update ectd R code

vignettes/adrg-prepare.Rmd

@@ -54,24 +54,24 @@ knitr::include_graphics("pdf/tlf-efficacy.pdf")
 ```
 
 ```{r, eval = FALSE}
-knitr::purl("tlf-demographic.Rmd", output = "ectd/tlf-demographic.txt")
-knitr::purl("tlf-efficacy.Rmd",    output = "ectd/tlf-efficacy.txt")
-knitr::purl("tlf-kmplot.Rmd", output = "ectd/tlf-kmplot.txt")
-knitr::purl("tlf-primary.Rmd", output = "ectd/tlf-primary.txt")
+knitr::purl("tlf-demographic.Rmd", output = "ectd/tlf-demographic.r")
+knitr::purl("tlf-efficacy.Rmd",    output = "ectd/tlf-efficacy.r")
+knitr::purl("tlf-kmplot.Rmd", output = "ectd/tlf-kmplot.r")
+knitr::purl("tlf-primary.Rmd", output = "ectd/tlf-primary.r")
 ```
 
 ## List R package for analysis 
 
-CRAN package 
-
 ```{r}
 pkg <- c("haven", "dplyr", "emmeans", "r2rtf","rtables", 
+         "ggplot2", "cowplot", "visR",
          "Tplyr", "pharmaRTF", "huxtable")
 
 available.packages(contriburl = contrib.url(repos)) %>% 
   data.frame() %>% 
   subset(Package %in% pkg) %>% 
-  select(Package, Version, Repository)
+  select(Package, Version, Repository) %>%
+  arrange(Package)
 ```
 
 Proprietary Package 

vignettes/ectd/r0pkg.txt

@@ -108,20 +108,28 @@ Content:
 
   ## Overview
 
-  The objective of the R Cconsortium R submission Pilot 1 Project is to 
+  The objective of the R Consortium R submission Pilot 1 Project is to 
   test the concept that a R-language based submission package can meet 
   the needs and the expectations of the FDA reviewers, 
   including assessing code review and analyses reproducibility. 
-  All submission materials and communications from this pilot is publicly available, 
+  All submission materials and communications from this pilot are publicly available, 
   with the aim of providing a working example for future R language based FDA submissions.
   This is a FDA-industry collaboration through the non-profit organization R consortium.
 
-  The [RConsortium/submissions-pilot1](https://github.com/RConsortium/submissions-pilot1) repo demonstrate an approach to organize internal developed R function and 
+  The [RConsortium/submissions-pilot1](https://github.com/RConsortium/submissions-pilot1) repo demonstrates an approach to organize internal developed R function and 
   table, listing, figure generation program using an R package. 
 
   The [RConsortium/submissions-pilot1-to-fda](https://github.com/RConsortium/submissions-pilot1-to-fda)
-  repo demonstrate the eCTD submission package based on the [RConsortium/submissions-pilot1](https://github.com/RConsortium/submissions-pilot1) repo.  
+  repo demonstrates the eCTD submission package based on the [RConsortium/submissions-pilot1](https://github.com/RConsortium/submissions-pilot1) repo.  
 
+  ## Running Environment 
+
+  The project is developed and tested in the environment below:
+
+  - OS: Ubuntu 20.04
+  - R version: R4.1.0
+  - Snapshot date: 2021-08-31
+  - Snapshot repository: https://mran.microsoft.com/snapshot/2021-08-31
 
   ## Folder Structure 
 
@@ -172,7 +180,7 @@ Content:
   #'
   #' This function handles the necessary data processing to handle the CDISC pilot
   #' primary endpoint analysis. The original source can be found
-  #' \link[here]{https://github.com/atorus-research/CDISC_pilot_replication/blob/3c8e9e3798c02be8d93bd8e8944d1e0d3f6519e2/programs/funcs.R#L401}
+  #' [here](https://github.com/atorus-research/CDISC_pilot_replication/blob/3c8e9e3798c02be8d93bd8e8944d1e0d3f6519e2/programs/funcs.R#L401)
   #'
   #' @importFrom tidyr pivot_longer
   #' @importFrom glue glue
@@ -527,7 +535,7 @@ Content:
   \description{
   This function handles the necessary data processing to handle the CDISC pilot
   primary endpoint analysis. The original source can be found
-  \link[here]{https://github.com/atorus-research/CDISC_pilot_replication/blob/3c8e9e3798c02be8d93bd8e8944d1e0d3f6519e2/programs/funcs.R#L401}
+  \href{https://github.com/atorus-research/CDISC_pilot_replication/blob/3c8e9e3798c02be8d93bd8e8944d1e0d3f6519e2/programs/funcs.R#L401}{here}
   }
 
 Package: pilot1wrappers
@@ -758,6 +766,11 @@ Content:
     \item Eli Miller
   }
 
+  Other contributors:
+  \itemize{
+    \item Steven Haesendonckx [contributor]
+  }
+
   }
   \keyword{internal}
 
@@ -807,7 +820,7 @@ Content:
   }
 
   # Repository
-  message("Current oroject R package repository:")
+  message("Current project R package repository:")
   message(paste0("    ", getOption("repos")))
   message(" ")
 

vignettes/ectd/tlf-demographic.txt → vignettes/ectd/tlf-demographic.r

@@ -6,17 +6,19 @@
