This package computes pseudo-observations for recurrent event data in the presence of terminal events. Three versions exist: One-dimensional, two-dimensional or three-dimensional pseudo-observations.
Following the computation of pseudo-observations, the marginal mean function, survival probability and/or cumulative incidences can be modelled using generalised estimating equations.
See Furberg et al. (Bivariate pseudo-observations for recurrent event analysis with terminal events (2021)) for technical details on the procedure.
# Development version
#require(devtools)
#devtools::install_github("JulieKFurberg/recurrentpseudo", force = TRUE)
require(recurrentpseudo)
# Main functions
#?pseudo.onedim
#?pseudo.twodim
#?pseudo.threedim
#?pseudo.geefit
Let \(D^*\) denote the survival time and let \(N^*(t)\) denote the number of recurrent events by time \(t\). Let \(C\) denote the time of censoring. Due to right-censoring, the data consists of \(X=\lbrace N(\cdot), D, \delta, Z \rbrace\) where \(N(t) = N^*(t \wedge C)\), \(D=D^* \wedge C\), \(\delta = I \left( D^* \leq C \right)\) and \(Z\) denotes \(p\) baseline covariates.
We observe \(X_i=\lbrace N_i(\cdot), D_i, \delta_i, Z_i \rbrace\) for each individual \(i= 1,\ldots, n\).
We consider the marginal mean function, \(\mu (t)\), given by \[ \mu(t) = E(N^*(t)) = \int_0^t S(u^-) \, d R(u), \quad d R(t) = E(dN^*(t) \mid D^* \geq t) \] and the survival probability, \(S(t)\), given by \[ S(t) = P(D^*> t). \]
Moreover, we consider the cumulative incidences for death causes 1, \(C_1(t)\), and 2, \(C_2(t)\) \[ C_1(t) = E(I(D^* \leq t, \Delta = 1)), \quad C_2(t) = E(I(D^* \leq t, \Delta = 2)) \] where \(\Delta = \lbrace 1, 2 \rbrace\) represents a cause-of-death indicator.
The following section serves as a fast introduction to pseudo-observations, which the methods of this package is based on.
For more detailed information, please see
Andersen and Perme (Pseudo-observations in survival analysis (2010)) or
Andersen, Klein and Rosthøj (Generalised linear models for correlated pseudo-observations, with applications to multi-state models (2003))
We wish to formulate a model for \[ \theta = E(f(X)) \] where \(X=X_1, \ldots, X_n\) denotes a vector of survival times (or other survival data) for \(n\) individuals and \(f\) denotes some function. An example would be \(\theta = E(I(D^*>t)) = P(D^*>t)\).
Assume that a sufficiently nice estimator \(\hat{\theta}\) of \(\theta\) exists. For a fixed time, \(t \in [0, \tau]\), the pseudo-observation for the i’th individual at \(t\) is given by \[ \hat{\theta}_i (t)= n \cdot \hat{\theta}(t) - (n-1) \cdot \hat{\theta}^{-i}(t) \] where \(\hat{\theta}(t)\) denotes the estimate based on the total data set, and \(\hat{\theta}^{-i}(t)\) denotes the estimate based on the same data set but omitting observations from individual i.
Since the survival times are subject to right-censoring, standard inference on survival data is adjusted to accommodate this, e.g. in likelihood estimation.
However, since all subjects has a valid pseudo-observation, \(\hat{\theta}_i (t)\), at one or more times, these can be used as an outcome variable in a generalised linear model. Note, that this is regardless of the whether a subject is alive, censored or died at time t.
Assume that \(g\) denotes a link function, then we wish to fit
\[ g(E(f(X) \mid Z)) = \xi^T Z. \] Following, \(f(X)\) is replaced by \(\hat{\theta}_i (\cdot)\) in the model fit.
The model parameters, \(\xi\), are estimated using generalised estimating equations (GEE), see Liang and Zeger (Longitudinal data analysis using generalized linear models (1986)).
The GEE procedure accommodates the fact that each individual can have several (pseudo-)observations.
The one-dimensional pseudo-observations model is based on the parameter \(\theta = \mu(t)\), which is estimated by \[ \hat{\theta} = \hat{\mu}(t) = \int_0^t \hat{S}(u^-) \, d \hat{R}(u), \] where \(\hat{S}(t)\) denotes the Kaplan-Meier estimator of \(S(t)\) and \(\hat{R}(t)\) denotes the Nelson-Aalen estimator of \(R(t)\).
