Time to ae

DESCRIPTION

@@ -34,6 +34,8 @@ Imports:
     rlang,
     shiny,
     stringr,
+    survival,
+    survminer,
     Tendril,
     Tplyr
 Suggests:

NAMESPACE

@@ -20,13 +20,16 @@ export(safetyOutlierExplorer_ui)
 export(safety_outlier_explorer)
 export(safety_results_over_time)
 export(tendril_chart)
+export(timeToAE)
 import(Tendril)
 import(Tplyr)
 import(dplyr)
 import(ggplot2)
 import(htmlwidgets)
 import(rlang)
 import(shiny)
+import(survival)
+import(survminer)
 importFrom(huxtable,as_hux)
 importFrom(huxtable,set_align)
 importFrom(huxtable,set_bold)

R/meta.R

@@ -99,3 +99,23 @@
 #' @source Created for this package
 
 "meta_hepExplorer"
+
+#' Metadata data frame containing information about the data mapping used to configure safetyGraphics for the Time to AE Chart. One record per unique data mapping
+#'
+#' @format A data frame with X rows and 10 columns
+#' \describe{
+#'    \item{domain}{Data domain}
+#'    \item{text_key}{Text key indicating the setting name. \code{'--'} delimiter indicates a field level data mapping}
+#'    \item{col_key}{Key for the column mapping}
+#'    \item{field_key}{Key for the field mapping (if any)}
+#'    \item{type}{type of mapping - "field" or "column"}
+#'    \item{label}{Label}
+#'    \item{description}{Description}
+#'    \item{multiple}{Mapping supports multiple columns/fields }
+#'    \item{standard_adam}{Default values for the ADaM data standard}
+#'    \item{standard_sdtm}{Default values for the SDTM data standard}
+#' }    
+#' 
+#' @source Created for this package
+
+"meta_timeToAE"

R/mod_demogRTF.R

@@ -118,4 +118,4 @@ demogRTF_table <- function(data, settings) {
         pharmaRTF::set_column_header_buffer(top=1)
 
     return(doc)
-}
+}

R/mod_timeToAE.R

@@ -0,0 +1,85 @@
+timeToAE_ui <- function(id) {
+    ns <- NS(id)
+
+    sidebar <- sidebarPanel(
+        selectizeInput(
+            ns('ae'),
+            'Time to',
+            multiple = FALSE,
+            choices = NULL
+        ),
+        selectizeInput(
+            ns('stratum'),
+            'Stratum',
+            multiple = FALSE,
+            choices = NULL
+        )
+    )
+
+    main <- mainPanel(
+        plotOutput(ns('survival_plot'))
+    )
+
+    ui <- fluidPage(
+        sidebarLayout(
+            sidebar,
+            main,
+            position = c('right'),
+            fluid = TRUE
+        )
+    )
+
+    return(ui)
+}
+
+timeToAE_server <- function(input, output, session, params) {
+    ns <- session$ns
+
+    observe({
+        params <- params()
+        data <- params$data
+        settings <- params$settings
+
+        ae_choices <- data$aes %>%
+            group_by(!!sym(settings$aes$term_col)) %>%
+            tally %>%
+            arrange(desc(n)) %>%
+            pull(!!sym(settings$aes$term_col))
+
+        updateSelectizeInput(
+            session,
+            'ae',
+            choices = c('Any AE', ae_choices),
+            selected = 'Any AE'
+        )
+    })
+
+    observe({
+        params <- params()
+        data <- params$data
+        settings <- params$settings
+
+        updateSelectizeInput(
+            session,
+            'stratum',
+            choices = c(
+                'None',
+                settings$dm$treatment_col,
+                settings$dm$sex_col,
+                settings$dm$race_col
+            ),
+            selected = 'None'
+        )
+    })
+
+    output$survival_plot <- renderPlot({
+        params <- params()
+
+        timeToAE(
+            params$data,
+            params$settings,
+            input$ae,
+            input$stratum
+        )
+    })
+}

