---
title: "Visualization of clinical data"
author: "Laure Cougnaud, Michela Pasetto"
date: "`r format(Sys.Date(), '%B %d, %Y')`"
output: 
  rmarkdown::html_vignette:
    toc: true
    toc_depth: 5
    number_sections: true
vignette: >
  %\VignetteIndexEntry{Visualization of clinical data}
  %\VignetteEngine{knitr::rmarkdown}
  \usepackage[utf8]{inputenc}
---

```{r options, echo = FALSE, message = FALSE}

library(knitr)
opts_chunk$set(
    echo = TRUE, 
    results = 'asis', 
    warning = FALSE, 
    error = FALSE, message = FALSE, cache = FALSE,
    fig.width = 8, fig.height = 7,
    fig.path = "./figures_vignette/",
    fig.align = 'center')
```

This vignette focuses on the visualizations available in the 
`clinDataReview` package.

We will use example data sets from the `clinUtils` package.

If you have doubts on the data format, please check first the vignette on data
preprocessing available at:
[here](../doc/clinDataReview-dataPreprocessing.html).

If everything is clear on that side, let's get started!

Please note that the patient profiles and interactive
visualizations are only displayed in the vignette
if Pandoc is available.

```{r checkPandocAvailability, echo = FALSE}
hasPandoc <- rmarkdown::pandoc_available()
```

```{r loadLibraries}

library(clinDataReview)
library(plotly)

```

```{r loadData}	

library(clinUtils)

data(dataADaMCDISCP01)
labelVars <- attr(dataADaMCDISCP01, "labelVars")

varsLB <- c(
	"PARAM", "PARAMCD", "USUBJID", "TRTP", 
	"ADY", "VISITNUM", "VISIT", "LBSTRESN"
)
dataLB <- dataADaMCDISCP01$ADLBC[, varsLB]

varsAE <- c("USUBJID", "AESOC", "AEDECOD", "ASTDY", "AENDY", "AESEV")
dataAE <- dataADaMCDISCP01$ADAE[, varsAE]

varsDM <- c("RFSTDTC", "USUBJID")
dataDM <- dataADaMCDISCP01$ADSL[, varsDM]

```

# Patient profiles

**The interactive visualizations of the clinical data package include
functionalities to link a plot to patient-specific report**, e.g. patient
profiles created with the `patientProfilesVis` package.

Such patient profiles can be created via a config file, with a dedicated
template report available in the `clinDataReview` package.

A simple patient profile report for each subject in the example
dataset is created below.

Please note that the patient profiles are created and included in 
the interactive visualizations only during an interactive session
 (via `interactive()`) .

```{r patientProfilesCreate, results = "hide", eval = hasPandoc & interactive()}
# please change to the working directory
# (a temporary directory is used for the vignette)
dir <- tempdir()

# create a directory to store the patient profiles:
patientProfilesDir <- file.path(dir, "patientProfiles")
dir.create(patientProfilesDir)

# get examples of parameters for the report
configDir <- system.file("skeleton", "config", package = "clinDataReview")
params <- getParamsFromConfig(
	configDir = configDir, 
	configFile = "config-patientProfiles.yml"
)
# create patient profile with only one panel for the demo
params$patientProfilesParams <- params$patientProfilesParams[1]
# use dataset from the clinUtils package
params$pathDataFolder <- system.file("extdata", "cdiscpilot01", "SDTM", package = "clinUtils")
# store patient profile in this folder:
params$patientProfilePath <- patientProfilesDir

# create patient profiles
pathTemplatePkg <- clinDataReview::getPathTemplate(params$template)
pathTemplateUser <- file.path(dir, basename(pathTemplatePkg))
tmp <- file.copy(from = pathTemplatePkg, to = pathTemplateUser)
report <- rmarkdown::render(
  input = pathTemplateUser, 
  envir = new.env()
)

# clean-up
unlink(pathTemplateUser);unlink(report)
```

Please refer to the vignette about reporting for more details on how 
to set up a config file and use template reports available
in the package.

