Composite Plot for Visualizing Aminotransferase and Bilirubin Changes in Clinical Trials of Subjects with Abnormal Baseline Values

Bereket Tesfaldet ^1,2, Tejas Patel ³, Minjun Chen ⁴

⁰U.S. FDA, Center for Food Safety and Nutrition, Office of Analytics and Outreach, College Park, MD, USA. Bereket.tesfaldet@fda.hhs.gov.

Drug Safety +

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April 20, 2024

View abstract on PubMed

Summary

A new composite plot visualizes liver test changes during drug trials, comparing on-treatment results to upper limits of normal and baseline values. This tool aids in assessing drug safety and efficacy, especially in patients with pre-existing liver conditions.

Area Of Science

Clinical pharmacology
Hepatology
Biostatistics

Background

Assessing liver function tests (LFTs) during clinical trials is crucial for drug safety and efficacy, particularly in patients with liver disease.
Current visualization tools struggle to integrate on-treatment LFT excursions when baseline values are abnormal.

Purpose Of The Study

To develop a novel composite plot for visualizing on-treatment changes in LFTs.
The plot displays LFTs as multiples of the upper limit of normal (×ULN) and multiples of baseline values (×BLN).

Main Methods

The composite plot integrates biochemical evaluation for drug-induced severe hepatotoxicity (eDISH) with a four-panel shift plot.
It normalizes peak on-treatment LFTs by both ULN and individual subject baseline (BLN) values.

Main Results

The composite plot effectively visualizes improvements in LFTs during treatment compared to pre-treatment values.
It aids in identifying outlier subjects with potential drug-induced liver injury.

Conclusions

This composite plot offers a valuable tool for assessing liver test modifications in clinical trials, especially for subjects with abnormal baseline LFTs.
It facilitates the evaluation of both beneficial and concerning on-treatment changes relative to individual baselines and population thresholds.