PRO-CTCAE Scoring, Analysis, and Graphical Tools.

The ProAE Package

Overview

library(proae) is a collection of functions to facilitate standardized analysis and graphical procedures when using the National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

To use the functions, data needs to be long (multiple observations per patient (e.g one line per cycle) and one column per PRO-CTCAE item). Additionally, PRO-CTCAE items need to follow specific naming structure. PRO-CTCAE variable names are made up of FOUR components: 1)’PROCTCAE’, 2) number [1,2,3, ..., i, ..., 80], 3) ’A’, ’B’, or ’C’ component of the i-th PRO-CTCAE field, 4) and ’SCL’ (if severity, interference, or frequency) or ’IND’ (if yes/no variable). Each component must be delimited with an underscore (_).

ProAE::PROCTCAE_table provides a crosswalk/look-up table of expected variable names for associated PRO-CTCAE symptom items.

PRO-CTCAE Reference: https://healthcaredelivery.cancer.gov/pro-ctcae/instrument-pro.html

The toxScores() Function

toxScores() is a function that easiliy reformats PRO-CTCAE items that were collected as text responses to numeric, applies zero-imputation procedures, and constructs PRO-CTCAE composite grades. This function accepts 1 or up to all 124 PRO-CTCAE items. This function returns a data frame with the respective numerical re-coding and computations. This function should be used prior to other functions in this package.

Composite grading reference: https://pubmed.ncbi.nlm.nih.gov/33258687/

The toxFigures Function

toxFigures() is a function that creates publication quality longitudinal bar charts of symptomatic AE profiles. Frequency distributions of PRO-CTCAE scores can be shown over the course of the trial and can be stratified by treatment arm. An R list object is returned with the available PRO-CTCAE items indexed as elements of the list beside a reference table. See toxFigures vignette for more detail about how to customize these figures extensively using function parameters.

The toxTables() Function

toxTables() is a function that will produce PRO-CTCAE tables similar to those typically created for CTCAE data. These tables show arm-level sample size and frequency distributions for PRO-CTCAE items. P-values for statistical comparisons using chi-squared or Fisher's exact tests can be calculated as well as risk-difference between arms and alpha specified confidence intervals. See the toxTables() vignette for more details about how to use this function.

The toxSummary() Function

toxSummary() is a function that creates patient-level adjusted scores and group-level summary statistics. When requesting patient-level summary measures, the output is a data frame object with one observation per patient and include the id_var and PRO-CTCAE items are replaced with the adjusted score.

summary_measure options are:

• max - patient-level - the maximum score over the treatment period for each item

• max_post_bl - patient-level - the maximum score of all of the post-baseline timepoints for each item

• bl_adjusted - patient-level - the maximum score post-baseline if the maximum score is more severe than baseline. If the baseline score is equivalent or more severe than all post-baseline scores then zero (0) is used as the adjusted score

• toxicity_index - patient-level - the toxicity index for each patient. Reference: https://pubmed.ncbi.nlm.nih.gov/34371138/

• AUC_worsening' - group-level - For each level of the arm_var` or the entire sample, it calculates the modified Area Under the Curve (AUC) where PRO-CTCAE scores are worsening from baseline

• AUC_improvement' - group-level - For each level of the arm_var` or the entire sample, it calculates the modified Area Under the Curve (AUC) where PRO-CTCAE scores are improvement from baseline

The toxAUC() Function

toxAUC() is function that summarizes patient's symptomatic experience by calculating incremental AUC adjusted for baseline symptoms. Arm-level AUCs can be compared statistically using function parameters. See the toxAUC() vignette for more details about how to use this function.

Other objects

ProAE also includes simulated data of common symptomatic AE profiles such as acute, cumulative, cyclical, and late toxicity at various effect sizes for power or exploratory analysis.

• tox_acute is a simulated data frame where the drug group experiences acute toxicity followed by symptom abatement over the course of treatment.

• tox_chronic is simulated data frame where the drug group experiences chronic toxicity over the course of treatment.

• tox_cummulative is a simulated data frame where drug toxicity is cumulative over the course of treatment.

• tox_late is a simulated data frame where the drug group experiences late incipient toxicity towards the end of the treatment period.