
||
|
|
Both the Schoenfeld and score residuals sum to the score statistic $U(\beta)$.
|
||
|
|
As discussed further above, programs will return two Schoenfeld residuals
|
||
|
|
at time 9, one for each subject who had an event at that time.
|
||
|
|
|
||
|
|
\subsection{Efron approximation}
|
||
|
|
This example has only one tied death time, so only the term(s) for the
|
||
|
|
event at time 9 change. The main quantities at that time point are as follows.
|
||
|
|
\begin{center}
|
||
|
|
\begin{tabular}{r|cc}
|
||
|
|
&Breslow & Efron \\ \hline
|
||
|
|
$LL$ & $2\log\left(\frac{r}{3r+2}\right)$ &
|
||
|
|
$\log\left(\frac{r}{3r+2}\right) + \log\left(\frac{r}{2r+2}\right)$ \\
|
||
|
|
$U$ & $\frac{2}{3r+2}$& $\frac{1}{3r+2} + \frac{1}{2r+2}$ \\
|
||
|
|
$\imat$& $2\frac{6r}{(3r+2)^2} $ &$\frac{6r}{(3r+2)^2} + \frac{4r}{(2r+2)^2}$\\
|
||
|
|
$d\lhat$ & $\frac{2}{3r+2} $ & $\frac{1}{3r+2} + \frac{1}{2r+2}$
|
||
|
|
\end{tabular}
|
||
|
|
\end{center}
|
||
|
|
\renewcommand{\arraystretch}{1}
|
||
|
|
|
||
|
|
|
||
|
|
\section{Test data 3}
|
||
|
|
This is very similar to test data 1, but with the addition of case
|
||
|
|
weights.
|
||
|
|
There are 9 observations, $x$ is a 0/1/2 covariate, and weights range from
|
||
|
|
1 to 4.
|
||
|
|
As before, let $r = \exp(\beta)$ be the risk score for a subject with $x=1$.
|
||
|
|
Table \ref{tab:val3} shows the data set along with the mean and
|
||
|
|
increment to the hazard at each point.
|
||
|
|
|
||
|
|
\begin{table} \centering
|
||
|
|
\begin{tabular}{cccc|cc}
|
||
|
|
Time&Status&$X$ & Wt& $\xbar(t)$ & $d\lhat_0(t)$ \\ \hline
|
||
|
|
1& 1& 2 & 1& $(2r^2+11r) d\lhat_0 =\xbar_1$ & $1/(r^2 + 11r +7)$ \\
|
||
|
|
1& 0& 0 & 2&& \\
|
||
|
|
2& 1& 1 & 3& $11r/(11r+5) = \xbar_2$ & $10/(11r+5)$ \\
|
||
|
|
2& 1& 1 & 4&& \\
|
||
|
|
2& 1& 0 & 3&& \\
|
||
|
|
2& 0& 1 & 2&& \\
|
||
|
|
3& 0& 0 & 1&& \\
|
||
|
|
4& 1& 1 & 2& $2r/(2r+1)= \xbar_3$ & $ 2/(2r+1)$ \\
|
||
|
|
5& 0& 0 & 1 & \\
|
||
|
|
\end{tabular}
|
||
|
|
\caption{Test data 3}
|
||
|
|
\label{tab:val3}
|
||
|
|
\end{table}
|
||
|
|
|
||
|
|
\subsection{Breslow estimates}
|
||
|
|
The likelihood is a product of terms, one for each death, of
|
||
|
|
the form
|
||
|
|
$$
|
||
|
|
\left( \frac{e^{X_i \beta}}{\sum_j Y_j(t_i) w_j e^{X_j \beta}}
|
||
|
|
\right) ^{w_i}
|
||
|
|
$$
|
||
|
|
For integer weights, this gives the same results as would
|
||
|
|
be obtained by replicating each observation the specified number of times,
|
||
|
|
which is in fact one motivation for the definition.
|
||
|
|
The definitions for the score vector $U$ and information matrix $\imat$
|
||
|
|
simply replace the mean and variance with weighted versions of the same.
|
||
|
|
Let $PL(\beta,w)$ be the log partial liklihood when all the observations
|
||
|
|
are given
|
||
|
|
a common case weight of $w$;
|
||
|
|
it is easy to prove that $PL(\beta,w) = wPL(\beta,1) - d\log(w)$ where $d$ is
|
||
|
|
the number of events.
