Kaplan Meier Curve Data Preparation

library(dplyr)
library(safetyData)
library(DT)

The data

We will use the CDISC Pilot study (CDISCPILOT01), a public mock Alzheimer’s trial of xanomeline patches vs. placebo. It ships as R data frames in the {safetyData} package, so anyone can reproduce this post.

The endpoint is Time to First Dermatologic Event (skin reactions at the patch site). The R Consortium submitted this same KM figure to the FDA in its R-based Submission Pilot 3, and the ADaM data behind it was built with {admiral}. So this isn’t a toy example.

ADAM Dataset: ADTTE

Analysis Dataset for Time-To-Event

To build a Kaplan-Meier curve we need one ADaM dataset, ADTTE, which is derived from ADSL and ADAE. Visually, ADTTE looks like this:

adtte <- safetyData::adam_adtte %>% 
  datatable(
    class = "compact nowrap stripe hover",
    rownames = FALSE,
    filter = "top",
    options = list(
      scrollX = TRUE,
      pagelength = 10,
      autoWidth = TRUE
    )
  )
adtte

ADTTE column descriptions

Variable	Name	In this study
STUDYID	Study Identifier	Always CDISCPILOT01; identifies the trial
SITEID	Study Site Identifier	Which of the 17 clinical sites enrolled the patient (701–718)
USUBJID	Unique Subject Identifier	The patient key (e.g., 01-701-1015) that links ADTTE to every other dataset; 254 patients, one row each
AGE	Age	Age in years at baseline (51–89)
AGEGR1	Pooled Age Group 1	Age category: <65, 65-80, >80
AGEGR1N	Pooled Age Group 1 (N)	Numeric code for AGEGR1 (1, 2, 3), used for sorting
RACE	Race	WHITE, BLACK OR AFRICAN AMERICAN, AMERICAN INDIAN OR ALASKA NATIVE
RACEN	Race (N)	Numeric code for RACE, used for sorting
SEX	Sex	F or M
TRTSDT	Date of First Exposure to Treatment	First dose date; copied from ADSL
TRTEDT	Date of Last Exposure to Treatment	Last dose date; copied from ADSL
TRTDUR	Duration of Treatment (days)	Days on treatment, from TRTSDT to TRTEDT (1–212)
TRTP	Planned Treatment	The arm the patient was assigned to
TRTA	Actual Treatment	The arm the patient actually received; the grouping variable for the KM curves
TRTAN	Actual Treatment (N)	Numeric code for TRTA: 0 = Placebo, 54 = Low Dose, 81 = High Dose (the daily dose in mg)
PARAM	Parameter Description	Time to First Dermatologic Event; the full name of the endpoint
PARAMCD	Parameter Code	TTDE, so we filter to the endpoint we want
AVAL	Analysis Value	Number of days from STARTDT to ADT, counting the start day as Day 1; the x-axis of the KM curve
STARTDT	Time-to-Event Origin Date	Day 1 of the clock; here it’s the first dose date (TRTSDT)
ADT	Analysis Date	The date the clock stopped, either the event date or the censoring date
CNSR	Censor	0 = had a dermatologic event, 1 = censored
EVNTDESC	Event or Censoring Description	Why the clock stopped: Dematologic Event Occured (typo is in the original data) or Study Completion Date
SRCDOM	Source Domain	Which dataset ADT came from: ADAE for events, ADSL for censored patients
SRCVAR	Source Variable	Which column ADT came from: ASTDT (AE start date) or RFENDT (end-of-study date)
SRCSEQ	Source Sequence Number	Which row in ADAE the event came from (matches AESEQ); blank for censored patients
SAFFL	Safety Population Flag	Y = received at least one dose; all 254 patients are in the safety population