We assume that \[ \log \left( \mu(t \mid Z) \right) = \log(\mu_0(t)) + \beta^T Z. \]
The two-dimensional pseudo-observations model is based on the parameter \(\theta = (\mu(t), S(t))\), which is estimated by \[ \hat{\theta} = \left( \begin{matrix} \hat{\mu}(t) \\ \hat{S}(t) \end{matrix} \right). \]
We assume that \[ \left( \begin{matrix} \log \left(\mu (t \mid Z) \right) \\ \text{cloglog} \left( S( t \mid Z) \right) \end{matrix} \right) = \left( \begin{matrix} \log \left( \mu_0(t) \right) + {\beta}^T {Z} \\ \log \left(\Lambda_0(t)\right) + {\gamma}^T {Z} \end{matrix} \right). \]
The three-dimensional pseudo-observations model is based on the parameter \(\theta = (\mu(t), C_1(t), C_2(t))\), which is estimated by \[ \hat{\theta} = \left( \begin{matrix} \hat{\mu}(t) \\ \hat{C}_1(t) \\ \hat{C}_2(t) \end{matrix} \right) \] where \(\hat{C}_1(t)\) and \(\hat{C}_2(t)\) are the Aalen-Johansen estimates of the cumulative incidences for causes 1, \(C_1(t)\), and 2, \(C_2(t)\), respectively.
We assume that \[ \left( \begin{matrix} \log \left(\mu (t \mid Z) \right) \\ \text{cloglog} \left(1- C_1( t \mid Z) \right) \\ \text{cloglog} \left(1- C_2( t \mid Z) \right) \end{matrix} \right) = \left( \begin{matrix} \log \left( \mu_0(t) \right) + {\beta}^T {Z} \\ \log \left(\Lambda_{10}(t)\right) + {\gamma_1}^T {Z} \\ \log \left(\Lambda_{20}(t)\right) + {\gamma_2}^T {Z} \end{matrix} \right). \]
The functions in recurrentpseudo
will be exemplified
using the well-known bladder cancer data from the survival package. This
data set considers data from a clinical cancer trial conducted by the
Veterans Administration Cooperative Urological Research Group (Byar:
The veterans administration study of chemoprophylaxis for recurrent
stage I bladder tumours: comparisons of placebo, pyridoxine and topical
thiotepa (1980)) Here, 118 patients with stage I bladder cancer
were randomised to receive placebo, pyridoxine or thiotepa. After
randomisation, information on occurrences of superficial bladder tumours
and any deaths were collected.
We focus on the comparison between placebo and thiotepa (\(n=86\) in total). We model recurrent bladder tumours, and adjust for death (cause 1: bladder cancer disease death, cause 2: other causes).
One-, two- and three-dimensional pseudo-observations are computed based on a single time point, \(t=30\) months.
For the comparison between placebo and thiotepa on recurrent bladder tumours, the effect measure of interest is the mean ratio \(\exp(\beta)\).
# Example: Bladder cancer data from survival package
require(survival)
#> Indlæser krævet pakke: survival
# Make a three level status variable
$status3 <- ifelse(bladder1$status %in% c(2, 3), 2, bladder1$status)
bladder1
# Add one extra day for the two patients with start=stop=0
# subset(bladder1, stop <= start)
$id == 1, "stop"] <- 1
bladder1[bladder1$id == 49, "stop"] <- 1
bladder1[bladder1
# Restrict the data to placebo and thiotepa
<- subset(bladder1, treatment %in% c("placebo", "thiotepa"))
bladdersub
# Make treatment variable two-level factor
$Z <- as.factor(ifelse(bladdersub$treatment == "placebo", 0, 1))
bladdersublevels(bladdersub$Z) <- c("placebo", "thiotepa")
head(bladdersub)