|
||
|
|
One consequence of this is that $PL$ can be positive for weights
|
||
|
|
that are less than 1, a case which
|
||
|
|
sometimes occurs in survey sampling applications. (This can be a big
|
||
|
|
surprise the first time one encounters it.)
|
||
|
|
\begin{eqnarray*}
|
||
|
|
LL &=& \{2\beta - \log(r^2 + 11r +7)\} + 3\{\beta - \log(11r+5)\} \\
|
||
|
|
&& + 4\{\beta - \log(11r+5)\} +3\{0 - \log(11r+5)\} \\
|
||
|
|
&& + 2\{\beta - \log(2r+1) \} \\
|
||
|
|
&=& 11\beta - \log(r^2 + 11r +7) -10\log(11r+5) - 2\log(2r+1) \\\\
|
||
|
|
U &=& (2- \xbar_1) + 3(0-\xbar_2) + 4(1-\xbar_2) + 3(1-\xbar_2) +
|
||
|
|
2(1-\xbar_3) \\
|
||
|
|
&=& 11 - [(2r^2+11r)/(r^2+11r+7) + 10(11r/(11r+5)) + 2(2r/(2r+1))] \\
|
||
|
|
I &=& [(4r^2 + 11r)/(r^2 + 11r +7) - \xbar_1^2] + 10(\xbar_2 - \xbar_2^2)
|
||
|
|
+ 2(\xbar_3 - \xbar_3^2) \\
|
||
|
|
\end{eqnarray*}
|
||
|
|
|
||
|
|
The solution corresponds to $U(\beta)=0$ and can be computed using a
|
||
|
|
simple search for the zero of the equation.
|
||
|
|
<<wt1>>=
|
||
|
|
ufun <- function(r) {
|
||
|
|
xbar <- c( (2*r^2 + 11*r)/(r^2 + 11*r +7), 11*r/(11*r + 5), 2*r/(2*r +1))
|
||
|
|
11- (xbar[1] + 10* xbar[2] + 2* xbar[3])
|
||
|
|
}
|
||
|
|
rhat <- uniroot(ufun, c(1,3), tol= 1e-9)$root
|
||
|
|
bhat <- log(rhat)
|
||
|
|
c(rhat=rhat, bhat=bhat)
|
||
|
|
@
|
||
|
|
From this we have
|
||
|
|
<<wt2>>=
|
||
|
|
wfun <- function(r) {
|
||
|
|
beta <- log(r)
|
||
|
|
pl <- 11*beta - (log(r^2 + 11*r + 7) + 10*log(11*r +5) + 2*log(2*r +1))
|
||
|
|
xbar <- c((2*r^2 + 11*r)/(r^2 + 11*r +7), 11*r/(11*r +5), 2*r/(2*r +1))
|
||
|
|
U <- 11 - (xbar[1] + 10*xbar[2] + 2*xbar[3])
|
||
|
|
H <- ((4*r^2 + 11*r)/(r^2 + 11*r +7)- xbar[1]^2) +
|
||
|
|
10*(xbar[2] - xbar[2]^2) + 2*(xbar[3]- xbar[3]^2)
|
||
|
|
c(loglik=pl, U=U, H=H)
|
||
|
|
}
|
||
|
|
temp <- matrix(c(wfun(1), wfun(rhat)), ncol=2,
|
||
|
|
dimnames=list(c("loglik", "U", "H"), c("beta=0", "beta-hat")))
|
||
|
|
round(temp, 6)
|
||
|
|
@
|
||
|
|
|
||
|
|
When $\beta=0$, the three unique values for $\xbar$
|
||
|
|
at $t=1$, 2, and 4
|
||
|
|
are 13/19, 11/16 and 2/3,
|
||
|
|
respectively, and the increments to the cumulative hazard are
|
||
|
|
1/19, 10/16 = 5/8, and 2/3, see table \ref{tab:val3}.
