---
title: "The toxAUC function"
author: "Brie Noble, Blake Langlais"
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```{r include=FALSE}

knitr::opts_chunk$set(eval = TRUE, message = FALSE, results = 'asis', comment='')
options(width = 200)

```

# Introduction

The `toxAUC()` function gives the user a set of tools to assess incremental AUC (iAUC) adjusted for baseline symptoms. The accumulated area of the symptomatic AE profile above baseline can be interpreted as symptom worsening driven by treatment. Arm-level iAUCs can be compared statistically using the function parameters. 

```{r,load-data}
library(ProAE)
require(knitr)

data(tox_acute)

```


In the example below, we will use the provided `ProAE::tox_acute` data
frame. This data was simulated to demonstrate a common symptomatic AE
profile where the drug group experiences acute toxicity followed by
symptom abatement over the course of treatment.

In order to use the `toxAUC()` function the data frame needs to be in
long format (multiple rows per patient). Additionally, the cycle
variable needs to be numeric. 


# Example 1 - Calculate and compare baseline adjusted incremental area under the curve by arm

```{r, results='markup'}

acute <- tox_acute

str(acute)
  
```

Below is the call for the `toxAUC()` function which will graph the the iAUC above baseline for two arms over the course of the trial. It will also perform a permutation test and provide a two-sided p value comparing the iAUC between the two arms.

```{r,warnings=FALSE,results='markup'}

AUC = toxAUC(dsn = acute,
             id_var = "id",
             cycle_var = "Cycle",
             arm_var = "arm",
             baseline_val = 1,
             permute_tests = TRUE)


```

Using the specified index from the table we can examine the table for the composite
score for Nausea

```{r fig.width=9,fig.height=4}

AUC[[3]][2]

```