You can directly skip to reporting vignette, which is available [here](../doc/clinDataReview-reporting.html) 
or run in your console the command below.

```{r reportingVignette, eval = FALSE}

vignette("clinDataReview-reporting", "clinDataReview")

```

# Data visualization

All the visualizations available in the package are interactive.

## Visualization of individual profiles

Visualization of individual profiles is available via the function
**`scatterplotClinData`**.

### Explore the visualization data

To facilitate the exploration of the data, the underlying data
behind each visualization can be included as a table as well
below the plot by setting the parameter `table` to TRUE. 

Please note that this functionality is not demonstrated in this document
to ensure a lightweight vignette in the package.

### Link with patient profiles

Subject-specific report (e.g. patient profiles) can be linked to each
profile (**`pathVar`** parameter).

If the user clicks on the **'P' key while
hovering on the plot**, or **click on the specific subject in the attached
table, the specific patient profile is opened in a new window in the browser**.

### Spaghetti plot of time profile

```{r timeProfiles, eval = hasPandoc}

labParam <- "ALT"
dataPlot <- subset(dataLB, PARAMCD == labParam)

visitLab <- with(dataPlot, tapply(ADY, VISIT, median))
names(visitLab) <- sub("-", "\n", names(visitLab))

# link to patient profiles
if(interactive())
	dataPlot$patientProfilePath <- paste0(
	    "patientProfiles/subjectProfile-", 
	    sub("/", "-", dataPlot$USUBJID), ".pdf"
	)

scatterplotClinData(
    data = dataPlot, 
    xVar = "ADY",
    yVar = "LBSTRESN",
    aesPointVar = list(color = "TRTP", fill = "TRTP"),
    aesLineVar = list(group = "USUBJID", color = "TRTP"),
    linePars = list(size = 0.5, alpha = 0.7),
    hoverVars = c("USUBJID", "VISIT", "ADY", "LBSTRESN", "TRTP"),
    labelVars = labelVars,
    xPars = list(breaks = visitLab, labels = names(visitLab)),
    title = paste("Actual value of", 
        getLabelParamcd(
            paramcd = labParam, data = dataLB, paramcdVar = "PARAMCD", paramVar = "PARAM"
        )
    ),
    # include link to patient profiles:
    pathVar = if(interactive())	"patientProfilePath",
	subtitle = paste(
		"Profile plot by subject",
		"Points are positioned at relative day",
		"Visits are positioned based on median relative day across subjects.",
		sep = "\n"
	),
	verbose = TRUE,
    table = FALSE
)

```

### Scatterplot

```{r scatterplot, eval = hasPandoc}
# format data long -> wide format (one column per lab param)
dataPlot <- subset(dataLB, PARAMCD %in% c("ALT", "ALB"))
dataPlot <- stats::aggregate(
	LBSTRESN ~ USUBJID + VISIT + VISITNUM + PARAMCD, 
	data = dataPlot,
	FUN = mean
)
dataPlotWide <- stats::reshape(
	data = dataPlot,
	timevar = "PARAMCD", idvar = c("USUBJID", "VISIT", "VISITNUM"),
	direction = "wide"
)
colnames(dataPlotWide) <- sub("^LBSTRESN.", "", colnames(dataPlotWide))

# link to patient profiles
if(interactive())
	dataPlotWide$patientProfilePath <- paste0(
	    "patientProfiles/subjectProfile-", 
	    sub("/", "-", dataPlotWide$USUBJID), ".pdf"
	)

# scatterplot per visit
scatterplotClinData(
    data = dataPlotWide, 
    xVar = "ALT", yVar = "ALB",
    xLab = getLabelParamcd(
        paramcd = "ALT", data = dataLB, paramcdVar = "PARAMCD", paramVar = "PARAM"
    ),
    yLab = getLabelParamcd(
        paramcd = "ALB", data = dataLB, paramcdVar = "PARAMCD", paramVar = "PARAM"
    ),
    aesPointVar = list(color = "USUBJID", fill = "USUBJID"),
    facetPars = list(facets = ~ VISIT),
    labelVars = labelVars,
    pathVar = if(interactive())	"patientProfilePath",
    table = FALSE
)