|
||
|
|
The martingale and score residuals at $\beta=0$ and
|
||
|
|
$\bhat$ are
|
||
|
|
\begin{center}
|
||
|
|
\begin{tabular}{cc|lr}
|
||
|
|
Id &Time& \multicolumn{1}{c}{$M(0)$} &\multicolumn{1}{c}{$M(\bhat)$} \\ \hline
|
||
|
|
A&1 & $1-1/19 = 18/19 $&0.85531\\
|
||
|
|
B&1 & $0-1/19 = -1/19 $&-0.02593\\
|
||
|
|
C&2 & $1-(1/19 + 5/8)= 49/152 $&0.17636 \\
|
||
|
|
D&2 & $1-(1/19 + 5/8)= 49/152 $&0.17636\\
|
||
|
|
E&2 & $1-(1/19 + 5/8)= 49/152 $&0.65131\\
|
||
|
|
F&2 & $0-(1/19 + 5/8)= -103/152 $&-0.82364\\
|
||
|
|
G&3 & $0-(1/19 + 5/8)= -103/152 $&-0.34869\\
|
||
|
|
H&4 & $1-(1/19 + 5/8 +2/3)= -157/456 $&-0.64894\\
|
||
|
|
I&5 & $0-(1/19 + 5/8 +2/3)= -613/456 $&-0.69808\\
|
||
|
|
\end{tabular}
|
||
|
|
\end{center}
|
||
|
|
Score residuals at $\beta=0$ are
|
||
|
|
\begin{center}
|
||
|
|
\begin{tabular}{cc|r}
|
||
|
|
Id &Time& Score \\ \hline
|
||
|
|
A&1 &$(2-13/19)(1-1/19)$\\
|
||
|
|
B&1 &$(0-13/19)(0-1/19)$\\
|
||
|
|
C&2 &$ (1-13/19)(0-1/19) + (1-11/16)(1-5/8) $ \\
|
||
|
|
D&2 &$(1-13/19)(0-1/19) + (1-11/16)(1-5/8)$ \\
|
||
|
|
E&2 &$(0-13/19)(0-1/19) + (0-11/16)(1-5/8)$ \\
|
||
|
|
F&2 &$(1-13/19)(0-1/19) + (1-11/16)(0-5/8)$ \\
|
||
|
|
G&3 &$(1-13/19)(0-1/19) + (0-11/16)(0-5/8)$ \\
|
||
|
|
H&4 &$(1-13/19)(0-1/19) + (1-11/16)(0-5/8) $ \\
|
||
|
|
&& $ + (1-2/3)(1-2/3)$ \\
|
||
|
|
I&5 &$(1-13/19)(0-1/19) + (1-11/16)(0-5/8)$ \\
|
||
|
|
& &$+ (0-2/3)(0-2/3) $ \\
|
||
|
|
\end{tabular}
|
||
|
|
\end{center}
|
||
|
|
|
||
|
|
{\splus} also returns unweighted residuals by default, with an option to
|
||
|
|
return the weighted version;
|
||
|
|
it is the weighted sum of residuals that totals zero, $\sum w_i \Mhat_i=0$.
|
||
|
|
Whether the weighted or the unweighted form is more useful depends on the
|
||
|
|
intended application, neither is more ``correct'' than the other.
|
||
|
|
{\splus} does differ for the dfbeta residuals, for which the default is
|
||
|
|
to return weighted values. For the third observation in this data set,
|
||
|
|
for instance, the unweighted dfbeta is an approximation to the change in
|
||
|
|
$\bhat$ that will occur if the case weight is changed from 2 to 3,
|
||
|
|
corresponding to deletion of one of the three ``subjects'' that this
|
||
|
|
observation represents, and the weighted form approximates a change in
|
||
|
|
the case weight from 0 to 3, i.e., deletion of the entire observation.
|
||
|
|
|
||
|
|
The increments of the Nelson-Aalen estimate of the hazard are shown
|
||
|
|
in the rightmost column of table \ref{tab:val3}.
|
||
|
|
The hazard estimate for a hypothetical subject with covariate $X^\dagger$ is
|
||
|
|
$\Lambda_i(t) = \exp(X^\dagger \beta) \Lambda_0(t)$ and the survival
|
||
|
|
estimate is $S_i(t)= \exp(-\Lambda_i(t))$.
