Visualizing adverse events in clinical trials using correspondence analysis with R-package visae

TL;DR

This paper introduces a novel application of correspondence analysis with contribution biplots, implemented in an R-package, to visualize and explore adverse event data in clinical trials, enhancing interpretability and detection of treatment differences.

Contribution

The paper develops a new method using stacked correspondence analysis with contribution biplots and an interactive R Shiny app for analyzing adverse events in clinical trials.

Findings

Identified treatment differences and interaction effects in AE data.

Visualized patterns of adverse events across treatment groups.

Demonstrated the method on two large RCT datasets.

Abstract

We propose to apply stacked CA using contribution biplots as a tool to explore differences in AE data among treatments in clinical trials. We defined five levels of refinement for the analysis based on data derived from the Common Terminology Criteria for Adverse Events (CTCAE) grades, domains, terms and their combinations. In addition, we developed a Shiny app built in an R-package, publicly available on Comprehensive R Archive Network (CRAN), to interactively investigate CA configurations. Data from two randomized controlled trials (RCT) were used to illustrate the proposed methods: NSABP R-04, a neoadjuvant rectal 2x2 factorial trial comparing radiation therapy with either capecitabine (Cape) or 5-fluorouracil (5-FU) alone with or without oxaliplatin (Oxa), and NSABP B-35, a double-blind RCT comparing tamoxifen to anastrozole in postmenopausal women with hormone-positive ductal carcinoma in situ. In the R04 trial (n=1308), CA biplots displayed the discrepancies between single agent treatments and their combinations with Oxa at all levels of AE classes, such that these discrepancies were responsible for the largest portion of the explained variability among treatments. In addition, an interaction effect when adding Oxa to Cape/5-FU was identified when the distance between Cape+Oxa and 5-FU+Oxa was observed to be larger than the distance between 5-FU and Cape, with Cape+Oxa and 5-FU+Oxa in different quadrants of the CA biplots. In the B35 trial (n=3009), CA biplots showed different patterns for non-adherent Anastrozole and Tamoxifen compared with their adherent counterparts. CA with contribution biplot is an effective tool that can be used to summarize AE data in a two-dimensional display while minimizing the loss of information and interpretation.