```

### eDish plot

```{r eDishPlot, eval = hasPandoc}

dataALT <- subset(dataLB, PARAMCD == "ALT")
dataBILI <- subset(dataLB, PARAMCD == "BILI")

byVar <- c("USUBJID", "VISIT")

dataPlot <- merge(
    x = dataALT, y = dataBILI[, c(byVar, "LBSTRESN")], 
    by = c("USUBJID", "VISIT"), 
    suffixes = c(".ALT", ".BILI"),
    all = TRUE
)
labelVars[paste0("LBSTRESN.", c("ALT", "BILI"))] <-
    paste(
        "Actual value of", 
        getLabelParamcd(
            paramcd = c("ALT", "BILI"), data = dataLB, paramcdVar = "PARAMCD", paramVar = "PARAM"
        )
    )

# link to patient profiles
if(interactive())
	dataPlot$patientProfilePath <- paste0(
	    "patientProfiles/subjectProfile-", 
	    sub("/", "-", dataPlot$USUBJID), ".pdf"
	)

# scatterplot per visit
scatterplotClinData(
    data = dataPlot, 
    xVar = "LBSTRESN.ALT", yVar = "LBSTRESN.BILI",
    xLab = getLabelParamcd(
        paramcd = "ALT", data = dataLB, paramcdVar = "PARAMCD", paramVar = "PARAM"
    ),
    yLab = getLabelParamcd(
        paramcd = "BILI", data = dataLB, paramcdVar = "PARAMCD", paramVar = "PARAM"
    ),
    aesPointVar = list(color = "VISIT", fill = "VISIT"),
    xTrans = "log10", yTrans = "log10",
    hoverVars = "USUBJID",
    labelVars = labelVars,
    table = FALSE, 
    pathVar = if(interactive())	"patientProfilePath"
)

```

### Visualization of time-intervals

Time-intervals are displayed with the **`timeProfileIntervalPlot`** function:

```{r timeProfileIntervalPlot, eval = hasPandoc}

# link to patient profiles
if(interactive())
	dataAE$patientProfilePath <- paste0(
	    "patientProfiles/subjectProfile-", 
	    sub("/", "-", dataAE$USUBJID), ".pdf"
	)
timeProfileIntervalPlot(
    data = dataAE,
    paramVar = "USUBJID",
    # time-variables
    timeStartVar = "ASTDY",
    timeEndVar = "ASTDY",
    colorVar = "AESEV",
    hoverVars = c("USUBJID", "AEDECOD", "ASTDY", "AENDY", "AESEV"),
    labelVars = labelVars,
    table = FALSE, 
	pathVar = if(interactive())	"patientProfilePath",
    tableVars = c("USUBJID", "AEDECOD", "ASTDY", "AENDY", "AESEV")
)

```

By default, empty intervals are represented if the start/end time variables are
missing. Missing start/end time can be imputed, or different symbols can be used
to represent such cases:

```{r timeProfileIntervalPlot-shapeVariables, eval = hasPandoc}

# create variable to indicate status of start/end date
dataAE$AESTFLG <- ifelse(is.na(dataAE$ASTDY), "Missing start", "Complete")
dataAE$AEENFLG <- ifelse(is.na(dataAE$AENDY), "Missing end", "Complete")
shapePalette <- c(
    `Missing start` = "triangle-left", 
    `Complete` = "square-open", 
    `Missing end` = "triangle-right"
)

# 'simple'-imputation:
# if start is missing, 'Missing' symbol displayed at end interval
dataAE$AESTDYIMP <- with(dataAE, ifelse(is.na(ASTDY), AENDY, ASTDY))
# if end is missing, 'Missing' symbol displayed at start interval
dataAE$AEENDYIMP <- with(dataAE, ifelse(is.na(AENDY), ASTDY, AENDY))

timeProfileIntervalPlot(
    data = dataAE,
    paramVar = "USUBJID", 
    # time-variables
    timeStartVar = "AESTDYIMP", timeStartLab = "Start day",
    timeEndVar = "AEENDYIMP", timeEndLab = "End day",
    # shape variables
    timeStartShapeVar = "AESTFLG",
    timeStartShapeLab = "Status of start date",
    timeEndShapeVar = "AEENFLG",
    timeEndShapeLab = "Status of end date",
    shapePalette = shapePalette,
    hoverVars = c("USUBJID", "AEDECOD", "AESEV", "ASTDY", "AESTFLG", "AENDY", "AEENFLG"),
    labelVars = labelVars,
    table = FALSE, 
    tableVars = c("USUBJID", "AEDECOD", "AESEV", "ASTDY", "AESTFLG", "AENDY", "AEENFLG"),
    pathVar = if(interactive())	"patientProfilePath"
)