R/timeToAE.R

@@ -0,0 +1,98 @@
+#' Time to AE
+#'
+#' @param data list of data frames including dataframes named `aes` (adverse events) and `dm` (demographics)
+#' @param settings named list of domain-specific settings with the parameters specified below.
+#' @param ae AE of interest. Default="Any ae"
+#' @param stratum Default='None'
+#' 
+#' @return returns a chart object
+#'
+#' @import survival
+#' @import survminer
+#' @import dplyr
+#'
+#' @export
+#'
+
+timeToAE <- function(data, settings, ae = 'Any AE', stratum = 'None') {
+
+    # Participant-level data
+    participants <- data$dm %>%
+        filter(!is.na(RFSTDTC)) %>%
+        mutate(
+            RFSTDT = as.Date(RFSTDTC),
+            RFENDT = as.Date(RFENDTC)
+        )
+
+    # Event-level data
+    aes <- data$aes %>%
+        filter(
+            ae == 'Any AE' | !!sym(settings$aes$term_col) == ae
+        ) %>%
+        mutate(
+            AESTDT = as.Date(ASTDT)
+        )
+
+    # Get first instance of adverse event for each participant.
+    first_ae <- aes %>%
+        left_join(
+            participants,
+            settings$dm$id_col
+        ) %>%
+        filter(RFSTDT <= AESTDT) %>%
+        arrange(!!sym(settings$dm$id_col), AESTDT) %>%
+        group_by(!!sym(settings$dm$id_col)) %>%
+        filter(row_number() == 1) %>%
+        ungroup %>%
+        select(!!sym(settings$dm$id_col), AESTDT)
+
+    # Get list of participants without adverse event.
+    censored <- setdiff(
+        participants[[settings$dm$id_col]],
+        first_ae[[settings$dm$id_col]]
+    )
+
+    # Merge all participants with participants who experienced an event and define time to event.
+    tte <- participants %>%
+        left_join(
+            first_ae,
+            settings$dm$id_col
+        ) %>%
+        mutate(
+            stdt = RFSTDT,
+            endt = coalesce(AESTDT, RFENDT),
+            time = (endt - stdt + 1) %>% as.numeric,
+            cnsr = (!!sym(settings$dm$id_col) %in% censored) %>% as.numeric,
+            event = !as.logical(cnsr) %>% as.numeric
+        )
+
+    # Define survival formula.
+    fit <- NULL
+    legend.labs <- NULL
+    if (stratum == 'None' | is.null(stratum))
+        fit = survfit(
+            Surv(time, event) ~ 1,
+            data = tte
+        )
+    else {
+        tte$stratum <- tte[[stratum]]
+        legend.labs = unique(tte$stratum)
+        fit = survfit(
+            Surv(time, event) ~ stratum,
+            data = tte
+        )
+    }
+
+    # Plot survival curve.
+    p <- ggsurvplot(
+        fit = fit,
+        data = tte,
+        title = paste('Time to', ae),
+        xlab = 'Study Day',
+        ylab = 'Survival probability',
+        risk.table = TRUE,
+        legend.labs = legend.labs
+    )
+
+    return(p)
+}

data-raw/makeMeta.R

@@ -2,7 +2,7 @@
 library(tidyverse)
 library(usethis)
 
- # brackets after read_csv to remove spec_tbl_df class per https://www.tidyverse.org/blog/2018/12/readr-1-3-1/
+# brackets after read_csv to remove spec_tbl_df class per https://www.tidyverse.org/blog/2018/12/readr-1-3-1/
 
 #Copy metadata to /data
 #ecg
@@ -24,3 +24,7 @@ usethis::use_data(meta_dm, overwrite = TRUE)
 #hepExplorer
 meta_hepExplorer<-read_csv("data-raw/meta_hepExplorer.csv")[]
 usethis::use_data(meta_hepExplorer, overwrite = TRUE)
+
+#time to AE
+meta_timeToAE<-read_csv("data-raw/meta_timeToAE.csv")[]
+usethis::use_data(meta_timeToAE, overwrite = TRUE)

data-raw/meta_timeToAE.csv

@@ -0,0 +1,15 @@
+text_key,domain,col_key,field_key,type,label,description,multiple,standard_adam,standard_sdtm
+id_col,dm,id_col,,column,ID column,Unique subject identifier,FALSE,USUBJID,USUBJID
+treatment_col,dm,treatment_col,,column,Treatment column,Treatment group,FALSE,ARM,ARM
+sex_col,dm,sex_col,,column,Sex column,Sex,FALSE,SEX,SEX
+race_col,dm,race_col,,column,Race column,Race,FALSE,RACE,RACE
+stdt_col,dm,stdt_col,,column,Study start date column,Study start date,FALSE,TRTSDT,RFSTDTC
+endt_col,dm,endt_col,,column,Study end date column,Study end date,FALSE,TRTEDT,RFENDTC
+id_col,aes,id_col,,column,ID column,Unique subject identifier,FALSE,USUBJID,USUBJID
+seq_col,aes,seq_col,,column,Sequence column,Event sequence number,FALSE,ASEQ,AESEQ
+stdt_col,aes,stdt_col,,column,AE start day column,Event start date,FALSE,ASTDT,AESTDT
+endt_col,aes,endt_col,,column,AE end day column,Event end date,FALSE,AENDT,AEENDT
+stdy_col,aes,stdy_col,,column,AE start day column,Event start day,FALSE,ASTDY,AESTDY
+endy_col,aes,endy_col,,column,AE end day column,Event end day,FALSE,AENDY,AEENDY
+term_col,aes,term_col,,column,Dictionary-derived term column,Dictionary-derived term,FALSE,AEDECOD,AEDECOD
+bodsys_col,aes,bodsys_col,,column,Body system or organ class column,Body system or organ class,FALSE,AEBODSYS,AEBODSYS

inst/config/mod_timeToAE.yaml

@@ -0,0 +1,12 @@
+env: safetyGraphics
+label: Time to Adverse Event - Module
+type: module
+package: safetyCharts
+export: true
+order: 2.2
+domain:
+  - aes
+  - dm
+workflow:
+  ui: timeToAE_ui
+  server: timeToAE_server

inst/config/timeToAE.yaml

@@ -0,0 +1,11 @@
+env: safetyGraphics
+label: Time to Adverse Event
+type: plot
+package: safetyCharts
+export: true
+order: 2.1
+domain:
+  - aes
+  - dm
+workflow:
+  main: timeToAE