 # path = list(adam = "path/to/esub/analysis/adam/datasets")    	# Modify path to the actual location
 # path$outtable = path$outgraph = "."                           # Output saved in current folder
 
+
 library(haven) 
 library(dplyr)
 library(rtables)
 library(pilot1wrappers)
 
 
-## ------------------------------------------------------------------------------------------------------------------
+## -----------------------------------------------------------------------------------------------------------------------------------
 adsl  <- read_xpt(file.path(path$adam, "adsl.xpt")) 
+adsl_labels <- var_labels(adsl)
 
 
-## ------------------------------------------------------------------------------------------------------------------
+## -----------------------------------------------------------------------------------------------------------------------------------
 adsl <- adsl %>%
   dplyr::filter(
     STUDYID == "CDISCPILOT01",
@@ -26,18 +28,19 @@ adsl <- adsl %>%
     TRT01P = factor(TRT01P, levels = c("Placebo", "Xanomeline Low Dose",  "Xanomeline High Dose")),
     AGEGR1 = factor(AGEGR1, levels = c("<65", "65-80", ">80")),
     RACE = factor(RACE, levels = c("WHITE", "BLACK OR AFRICAN AMERICAN", "AMERICAN INDIAN OR ALASKA NATIVE"))
-  )
+  ) 
 
 
-## ------------------------------------------------------------------------------------------------------------------
+## -----------------------------------------------------------------------------------------------------------------------------------
 # Table layout
+vars <- c("AGE", "AGEGR1", "RACE", "HEIGHTBL", "WEIGHTBL", "BMIBL", "MMSETOT")
 lyt <- basic_table(title = "Protocol: CDISCPILOT01",
                    subtitles = "Population: Intent-to-Treat",
-                   main_footer = "Program: tlf_demographic.Rmd" 
+                   main_footer = paste0("Program: tlf_demographic.Rmd \n" , Sys.time())
 ) %>%
   split_cols_by("TRT01P") %>%
   add_colcounts() %>%
-  analyze(c("AGE", "AGEGR1", "RACE", "HEIGHTBL", "WEIGHTBL", "BMIBL", "MMSETOT"), function(x, ...) {
+  analyze(vars, function(x, ...) {
     if (is.numeric(x)) {
       in_rows(
         "Mean (sd)" = c(mean(x), sd(x)),
@@ -50,15 +53,16 @@ lyt <- basic_table(title = "Protocol: CDISCPILOT01",
     } else {
       stop("type not supproted")
     }
-  })
+  },
+  var_labels = adsl_labels[vars])
 
 # Table build
 tbl <- build_table(lyt, adsl)
 
 tbl
 
 
-## ------------------------------------------------------------------------------------------------------------------
+## -----------------------------------------------------------------------------------------------------------------------------------
 # Output .out file 
 tbl %>%
   toString() %>%

vignettes/ectd/tlf-efficacy.txt → vignettes/ectd/tlf-efficacy.r

@@ -7,20 +7,17 @@
 # path$outtable = path$outgraph = "."                           # Output saved in current folder
 
 library(dplyr)
-library(tibble)
-library(tidyr)
 library(haven)
 library(r2rtf)
 library(emmeans)
 library(pilot1wrappers)
 
 
-## ------------------------------------------------------------------------------------------------------------------
-adsl <- read_xpt(file.path(path$adam, "adsl.xpt"))
+## -----------------------------------------------------------------------------------------------------------------------------------
 adlb <- read_xpt(file.path(path$adam, "adlbc.xpt"))
 
 
-## ------------------------------------------------------------------------------------------------------------------
+## -----------------------------------------------------------------------------------------------------------------------------------
 adlb1 <- subset(adlb, TRTPN %in% c(0, 81) & PARAMCD == "GLUC" & !is.na(AVISITN)) %>%
   mutate(TRTPN = ifelse(TRTPN == 0, 99, TRTPN)) # change treatment order for pairwise comparison
 
@@ -64,7 +61,7 @@ apr0ancova1 <- merge(t11, t12) %>%
 apr0ancova1
 
 
-## ------------------------------------------------------------------------------------------------------------------
+## -----------------------------------------------------------------------------------------------------------------------------------
 t2 <- data.frame(pairs(t12))
 
 ## Treatment Comparison
@@ -83,7 +80,7 @@ apr0ancova2 <- t2 %>%
 apr0ancova2
 
 
-## ------------------------------------------------------------------------------------------------------------------
+## -----------------------------------------------------------------------------------------------------------------------------------
 ### Calculate root mean square and save data in output folder
 apr0ancova3 <- data.frame(rmse = paste0(
   "Root Mean Squared Error of Change = ",