```

## Visualization of summary statistics

Summary statistics can also be visualized with the package, via different types
of visualizations: sunburst, treemap and barplot.

These functions take as input a table of summary statistics, especially counts.
Such table can e.g. computed with the `inTextSummaryTable` R package (see
corresponding package vignette for more information).

### Link with patient profiles

Subject-specific report (e.g. patient profiles) can be linked to each profile 
(**`pathVar`** parameter). If the user clicks on the **'P' key while hovering on
the plot, a zip file containing the reports for all corresponding patients is
downloaded**. If the attached table is display, each row can be extended to
display the links of the respective patient profile reports.

### Categorical variables

#### Compute count statistics

In this example, counts of adverse events are extracted for each
`r labelVars["AESOC"]` and `r labelVars["AEDECOD"]`.   

Besides the counts of the
number of subjects, the paths to the patient profile report for each subgroup
are extracted and combined.

```{r computeSummaryStatistics-categoricalVariable, eval = requireNamespace("inTextSummaryTable", quietly = TRUE)}

# total counts: Safety Analysis Set (patients with start date for the first treatment)
dataTotal <- subset(dataDM, RFSTDTC != "")

## patient profiles report

if(interactive()){

	# add path in data
	
	dataAE$patientProfilePath <- paste0(
	    "patientProfiles/subjectProfile-", 
	    sub("/", "-", dataAE$USUBJID), ".pdf"
	)

	# add link in data (for attached table)
	dataAE$patientProfileLink <- with(dataAE,
	    paste0(
	        '<a href="', patientProfilePath, 
	        '" target="_blank">', USUBJID, '</a>'
	    )
	)

	# Specify extra summarizations besides the standard stats
	# When the data is summarized,
	# the patient profile path are summarized
	# as well across patients
	# (the paths should be collapsed with: ', ')
	statsExtraPP <- list(
	    statPatientProfilePath = function(data)	
	      toString(sort(unique(data$patientProfilePath))),
	    statPatientProfileLink = function(data)
	      toString(sort(unique(data$patientProfileLink)))
	)
	
}

# get counts (records, subjects, % subjects) + stats with subjects profiles path
statsPP <- c(
	inTextSummaryTable::getStats(type = "count"),
    if(interactive())
		list(
        	patientProfilePath = quote(statPatientProfilePath),
        	patientProfileLink = quote(statPatientProfileLink)
    	)
)

dataAE$AESEV <- factor(
	dataAE$AESEV,
	levels = c("MILD", "MODERATE", "SEVERE")
)
dataAE$AESEVN <- as.numeric(dataAE$AESEV)

# compute adverse event table
tableAE <- inTextSummaryTable::computeSummaryStatisticsTable(
    
    data = dataAE,
    rowVar = c("AESOC", "AEDECOD"),
    dataTotal = dataTotal,
    labelVars = labelVars,
    
    # The total across the variable used for the nodes
	# should be specified
    rowVarTotalInclude = c("AESOC", "AEDECOD"),
	
	rowOrder = "total",
    
    # statistics of interest
    # include columns with patients
    stats = statsPP, 
    # add extra 'statistic': concatenate subject IDs
    statsExtra = if(interactive())	statsExtraPP

)
knitr::kable(head(tableAE),
    caption = paste("Extract of the Adverse Event summary table",
        "used for the sunburst and barplot visualization"
    )
)

```

#### Sunburst

The **`sunburstClinData`** function visualizes the counts of hierarchical data
in nested circles.