#> id treatment number size recur start stop status rtumor rsize enum status3
#> 1 1 placebo 1 1 0 0 1 3 . . 1 2
#> 2 2 placebo 1 3 0 0 1 3 . . 1 2
#> 3 3 placebo 2 1 0 0 4 0 . . 1 0
#> 4 4 placebo 1 1 0 0 7 0 . . 1 0
#> 5 5 placebo 5 1 0 0 10 3 . . 1 2
#> 6 6 placebo 4 1 1 0 6 1 1 1 1 1
#> Z
#> 1 placebo
#> 2 placebo
#> 3 placebo
#> 4 placebo
#> 5 placebo
#> 6 placebo
We fit the univariate pseudo-observation model using the binary treatment indicator as covariate, i.e. we model \[ \log \left( \mu(t \mid Z) \right) = \log(\mu_0(t)) + \beta Z \]
One-dimensional pseudo-observations and GEE fit can be computed using the following code,
# Pseudo observations at t = 30
<- pseudo.onedim(tstart = bladdersub$start,
pseudo_bladder_1d tstop = bladdersub$stop,
status = bladdersub$status3,
id = bladdersub$id,
covar_names = "Z",
tk = c(30),
data = bladdersub)
head(pseudo_bladder_1d$outdata)
#> mu k ts id Z
#> 1 -0.0004269178 1 30 1 placebo
#> 2 -0.0004269178 1 30 2 placebo
#> 3 1.2359654463 1 30 3 placebo
#> 4 1.0739859010 1 30 4 placebo
#> 5 -0.0958639918 1 30 5 placebo
#> 6 1.0122441163 1 30 6 placebo
# GEE fit
<- pseudo.geefit(pseudodata = pseudo_bladder_1d,
fit_bladder_1d covar_names = c("Z"))
fit_bladder_1d#> $xi
#>
#> (Intercept) 0.5590869
#> Zthiotepa -0.4359054
#>
#> $sigma
#> (Intercept) Zthiotepa
#> (Intercept) 0.02662095 -0.02662095
#> Zthiotepa -0.02662095 0.07934314
#>
#> attr(,"class")
#> [1] "pseudo.geefit"
# Treatment differences
<- as.matrix(c(fit_bladder_1d$xi[2]), ncol = 1)
xi_diff_1d
<- c("treat, mu")
mslabels rownames(xi_diff_1d) <- mslabels
colnames(xi_diff_1d) <- ""
xi_diff_1d#>
#> treat, mu -0.4359054
# Variance matrix for differences
<- matrix(c(fit_bladder_1d$sigma[2,2]),
sigma_diff_1d ncol = 1, nrow = 1,
byrow = T)
rownames(sigma_diff_1d) <- colnames(sigma_diff_1d) <- mslabels
sigma_diff_1d#> treat, mu
#> treat, mu 0.07934314
Thus, the estimated mean ratio is \(\exp(\hat{\beta})=\) 0.6466789 (standard error and confidence intervals can be found using the Delta method).
Alternatively, the bivariate pseudo-observation model using the binary treatment indicator as covariate can be fitted, i.e. \[ \left( \begin{matrix} \log \left(\mu (t \mid Z) \right) \\ \text{cloglog} \left( S( t \mid Z) \right) \end{matrix} \right) = \left( \begin{matrix} \log \left( \mu_0(t) \right) + {\beta} {Z} \\ \log \left(\Lambda_0(t)\right) + {\gamma} {Z} \end{matrix} \right) \]
Two-dimensional pseudo-observations and GEE fit can be computed using the following code
# Pseudo observations at t = 30
<- pseudo.twodim(tstart = bladdersub$start,
pseudo_bladder_2d tstop = bladdersub$stop,
status = bladdersub$status3,
id = bladdersub$id,
covar_names = "Z",
tk = c(30),
data = bladdersub)
head(pseudo_bladder_2d$outdata)
#> mu surv k ts id Z
#> 1 -0.0004269178 1.421085e-14 1 30 1 placebo
#> 2 -0.0004269178 1.421085e-14 1 30 2 placebo
#> 3 1.2359654463 8.170875e-01 1 30 3 placebo
#> 4 1.0739859010 8.170875e-01 1 30 4 placebo
#> 5 -0.0958639918 -5.305763e-02 1 30 5 placebo
#> 6 1.0122441163 -5.305763e-02 1 30 6 placebo
# GEE fit
<- pseudo.geefit(pseudodata = pseudo_bladder_2d,
fit_bladder_2d covar_names = c("Z"))
fit_bladder_2d#> $xi
#>
#> esttypemu 0.55908687