@@ -93,7 +90,7 @@ apr0ancova3 <- data.frame(rmse = paste0(
 apr0ancova3
 
 
-## ------------------------------------------------------------------------------------------------------------------
+## -----------------------------------------------------------------------------------------------------------------------------------
 tbl_1 <- apr0ancova1 %>%
   rtf_title(
     title = "ANCOVA of Change from Baseline at Week 20",
@@ -127,7 +124,7 @@ tbl_1 <- apr0ancova1 %>%
   )
 
 
-## ------------------------------------------------------------------------------------------------------------------
+## -----------------------------------------------------------------------------------------------------------------------------------
 tbl_2 <- apr0ancova2 %>%
   rtf_colheader(
     colheader = "Pairwise Comparison | Difference in LS Mean (95% CI){^a} | p-Value",
@@ -141,17 +138,21 @@ tbl_2 <- apr0ancova2 %>%
   )
 
 
-## ------------------------------------------------------------------------------------------------------------------
+## -----------------------------------------------------------------------------------------------------------------------------------
 tbl_3 <- apr0ancova3 %>%
   rtf_body(
     as_colheader = FALSE,
     text_justification = "l"
   )
 
 
-## ------------------------------------------------------------------------------------------------------------------
+## -----------------------------------------------------------------------------------------------------------------------------------
 tbl <- list(tbl_1, tbl_2, tbl_3)
 tbl %>%
   rtf_encode() %>%
   write_rtf(file.path(path$output, "tlf-efficacy.rtf"))
 
+
+## ---- out.width = "100%", out.height = "400px", echo = FALSE, fig.align = "center"--------------------------------------------------
+knitr::include_graphics("pdf/tlf-efficacy.pdf")
+

vignettes/ectd/tlf-kmplot.r

@@ -0,0 +1,91 @@
+# Note to Reviewer 
+# To rerun the code below, please refer ADRG appendix.
+# After required package are installed. 
+# The path variable needs to be defined by using example code below
+#
+# path = list(adam = "path/to/esub/analysis/adam/datasets")    	# Modify path to the actual location
+# path$outtable = path$outgraph = "."                           # Output saved in current folder
+
+library(haven) 
+library(dplyr)
+library(pilot1wrappers)
+library(ggplot2)
+library(cowplot)
+library(visR)
+
+
+## -----------------------------------------------------------------------------------------------------------------------------------
+adsl <- read_xpt(file.path(path$adam, "adsl.xpt"))
+adtte <- read_xpt(file.path(path$adam, "adtte.xpt")) 
+
+
+## -----------------------------------------------------------------------------------------------------------------------------------
+anl <- adsl %>% 
+  dplyr::filter(
+    SAFFL == "Y",
+    STUDYID == "CDISCPILOT01"
+  ) %>%
+  dplyr::select(STUDYID, USUBJID, TRT01A) %>%
+  dplyr::inner_join(
+    filter(
+      adtte, PARAMCD == "TTDE", STUDYID == "CDISCPILOT01"
+    ) %>% select(STUDYID, USUBJID, AVAL, CNSR, PARAM, PARAMCD),
+    by = c("STUDYID", "USUBJID")
+  ) %>%
+  dplyr::mutate(
+    TRT01A = factor(TRT01A, levels = c("Placebo", "Xanomeline Low Dose",  "Xanomeline High Dose"))
+  )
+
+
+## -----------------------------------------------------------------------------------------------------------------------------------
+# estimate survival
+surv_mod <- visR::estimate_KM(data = anl, strata = "TRT01A")
+
+# save plot
+ggplot2::theme_set(theme_bw())
+
+pdf.options(reset = TRUE, onefile = FALSE)
+
+pdf(file.path(path$output, "tlf-kmplot.pdf"))
+
+KM <- visR::visr(surv_mod,
+           y_label = "Probability of event\n",
+           x_label = "Time to First Dermatologic Event (Days)",
+           y_ticks = seq(0,1,0.10)) %>%
+    add_CNSR() %>%
+    add_CI()
+
+KM <- KM + 
+    ggplot2::geom_hline(yintercept=0.5, linetype = "dashed")
+
+KM <- KM %>%
+    visR::add_risktable(group = "statlist")
+
+title <- cowplot::ggdraw() + 
+  cowplot::draw_label(
+    "KM plot for Time to First Dermatologic Event: Safety population\n",
+    fontfamily = "sans",
+    fontface = "bold",
+    size=10
+  ) 
+
+caption <- cowplot::ggdraw() + 
+  cowplot::draw_label(
+    paste0("\nProgram: tlf_kmplot.Rmd [", Sys.time(), "]"),
+    fontfamily = "sans",
+    size=10
+  ) 
+
+KM <- cowplot::plot_grid(
+  title, KM, caption,
+  ncol = 1,
+  rel_heights = c(0.1,0.8,0.1)
+)
+
+print(KM)
+dev.off()
+
+
+## ---- out.width = "100%", out.height = "400px", echo = FALSE, fig.align = "center"--------------------------------------------------
+knitr::include_graphics("pdf/tlf-kmplot.pdf")
+