The different groups are visualized from the biggest class (root node) in the
center of the visualization to the smallest sub-groups (leaves) on the outside
of the circles.

The size of the different segments is relative the respective counts.

```{r sunburst, eval = hasPandoc & requireNamespace("inTextSummaryTable", quietly = TRUE)}

dataSunburst <- tableAE

dataSunburst$m <- as.numeric(dataSunburst$m)

sunburstClinData(
    data = dataSunburst,
    vars = c("AESOC", "AEDECOD"),
    valueVar = "m", 
	valueLab = "Number of adverse events",
    pathVar = if(interactive())	"patientProfileLink",
    pathLab = clinUtils::getLabelVar(var = "USUBJID", labelVars = labelVars),
    table = FALSE,
    labelVars = labelVars
)

```

#### Treemap

A treemap visualizes the counts of the hierarchical data in nested rectangles.
The area of each rectangle is proportional to the counts of the respective
group.

Note, that a treemap can also be colored accordingly to a meaningful
variable. For instance, if we show adverse events, we might **color the plot by
severity**. This can be achieved with the **colorVar** parameter.

```{r treemap, eval = hasPandoc & requireNamespace("inTextSummaryTable", quietly = TRUE)}

dataTreemap <- tableAE

dataTreemap$m <- as.numeric(dataTreemap$m)

treemapClinData(
    data = dataTreemap,
    vars = c("AESOC", "AEDECOD"),
    valueVar = "m",
    valueLab = "Number of adverse events",
    pathVar = if(interactive()) "patientProfileLink",
    pathLab = clinUtils::getLabelVar(var = "USUBJID", labelVars = labelVars),
    table = FALSE,
    labelVars = labelVars
)

```

#### Barplot

A barplot visualizes the counts for one single variable in a specific order.

```{r barplot, eval = hasPandoc & requireNamespace("inTextSummaryTable", quietly = TRUE)}

dataPlot <- subset(tableAE, AEDECOD != "Total")

dataPlot$n <- as.numeric(dataPlot$n)

# create plot
barplotClinData(
    data = dataPlot,
    xVar = "AEDECOD", 
    yVar = "n",
    yLab = "Number of patients with adverse events",
	textVar = "n",
    labelVars = labelVars,
    pathVar = if(interactive())	"patientProfileLink",
    pathLab = clinUtils::getLabelVar(var = "USUBJID", labelVars = labelVars),
    table = FALSE
)

```

### Continuous variable

```{r getData-continuousVariable}

dataVSDIABP <- subset(dataADaMCDISCP01$ADVS, 
	PARAMCD == "DIABP" & ANL01FL == "Y" &
	AVISIT %in% c("Baseline", "Week 2", "Week 4", "Week 6", "Week 8")
)

# add link to patient profiles report

# add path in data
if(interactive()){
	
	dataVSDIABP$patientProfilePath <- paste0(
		"patientProfiles/subjectProfile-", 
		sub("/", "-", dataVSDIABP$USUBJID), ".pdf"
	)

	# add link in data (for attached table)
	dataVSDIABP$patientProfileLink <- with(dataVSDIABP,
		paste0(
			'<a href="', patientProfilePath, 
			'" target="_blank">', USUBJID, '</a>'
		)
	)

}