#> esttypemu:Zthiotepa -0.43590539
#> esttypesurv -1.41652478
#> esttypesurv:Zthiotepa -0.04800778
#>
#> $sigma
#> esttypemu esttypemu:Zthiotepa esttypesurv
#> esttypemu 0.026620952 -0.026620952 -0.003481085
#> esttypemu:Zthiotepa -0.026620952 0.079343139 0.003481085
#> esttypesurv -0.003481085 0.003481085 0.123251791
#> esttypesurv:Zthiotepa 0.003481085 0.002758847 -0.123251791
#> esttypesurv:Zthiotepa
#> esttypemu 0.003481085
#> esttypemu:Zthiotepa 0.002758847
#> esttypesurv -0.123251791
#> esttypesurv:Zthiotepa 0.260915569
#>
#> attr(,"class")
#> [1] "pseudo.geefit"
# Treatment differences
<- as.matrix(c(fit_bladder_2d$xi[2],
xi_diff_2d $xi[4]), ncol = 1)
fit_bladder_2d
<- c("treat, mu", "treat, surv")
mslabels rownames(xi_diff_2d) <- mslabels
colnames(xi_diff_2d) <- ""
xi_diff_2d#>
#> treat, mu -0.43590539
#> treat, surv -0.04800778
# Variance matrix for differences
<- matrix(c(fit_bladder_2d$sigma[2,2],
sigma_diff_2d $sigma[2,4],
fit_bladder_2d$sigma[2,4],
fit_bladder_2d$sigma[4,4]),
fit_bladder_2dncol = 2, nrow = 2,
byrow = T)
rownames(sigma_diff_2d) <- colnames(sigma_diff_2d) <- mslabels
sigma_diff_2d#> treat, mu treat, surv
#> treat, mu 0.079343139 0.002758847
#> treat, surv 0.002758847 0.260915569
Finally, one could fit the three-dimensional pseudo-observation model to the bladder cancer data.
Three-dimensional pseudo-observations and GEE fit can be computed using the following code
# Add deathtype variable to bladder data
# Deathtype = 1 (bladder disease death), deathtype = 2 (other death reason)
$deathtype <- with(bladdersub, ifelse(status == 2, 1, ifelse(status == 3, 2, 0)))
bladdersubtable(bladdersub$deathtype, bladdersub$status)
#>
#> 0 1 2 3
#> 0 55 132 0 0
#> 1 0 0 2 0
#> 2 0 0 0 20
# Pseudo-observations
<- pseudo.threedim(tstart = bladdersub$start,
pseudo_bladder_3d tstop = bladdersub$stop,
status = bladdersub$status3,
id = bladdersub$id,
deathtype = bladdersub$deathtype,
covar_names = "Z",
tk = c(30),
data = bladdersub)
head(pseudo_bladder_3d$outdata_long)
#> k ts id esttype y Z
#> 1 1 30 1 mu -4.269178e-04 placebo
#> 2 1 30 1 surv 1.421085e-14 placebo
#> 3 1 30 1 cif1 0.000000e+00 placebo
#> 4 1 30 1 cif2 1.000000e+00 placebo
#> 5 1 30 2 mu -4.269178e-04 placebo
#> 6 1 30 2 surv 1.421085e-14 placebo
# GEE fit
<- pseudo.geefit(pseudodata = pseudo_bladder_3d,
fit_bladder_3d covar_names = c("Z"))
fit_bladder_3d#> $xi
#>
#> esttypemu 0.5590869
#> esttypemu:Zthiotepa -0.4359054
#> esttypecif1 -3.7618319
#> esttypecif1:Zthiotepa 0.2930357
#> esttypecif2 -1.5431978
#> esttypecif2:Zthiotepa -0.1005109
#>
#> $sigma
#> esttypemu esttypemu:Zthiotepa esttypecif1
#> esttypemu 0.026620952 -0.026620952 0.01663610
#> esttypemu:Zthiotepa -0.026620952 0.079343139 -0.01663610
#> esttypecif1 0.016636098 -0.016636098 1.07839851
#> esttypecif1:Zthiotepa -0.016636098 0.013359996 -1.07839851
#> esttypecif2 -0.006027688 0.006027688 -0.02642283
#> esttypecif2:Zthiotepa 0.006027688 0.001779996 0.02642283
#> esttypecif1:Zthiotepa esttypecif2 esttypecif2:Zthiotepa
#> esttypemu -0.01663610 -0.006027688 0.006027688
#> esttypemu:Zthiotepa 0.01336000 0.006027688 0.001779996
#> esttypecif1 -1.07839851 -0.026422825 0.026422825
#> esttypecif1:Zthiotepa 2.01305239 0.026422825 -0.057715255