|
||
|
|
The two term of the variance, for $X^\dagger=0$, are Term1 + $d'Vd$:
|
||
|
|
\begin{center}
|
||
|
|
\begin{tabular}{c|l}
|
||
|
|
Time & Term 1 \\ \hline
|
||
|
|
1& $1/(r^2 + 11r+7)^2$ \\
|
||
|
|
2& $1/(r^2 + 11r+7)^2 + 10/(11r+5)^2$ \\
|
||
|
|
4& $1/(r^2 + 11r+7)^2 + 10/(11r+5)^2 + 2/(2r+1)^2$ \\
|
||
|
|
\multicolumn{2}{c}{} \\
|
||
|
|
Time & $d$ \\ \hline
|
||
|
|
1& $(2r^2+11r)/(r^2+11r+7)^2$ \\
|
||
|
|
2& $(2r^2+11r)/(r^2+11r+7)^2 + 110r/(11r+5)^2$ \\
|
||
|
|
4& $(2r^2+11r)/(r^2+11r+7)^2 + 110r/(11r+5)^2 + 4r/(2r+1)^2$
|
||
|
|
\end{tabular}
|
||
|
|
\end{center}
|
||
|
|
|
||
|
|
For $\beta=\log(2)$ and $X^\dagger =0$,
|
||
|
|
where $k\equiv$ the variance of
|
||
|
|
$\bhat$ = 1/2.153895 this reduces to
|
||
|
|
\begin{center}
|
||
|
|
\begin{tabular}{c|ll}
|
||
|
|
Time & \multicolumn{2}{c}{Variance}\\ \hline
|
||
|
|
1 & 1/1089 &+ $k(30/1089)^2$ \\
|
||
|
|
2 & (1/1089+ 10/729) &+ $k(30/1089+ 220/729)^2 $ \\
|
||
|
|
4 & (1/1089+ 10/729 + 2/25)&+ $k(30/1089+ 220/729 + 8/25)^2$\\
|
||
|
|
\end{tabular}
|
||
|
|
\end{center}
|
||
|
|
giving numeric values of 0.0012706, 0.0649885, and 0.2903805,
|
||
|
|
respectively.
|
||
|
|
|
||
|
|
\subsection{Efron approximation}
|
||
|
|
For the Efron approximation the combination of tied times and case weights
|
||
|
|
can be approached in at least two ways.
|
||
|
|
One is to treat the case weights as replication counts. There are then
|
||
|
|
10 tied deaths at time 2 in the data above, and the Efron approximation
|
||
|
|
involves 10 different denominator terms.
|
||
|
|
Let $a= 7r+3$, the sum of risk scores for the 3 observations with an event
|
||
|
|
at time 2 and $b=4r+2$, the sum of risk scores for the other subjects at
|
||
|
|
risk at time 2.
|
||
|
|
For the replication approach, the loglikelihood is
|
||
|
|
\begin{eqnarray*}
|
||
|
|
LL &=& \{2\beta - \log(r^2 + 11r +7)\} + \\
|
||
|
|
&& \{7\beta - \log(a+b) - \log(.9a+b) - \ldots - \log(.1a+b) \} + \\
|
||
|
|
&& \{2\beta - \log(2r+1) - \log(r+1)\}.
|
||
|
|
\end{eqnarray*}
|
||
|
|
A test program can be created by comparing results from the weighted
|
||
|
|
data set (9 observations) to the unweighted replicated data set (19
|
||
|
|
observations).
|
||
|
|
This is the approach taken by SAS \code{phreg} using the \code{freq}
|
||
|
|
statement. It's advantage is that the appropriate
|
||
|
|
result for all of the weighted computations is perfectly clear
|
||
|
|
the disadvantage is that the only integer case weights are supported.
|
||
|
|
(A secondary advantage is that I did not need to create another
|
||
|
|
algebraic derivation for this appendix.)
|
||
|
|
|
||
|
|
A second approach, used in the survival package, allows for non-integer weights.
|
||
|
|
The data is considered to be 3 tied observations, and the
|
||
|
|
log-likelihood at time 2 is the sum of 3 weighted terms.
|
||
|
|
The first term of the three is one of
|
||
|
|
\begin{eqnarray*}
|
||
|
|
&& 3 [\beta - \log(a+b)] \\
|
||
|
|
&& 4 [\beta - \log(a+b)] \\
|
||
|
|
&{\rm or}&3 [0 - \log(a+b)],
|
||
|
|
\end{eqnarray*}
|
||
|
|
depending on whether the event for observation C, D or E
|
||
|
|
actually happened first
|
||
|
|
(had we observed the time scale more exactly);
|
||
|
|
the leading multiplier of 3, 4 or
|
||
|
|
3 is the case weight.
|
||
|
|
The second term is one of
|
||
|
|
\begin{eqnarray*}
|
||
|
|
&& 4 [\beta - \log(4s+3+b)] \\
|
||
|
|
&& 3 [0 - \log(4s+3+b)] \\
|
||
|
|
&& 3 [\beta - \log(3s+3+b)] \\
|
||
|
|
&& 3 [\beta - \log(3s+3+b)] \\
|
||
|
|
&& 3 [0 - \log(4s+3+b)] \\
|
||
|
|
&{\rm or}&4 [\beta - \log(4s+3+b)].