```

#### Compute summary statistics

```{r computeSummaryStatistics-continuousVariable, eval = requireNamespace("inTextSummaryTable", quietly = TRUE)}

# Specify extra summarizations besides the standard stats
# When the data is summarized,
# the patient profile path are summarized
# as well across patients
# (the paths should be collapsed with: ', ')
if(interactive())
	statsExtraPP <- list(
	    statPatientProfilePath = function(data)	
	      toString(sort(unique(data$patientProfilePath))),
	    statPatientProfileLink = function(data)
	      toString(sort(unique(data$patientProfileLink)))
	)
	
# get default counts + stats with subjects profiles path
statsPP <- c(
    inTextSummaryTable::getStats(x = dataVSDIABP$AVAL, type = "summary"),
	if(interactive())
	    list(
	        patientProfilePath = quote(statPatientProfilePath),
	        patientProfileLink = quote(statPatientProfileLink)
	    )
)

# compute summary table of actual value
summaryTableCont <- inTextSummaryTable::computeSummaryStatisticsTable(
    
    data = dataVSDIABP,
    rowVar = c("AVISIT", "ATPT"),
	var = "AVAL",
	
    labelVars = labelVars,
	
    # statistics of interest
    # for DT output, include columns with patients
    stats = statsPP, 
    # add extra 'statistic': concatenate subject IDs
    statsExtra = if(interactive())	statsExtraPP

)
knitr::kable(head(summaryTableCont, 1))
```

#### Plot error bars/confidence intervals

```{r errorbarClinData, eval = hasPandoc & requireNamespace("inTextSummaryTable", quietly = TRUE)}

dataPlot <- subset(summaryTableCont, !isTotal)

errorbarClinData(
	data = dataPlot,
	xVar = "AVISIT",
	colorVar = "ATPT",
	
	# use non-rounded statistics for the plot
	yVar = "statMean", 
	yErrorVar = "statSE", 
	
	# display rounded stats in the hover + n: number of subjects
	hoverVars = c("AVISIT", "ATPT", "n", "Mean", "SE"),
	
	yLab = "Mean", yErrorLab = "Standard Error",
	title = "Diastolic Blood Pressure summary profile by actual visit and and analysis timepoint",
	
	# include lines connecting the error bars
	mode = "markers+lines", 
	
	table = FALSE, labelVars = labelVars,
	pathVar = if(interactive())	"patientProfileLink",
	pathLab = clinUtils::getLabelVar(var = "USUBJID", labelVars = labelVars)

)

```

#### Boxplot

A boxplot visualizes the distribution of a continuous variable of interest
versus specific categorical variables.

This visualization doesn't rely on pre-computed statistics, so
the continuous variable of interest is directly passed to
the functionality.

```{r boxplot, eval = hasPandoc}

dataPlot <- subset(dataADaMCDISCP01$ADVS, 
	PARAMCD == "DIABP" & ANL01FL == "Y" &
	AVISIT %in% c("Baseline", "Week 2", "Week 4", "Week 6", "Week 8")
)

# link to patient profiles
if(interactive())
	dataPlot$patientProfilePath <- paste0(
		"patientProfiles/subjectProfile-", 
		sub("/", "-", dataPlot$USUBJID), ".pdf"
	)

boxplotClinData(
	data = dataPlot,
	xVar = "AVISIT", 
	yVar = "AVAL",
	colorVar = "TRTA",
	facetVar = "ATPT",
	title = "Diastolic Blood Pressure distribution by actual visit and analysis timepoint",
	yLab = "Actual value of the Diastolic Blood Pressure parameter (mmHg)",
	labelVars = labelVars,
	pathVar = if(interactive())	"patientProfilePath",
	pathLab = clinUtils::getLabelVar(var = "USUBJID", labelVars = labelVars),
	table = FALSE
)