#> esttypecif2 0.02642283 0.138167379 -0.138167379
#> esttypecif2:Zthiotepa -0.05771525 -0.138167379 0.299045959
#>
#> attr(,"class")
#> [1] "pseudo.geefit"
# Treatment differences
<- as.matrix(c(fit_bladder_3d$xi[2],
xi_diff_3d $xi[4],
fit_bladder_3d$xi[6]), ncol = 1)
fit_bladder_3d
<- c("treat, mu", "treat, cif1", "treat, cif2")
mslabels rownames(xi_diff_3d) <- mslabels
colnames(xi_diff_3d) <- ""
xi_diff_3d#>
#> treat, mu -0.4359054
#> treat, cif1 0.2930357
#> treat, cif2 -0.1005109
# Variance matrix for differences
<- matrix(c(fit_bladder_3d$sigma[2,2],
sigma_diff_3d $sigma[2,4],
fit_bladder_3d$sigma[2,6],
fit_bladder_3d
$sigma[2,4],
fit_bladder_3d$sigma[4,4],
fit_bladder_3d$sigma[4,6],
fit_bladder_3d
$sigma[2,6],
fit_bladder_3d$sigma[4,6],
fit_bladder_3d$sigma[6,6]
fit_bladder_3d
),ncol = 3, nrow = 3,
byrow = T)
rownames(sigma_diff_3d) <- colnames(sigma_diff_3d) <- mslabels
sigma_diff_3d#> treat, mu treat, cif1 treat, cif2
#> treat, mu 0.079343139 0.01336000 0.001779996
#> treat, cif1 0.013359996 2.01305239 -0.057715255
#> treat, cif2 0.001779996 -0.05771525 0.299045959
We can compare the three model fits. Note, that the \(\mu\) components match each other.
# Compare - should match for mu elements
xi_diff_1d#>
#> treat, mu -0.4359054
xi_diff_2d#>
#> treat, mu -0.43590539
#> treat, surv -0.04800778
xi_diff_3d#>
#> treat, mu -0.4359054
#> treat, cif1 0.2930357
#> treat, cif2 -0.1005109
sigma_diff_1d#> treat, mu
#> treat, mu 0.07934314
sigma_diff_2d#> treat, mu treat, surv
#> treat, mu 0.079343139 0.002758847
#> treat, surv 0.002758847 0.260915569
sigma_diff_3d#> treat, mu treat, cif1 treat, cif2
#> treat, mu 0.079343139 0.01336000 0.001779996
#> treat, cif1 0.013359996 2.01305239 -0.057715255
#> treat, cif2 0.001779996 -0.05771525 0.299045959
Assume that we wish to add extra baseline covariates to the model fit. For the sake of illustration, we have simulated a continuous covariate, \(Z_2\), and a categorical covariate, \(Z_3\). The covariate \(Z_1\) corresponds to the binary treatment covariate (\(Z=1\) is thiotepa and \(Z=0\) is placebo). In order to make estimation for these models possible, the pseudo-observations are calculated at three time points, namely \(t=20, 30, 40\) months.
For the one-dimensional model for \(\mu\) it holds that,
\[ \log \left( \mu(t \mid Z) \right) = \log(\mu_0(t)) + \beta_1 Z_1 + \beta_2 Z_2 + \beta_3 Z_3. \]
This can be fitted using the below code,
require(dplyr)
## One-dim
# A binary variable, Z1_
# A continuous variable, Z2_
# A categorical variable, Z3_
set.seed(0308)
<- as.data.frame(
bladdersub %>% group_by(id) %>%
bladdersub mutate(Z1_ = Z,
Z2_ = rnorm(1, mean = 3, sd = 1),
Z3_ = sample(x = c("A", "B", "C"),
size = 1, replace = TRUE,
prob = c(1/4, 1/2, 1/4))
))# head(bladdersub, 20)
# Make pseudo obs at more timepoints (more data)
# Pseudo observations at t = 20, 30, 40
<- pseudo.onedim(tstart = bladdersub$start,
pseudo_bladder_1d_3t tstop = bladdersub$stop,
status = bladdersub$status3,
id = bladdersub$id,
covar_names = c("Z1_", "Z2_", "Z3_"),
tk = c(20, 30, 40),
data = bladdersub)
<- pseudo.geefit(pseudodata = pseudo_bladder_1d_3t,
fit1 covar_names = c("Z1_", "Z2_", "Z3_"))