|
||
|
|
\end{eqnarray*}
|
||
|
|
The first choice corresponds to an event order of observation C then D
|
||
|
|
(subject D has the event, with D and E still at risk), the
|
||
|
|
second to $C \rightarrow E$, then $D\rightarrow C$, $D\rightarrow E$,
|
||
|
|
$E \rightarrow C$ and $E \rightarrow D$, respectively.
|
||
|
|
For a weighted Efron approximation first replace the argument to the $\log$
|
||
|
|
function by its average argument, just as in the unweighted case.
|
||
|
|
Once this is done the average term in the above corresponds to using an
|
||
|
|
average weight of 10/3.
|
||
|
|
|
||
|
|
|
||
|
|
The final log-likelihood and score statistic are
|
||
|
|
\begin{eqnarray*}
|
||
|
|
LL &=& \{2\beta - \log(r^2 + 11r +7)\} \\ && +
|
||
|
|
\{7\beta - (10/3)[\log(a+b) + \log(2a/3 +b) + \log(a/3+b)] \} \\&& +
|
||
|
|
2\{\beta - \log(2r+1) \} \\ \\
|
||
|
|
U &=& (2- \xbar_1) + 2(1-\xbar_3) \\
|
||
|
|
&& + 7 - (10/3)[\xbar_2 + 26r/(26r+12) + 19r/(19r+9)] \\
|
||
|
|
&=& 11 -(\xbar_1 + (10/3)(\xbar_2 + \xbar_{2b} +\xbar_{2c})
|
||
|
|
+ 2\xbar_3)\\ \\
|
||
|
|
I &=& [(4s^2+11s)/(s^2+11s+7)- \xbar_1^2] \\
|
||
|
|
&&+ (10/3)[ (\xbar_2- \xbar_2^2) + (\xbar_{2b}- \xbar_{2b}^2)
|
||
|
|
+ (\xbar_{2b}- \xbar_{2b}^2) \\
|
||
|
|
&&+2(\xbar_3 - \xbar_3^2) \\
|
||
|
|
\end{eqnarray*}
|
||
|
|
The solution is at $\beta=.87260425$, and
|
||
|
|
$$
|
||
|
|
\begin{array}{ll}
|
||
|
|
LL(0)=-30.29218 & LL(\bhat)=-29.41678 \\
|
||
|
|
U(0) = 2.148183 & U(\bhat) = 0 \\
|
||
|
|
\imat(0) = 2.929182 & \imat(\bhat) = 1.969447 \,.
|
||
|
|
\end{array}
|
||
|
|
$$
|
||
|
|
|
||
|
|
The hazard increment and mean at times 1 and 4 are identical to those
|
||
|
|
for the Breslow approximation, as shown in table \ref{tab:val3}.
|
||
|
|
At time 2, the number at risk for the first, second and third portions
|
||
|
|
of the hazard increment
|
||
|
|
are $n_1= 11r+5$, $n_2= (2/3)(7r+3) + 4r+2 = (26r+12)/3$, and
|
||
|
|
$n_3=(1/3)(7r+3) + 4r+2 = (19r+9)/3$.
|
||
|
|
Subjects F--I experience the full hazard at time 2
|
||
|
|
of $(10/3)(1/n_1 + 1/n_2 + 1/n_3)$,
|
||
|
|
subjects B--D experience $(10/3)(1/n_1 + 2/3n_2 + 1/3n_3)$.
|
||
|
|
Thus, at $\beta=0$ the martingale residuals are
|
||
|
|
\begin{center}
|
||
|
|
\begin{tabular}{cc|ll}
|
||
|
|
Id& Time & \multicolumn{1}{c}{$\Mhat(0)$} \\ \hline
|
||
|
|
A & 1 & 1 - 1/19 & = 18/19 \\
|
||
|
|
B & 1 & 0 - 1/19 & = -1/19 \\
|
||
|
|
C & 2 & 1 - (1/19 + 10/48 + 20/114 + 10/84)& =473/1064 \\
|
||
|
|
D & 2 & 1 - (1/19 + 10/48 + 20/114 + 10/84)& =473/1064 \\
|
||
|
|
E & 2 & 1 - (1/19 + 10/48 + 20/114 + 10/84) &=473/1064 \\
|
||
|
|
F & 2 & 0 - (1/19 + 10/48 + 10/38\phantom{4} + 10/28)& =-2813/3192 \\
|
||
|
|
G & 3 & 0 - (1/19 + 10/48 + 10/38\phantom{4} + 10/28) &=-2813/3192 \\
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H & 4 & 1 - (1/19 + 10/48 + 10/38\phantom{4} + 10/28 + 2/3) &=-1749/3192 \\
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I & 5 & 0 - (1/19 + 10/48 + 10/38\phantom{4} + 10/28 + 2/3) &=-4941/3192
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\end{tabular}
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\end{center}
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The hazard estimate for a hypothetical subject with covariate $X^\dagger$ is
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$\Lambda_i(t) = \exp(X^\dagger \beta) \Lambda_0(t)$,
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$\Lambda_0$ has increments of $1/(r^2 + 11r +7$,
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$(10/3)(1/n_1 + 1/n_2 + 1/n_3)$ and $2/(2r+1)$.
