Author: Brie Noble, Blake Langlais

# The toxAUC function

#### Brie Noble, Blake Langlais

# 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.

    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

    acute <- tox_acute

    str(acute)

    'data.frame':   1400 obs. of  7 variables:
     $ id             : int  1 1 1 1 1 1 1 1 1 1 ...
     $ Cycle          : int  1 2 3 4 5 6 7 8 9 10 ...
     $ arm            : chr  "Drug" "Drug" "Drug" "Drug" ...
     $ PROCTCAE_9A_SCL: num  0 2 4 0 0 0 0 0 0 0 ...
     $ PROCTCAE_9B_SCL: num  0 2 3 3 0 1 0 0 0 0 ...
     $ PROCTCAE_9_COMP: num  0 2 3 0 0 0 0 0 0 0 ...
     $ time           : chr  "Cycle 1" "Cycle 2" "Cycle 3" "Cycle 4" ...

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.

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

      index      short_label
    1     1 Nausea Frequency
    2     2  Nausea Severity
    3     3 Nausea Composite

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

    AUC[[3]][2]

[[1]]