$xi
fit1#>
#> (Intercept) 0.39412273
#> Ztime30 0.42336922
#> Ztime40 0.59966454
#> Z1_thiotepa -0.29479824
#> Z2_ -0.08253287
#> Z3_B 0.01965615
#> Z3_C -0.38332247
$sigma
fit1#> (Intercept) Ztime30 Ztime40 Z1_thiotepa Z2_
#> (Intercept) 0.136673486 -0.0061702979 -0.0109943095 -0.036100986 -0.0247560186
#> Ztime30 -0.006170298 0.0046658382 0.0061013009 0.001167246 0.0002746085
#> Ztime40 -0.010994310 0.0061013009 0.0100442253 0.005504053 -0.0004015364
#> Z1_thiotepa -0.036100986 0.0011672458 0.0055040527 0.090063224 -0.0078557067
#> Z2_ -0.024756019 0.0002746085 -0.0004015364 -0.007855707 0.0109918233
#> Z3_B -0.055441417 0.0005892506 0.0051883496 0.037829933 -0.0035769385
#> Z3_C -0.041748863 0.0075014896 0.0141048652 0.023020550 -0.0082026411
#> Z3_B Z3_C
#> (Intercept) -0.0554414168 -0.041748863
#> Ztime30 0.0005892506 0.007501490
#> Ztime40 0.0051883496 0.014104865
#> Z1_thiotepa 0.0378299330 0.023020550
#> Z2_ -0.0035769385 -0.008202641
#> Z3_B 0.0869004239 0.050773663
#> Z3_C 0.0507736625 0.200303239
$xi[4]
fit1#> [1] -0.2947982
Or for two-dimensional pseudo-observations, it holds that
\[ \left( \begin{matrix} \log \left(\mu (t \mid Z) \right) \\ \text{cloglog} \left( S( t \mid Z) \right) \end{matrix} \right) = \left( \begin{matrix} \log \left( \mu_0(t) \right) + \beta_1 {Z_1} + \beta_2 {Z_2} + \beta_3 {Z_3} \\ \log \left(\Lambda_0(t)\right) + {\gamma_1} Z_1 + {\gamma_2} Z_2 + {\gamma_3} Z_3 \end{matrix} \right). \] Or for three-dimensional pseudo-observations, it holds that \[ \left( \begin{matrix} \log \left(\mu (t \mid Z) \right) \\ \text{cloglog} \left(1- C_1( t \mid Z) \right) \\ \text{cloglog} \left( 1-C_2( t \mid Z) \right) \end{matrix} \right) = \left( \begin{matrix} \log \left( \mu_0(t) \right) + {\beta_1} {Z_1} + {\beta_2} {Z_2} + {\beta_3} Z_3\\ \log \left(\Lambda_{10}(t)\right) + \gamma_{11} {Z_1} + \gamma_{12} {Z_2} + \gamma_{13} {Z_3} \\ \log \left(\Lambda_{20}(t)\right) + \gamma_{21} {Z_1} + \gamma_{22} {Z_2} + \gamma_{23} {Z_3} \end{matrix} \right). \]
These two models are fitted using the below code,
## Two-dim
# Pseudo observations at t = 20, 30, 40
<- pseudo.twodim(tstart = bladdersub$start,
pseudo_bladder_2d_3t tstop = bladdersub$stop,
status = bladdersub$status3,
id = bladdersub$id,
covar_names = c("Z1_", "Z2_", "Z3_"),
tk = c(20, 30, 40),
data = bladdersub)
<- pseudo.geefit(pseudodata = pseudo_bladder_2d_3t,
fit2 covar_names = c("Z1_", "Z2_", "Z3_"))
# fit2$xi
# fit2$sigma
## Three-dim
<- pseudo.threedim(tstart = bladdersub$start,
pseudo_bladder_3d_3t tstop = bladdersub$stop,
status = bladdersub$status3,
id = bladdersub$id,
covar_names = c("Z1_", "Z2_", "Z3_"),
deathtype = bladdersub$deathtype,
tk = c(20, 30, 40),
data = bladdersub)
<- pseudo.geefit(pseudodata = pseudo_bladder_3d_3t,
fit3 covar_names = c("Z1_", "Z2_", "Z3_"))
# fit3$xi
# fit3$sigma
## Compare for mu
$xi[4]
fit1#> [1] -0.2947982
$xi[4]
fit2#> [1] -0.2947982
$xi[4]
fit3#> [1] -0.2948043
To cite the recurrentpseudo
package please use the
following references,
Julie K. Furberg, Per K. Andersen, Sofie Korn, Morten Overgaard, Henrik Ravn: Bivariate pseudo-observations for recurrent event analysis with terminal events (Lifetime Data Analysis, 2021)