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This increment at time 2 is a little larger than the Breslow jump of
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$10/d1$.
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The first term of the variance will have an increment of
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$[\exp((X^\dagger \beta)(]^2 (10/3)(1/n_1^2 + 1/n_2^2 + 1/n_3^2)$ at time 2.
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The increment to the cumulative distance from the center $d$ will be
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\begin{eqnarray*}
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&& [X^\dagger - \frac{11r}{11r+5}] \frac{10}{3 n_1} \\
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&+& [X^\dagger -\frac{(2/3)7r + 4r}{n2} ] (10/3)(1/n_2) \\
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&+& [X^\dagger -\frac{(1/3)7r + 4r}{n2} ] (10/3)(1/n_3)
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|
\end{eqnarray*}
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|
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For $X^\dagger = 1$ and $\beta=\pi/3$ we get cumulative hazard and variance
|
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|
|
below. We have $r\equiv e^\pi/3$, $V$=
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|
|
%\begin{tabular}{l$=$l|l$+$l$=$r}
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|
|
%\multicolumn{2}{c}{$\Lambda$} & \multicolumn{3}{c}{Variance} \\ \hline
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|
|
%e/(r^2+ 11r+7) & 0.03272832 & e^2/(r^2+ 11r+7)^2 &
|
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|
|
|
||
|
|
|
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|
|
\section{Multi-state data}
|
||
|
|
\begin{figure}
|
||
|
|
<<mstate1, echo=FALSE, fig=TRUE>>=
|
||
|
|
states <- c("Entry", "a", "b", "c")
|
||
|
|
smat <- matrix(0, 4, 4, dimnames=list(states, states))
|
||
|
|
smat[1,2:3] <- 1
|
||
|
|
smat[2,3] <- smat[3,2] <- smat[3,4] <- smat[2,4] <- 1
|
||
|
|
statefig(c(1,2,1), smat)
|
||
|
|
@
|
||
|
|
\caption{A simple 4 state model.}
|
||
|
|
\label{mstate1}
|
||
|
|
\end{figure}
|
||
|
|
|
||
|
|
Figure \ref{mstate1} shows a simple multi-state model, while table
|
||
|
|
\ref{mstate1t} shows a data set for the model.
|
||
|
|
Subject 1 follows the path of Entry, a, b, a, with no further follow
|
||
|
|
up after the final transition, while subjects 4 and 5 are 'censored';
|
||
|
|
they have further follow-up after the last observed change of state.
|
||
|
|
|
||
|
|
\begin{table} \centering
|
||
|
|
\begin{tabular}{ccrcc}
|
||
|
|
id & time1& time2 & event x \\ \hline
|
||
|
|
1 & 0 & 4 & a & 0 \\
|
||
|
|
1 & 4 & 9 & b & 0 \\
|
||
|
|
1 & 9 & 10 & a & 0 \\
|
||
|
|
2 & 0 & 5 & b & 1 \\
|
||
|
|
3 & 2 & 9 & c & 1 \\
|
||
|
|
4 & 0 & 2 & a & 0 \\
|
||
|
|
4 & 2 & 8 & c & 0\\
|
||
|
|
4 & 8 & 9 & & 0 \\
|
||
|
|
5 & 1 & 3 & b & 2\\
|
||
|
|
5 & 3 & 11 & & 2
|
||
|
|
\end{tabular}
|
||
|
|
\caption{A multi-state data set.}
|
||
|
|
\label{mstate1t}
|
||
|
|
\end{table}
|
||
|
|
|
||
|
|
(This section not yet finished.)
|
||
|
|
|
||
|
|
\bibliographystyle{plain}
|
||
|
|
\bibliography{refer}
|
||
|
|
\end{document}
|