Survival Analysis with visR using CDISC ADaM Time-To-Event Analysis Dataset (ADTTE)

Introduction

This tutorial illustrates how a standard time-to-event analysis can be done very efficiently when the data set adheres to the CDISC ADaM standard. A more detailed time-to-event analysis with a more broad overview of visR’s functionality is presented in another vignette.

library(ggplot2)
library(visR)

Global Document Setup

# Metadata Title
DATASET <- paste0("Analyis Data Time-To-Event (ADTTE)")

# Save original options()
old <- options()  

# Global formatting options
options(digits = 3)

# Global ggplot settings
theme_set(theme_bw())

# Global table settings 
options(DT.options = list(pageLength = 10, 
                          language = list(search = 'Filter:'), 
                          scrollX = TRUE))

# load ADTTE from CDISC pilot 
data(adtte)

# Restore original options()
options(old)

Time-to-event analysis

visR includes a wrapper function to easily display summary tables (e.g. tableone)

# Display a summary table (e.g. tableone)
visR::tableone(adtte[,c("TRTP", "AGE")],
         title = "Demographic summary" , datasource = DATASET)
#> Warning: There was 1 warning in `summarise()`.
#> ℹ In argument: `TRTP = (function (x) ...`.
#> ℹ In group 1: `all = "Total"`.
#> Caused by warning:
#> ! `fct_explicit_na()` was deprecated in forcats 1.0.0.
#> ℹ Please use `fct_na_value_to_level()` instead.
#> ℹ The deprecated feature was likely used in the visR package.
#>   Please report the issue at <https://github.com/openpharma/visR/issues>.

Demographic summary
	Total (N=254)
TRTP
Placebo	86 (33.9%)
Xanomeline High Dose	84 (33.1%)
Xanomeline Low Dose	84 (33.1%)
AGE
Mean (SD)	75.1 (8.25)
Median (IQR)	77 (70-81)
Min-max	51-89
Missing	0 (0%)
Data Source: Analyis Data Time-To-Event (ADTTE)

The wrapper function to estimate a Kaplan-Meier curve is compatible with %>% and purrr::map functions without losing traceability of the dataset name inside the call of the object. If a data set adheres to the CDISC ADaM standards, only a stratifier needs to be specified.

# Estimate a survival object
survfit_object <-  adtte %>%
  visR::estimate_KM(data = ., strata = "TRTP")
#> Warning: `estimate_KM()` was deprecated in visR 0.4.0.
#> ℹ Please use `ggsurvfit::ggsurvfit()` instead.
#> This warning is displayed once every 8 hours.
#> Call `lifecycle::last_lifecycle_warnings()` to see where this warning was
#> generated.
survfit_object
#> Call: ~survival::survfit(formula = survival::Surv(AVAL, 1 - CNSR) ~ 
#>     TRTP, data = data)
#> 
#>                            n events median 0.95LCL 0.95UCL
#> TRTP=Placebo              86     29     NA      NA      NA
#> TRTP=Xanomeline High Dose 84     61     36      25      47
#> TRTP=Xanomeline Low Dose  84     62     33      28      51

Given a survival object, visR includes several functions to quickly extract additional information from the survival object (e.g. test statistics and p-values) and a general function to display a table (render).

# Display test statistics associated with the survival estimate

visR::render(survfit_object %>% get_pvalue(), title = "P-values", datasource = DATASET)

P-values
Equality across strata	Chisq	df	p-value
Log-Rank	60.270	2.00	<0.001
Wilcoxon	48.023	2.00	<0.001
Tarone-Ware	41.850	2.00	<0.001
Data Source: Analyis Data Time-To-Event (ADTTE)

A survival object can be plotted using the visR function visr. Additional information like confidence intervals and a risktable can be added to the plot.

# Create and display a Kaplan-Meier from the survival object and add a risktable
visr(survfit_object) %>% 
  visR::add_CI() %>%
  visR::add_risktable()
#> Warning: `visr.survfit()` was deprecated in visR 0.4.0.
#> ℹ Please use `ggsurvfit::ggsurvfit()` instead.
#> This warning is displayed once every 8 hours.
#> Call `lifecycle::last_lifecycle_warnings()` to see where this warning was
#> generated.