```

## Multiple visualizations in a loop

To include multiple clinical data visualizations (with or without attached
table) in a loop (in the same _Rmarkdown_ chunk), the list of visualizations
should be passed to the `knitPrintListObjects` function of the `clinUtils`
package.

```{r lab-profile-loop, results = "asis", eval = hasPandoc}

# consider only restricted set of lab parameters
dataPlot <- subset(dataLB, PARAMCD %in% c("SODIUM", "K"))

# link to patient profiles
if(interactive())
	dataPlot$patientProfilePath <- paste0(
	    "patientProfiles/subjectProfile-", 
	    sub("/", "-", dataPlot$USUBJID), ".pdf"
	)

# 1) create plot+table for each laboratory parameter:
library(plyr) # for ddply
plotsLab <- dlply(dataPlot, "PARAMCD", function(dataLBParam){
      
      paramcd <- unique(dataLBParam$PARAMCD)
      
      scatterplotClinData(
          data = dataLBParam, 
          xVar = "ADY",
          yVar = "LBSTRESN",
          aesPointVar = list(color = "TRTP", fill = "TRTP"),
          aesLineVar = list(group = "USUBJID", color = "TRTP"),
          labelVars = labelVars,
          title = paste("Actual value of", 
              getLabelParamcd(
                  paramcd = paramcd, data = dataLBParam, paramcdVar = "PARAMCD", paramVar = "PARAM"
              )
          ),
          # include link to patient profiles:
          pathVar = if(interactive())	"patientProfilePath",
          table = FALSE, 
          # important: each plot should have an unique ID!
          # for unique relationship of interactivity between plot <-> table
          id = paste("labProfileLoop", paramcd, sep = "-")
      )
      
    })

# include this output in the report:
listLabels <- getLabelParamcd(
    paramcd = names(plotsLab), data = dataLB, paramcdVar = "PARAMCD", paramVar = "PARAM"
)
clinUtils::knitPrintListObjects(
    xList = plotsLab, 
    titles = listLabels, titleLevel = 4
)

```

## Watermark

A watermark can be included in any of the visualization of the package, from a specified file, via the `watermark` parameter.  

In this example, an exploratory watermark is added to the adverse events barplot.

```{r watermark, eval = requireNamespace("inTextSummaryTable", quietly = TRUE)}
# create a file with a 'EXPLORATORY' watermark
file <- tempfile(pattern = "watermark", fileext = ".png")
getWatermark(file = file)

# create plot
barplotClinData(
  data = subset(tableAE, AEDECOD != "Total"),
  xVar = "AEDECOD", 
  yVar = "n",
  yLab = "Number of patients with adverse events",
  textVar = "n",
  labelVars = labelVars,
  # include the watermark
  watermark = file,
  table = FALSE
)
```

# Palettes

## Set palette for the entire session

Palette for the colors and shapes associated with specific variables can be set
for all clinical data visualizations at once by setting the
`clinDataReview.colors` and `clinDataReview.shapes` options at the start
of the R session.

Please see the `clinUtils` package for the default colors and shapes.

```{r palettes-default-get, results = 'markup'}

# display default palettes
colorsDefault <- getOption("clinDataReview.colors")
str(colorsDefault)
shapesDefault <- getOption("clinDataReview.shapes")
str(shapesDefault)

```

```{r palettes-default-example, eval = hasPandoc}

timeProfileIntervalPlot(
    data = dataAE,
    paramVar = "USUBJID",
    # time-variables
    timeStartVar = "ASTDY",
    timeEndVar = "AENDY",
    colorVar = "AESEV",
    timeStartShapeVar = "AESTFLG",
    timeEndShapeVar = "AEENFLG",
    labelVars = labelVars
)

```

The palettes can be set for all visualizations, e.g. at the start of the R
session, with:

```{r palettes-customGeneral-set}
# change palettes for the entire R session
options(clinDataReview.colors = c("gold", "pink", "cyan"))
options(clinDataReview.shapes = clinShapes)
```

In case the palette contains less elements than available in the data, these are
replicated.

```{r palettes-customGeneral-example, eval = hasPandoc}

timeProfileIntervalPlot(
    data = dataAE,
    paramVar = "USUBJID",
    # time-variables
    timeStartVar = "ASTDY",
    timeEndVar = "AENDY",
    colorVar = "AESEV",
    timeStartShapeVar = "AESTFLG",
    timeEndShapeVar = "AEENFLG",
    labelVars = labelVars
)

```

Palettes are reset to the default patient profiles palettes at the start of a
new R session, or by setting:

```{r palettes-default-reset}

# change palettes for the entire R session
options(clinDataReview.colors = colorsDefault)
options(clinDataReview.shapes = shapesDefault)

```

# Appendix

## Session info

```{r sessionInfo, echo = FALSE}

print(sessionInfo())

```

