chapter14.qmd

---
title: "Chapter 14 - Causal Inference in Survival Analysis"
---

## Slides

Lecture slides [here](chap14.html){target="_blank"}. (To convert html to pdf, press E $\to$ Print $\to$ Destination: Save to pdf)

## Base R Code

```{r}
#| code-fold: true
#| code-summary: "Show the code"
#| eval: false

##################################################################
# This code generates all numerical results in chapter 14.     ##
##################################################################


library(survival)
##############################################
# GBC study
#############################################
#read in the complete data
gbc <- read.table("Data//German Breast Cancer Study//gbc.txt")

#subset to first event data
#Sort the data by time within each id
o <- order(gbc$id,gbc$time)
gbc <- gbc[o,]
#get the first row for each id
data.CE <- gbc[!duplicated(gbc$id),]

#set status=1 if status==2 or 1
data.CE$status <- (data.CE$status>0)+0

head(data.CE)


######################
# Section 14.2.3
######################

# create treatment variable A
# A=1: hormone treatment
# A=0: non-treatment
data.CE$A <- data.CE$hormone - 1



# Load the ipw package for propensity score calculation
library(ipw)

# compute propensity score for A against
# menopausal status, tumor size, grade, nodes,
# progesterone and estrogen receptor levels
tmp <- ipwpoint(exposure=A,family="binomial",link="logit",
              denominator=~ meno+size+factor(grade)+nodes+
                  prog+estrg, data=data.CE)

# naive version (unweighted)
obj.naive <- survfit(Surv(time,status)~A,data=data.CE)
# IPTW version (weighted by temp$ipw.weights computed from the
#   ipwpoint() function)
obj <- survfit(Surv(time,status) ~ A,weights = tmp$ipw.weights, data = data.CE)


# IPTW Cox model (essentially a marginal structural Cox model)
coxph(Surv(time,status)~A,weights=tmp$ipw.weights,data=data.CE)

coxph(Surv(time,status)~A,data=data.CE)


#########################################################
# Figure 15.3 Naive and IPTW-adjusted Kaplan--Meier 
# curves for the German Breast Cancer study by treatment
#########################################################
plot(obj.naive, xlim=c(0,80),lwd=2,frame=F, lty=c(2,1),
     xlab="Time (months)",ylab="Relaspe-free survival probabilities",
     cex.lab=1.5,cex.axis=1.5)

lines(obj,col='red',lty=c(2,1), cex.lab=1.5,cex.axis=1.5)
legend(1,0.3,lty=c(2:1,2:1), col=rep(c("black","red"),each=2),
       c("No Hormone (naive)","Hormone (naive)",
         "No Hormone (IPTW)","Hormone (IPTW)"),
       lwd=2,cex=1.5)



################################
# Section 14.3.3 HIV/AIDS study 
################################

# need the ipw package
data("haartdat")
colnames(haartdat)[8] <- "cd4"

head(haartdat)



# Compute the IPTW weights
iptw <- ipwtm(exposure = haartind, family = "survival",
          numerator = ~ sex + age, denominator = ~ cd4 + sex + age,
          id = patient, tstart = tstart, timevar = fuptime, type = "first",
          data = haartdat)

# Compute the IPCW weights
ipcw <- ipwtm(exposure = dropout, family = "survival",
              numerator = ~ sex + age, denominator = ~ cd4 + sex + age,
              id = patient, tstart = tstart, timevar = fuptime, type = "first",
              data = haartdat)

# Fit IPTW/IPCW marginal structural Cox model
obj <- coxph(Surv(tstart, fuptime, event) ~ haartind + sex + age+ 
               cluster(patient), data = haartdat, 
             weights = iptw$ipw.weights*ipcw$ipw.weights)
summary(obj)


# Naive Cox model with time-varying treatment
obj_naive <- coxph(Surv(tstart, fuptime, event) ~ haartind + sex + age+ 
               cluster(patient), data = haartdat)
summary(obj_naive)
```