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

Overview

Journal Drug Saf

Specialties Pharmacology
Toxicology

Date 2024 Apr 20

PMID 38642292

Authors

Bereket Tesfaldet

Tejas Patel

Minjun Chen

Frank Pucino

Lilliam Rosario

Paul Hayashi

Eileen Navarro Almario

Affiliations

Soon will be listed here.

Abstract

Introduction: On-treatment excursions of liver laboratory test values in clinical trials involving subjects with underlying liver disease are relevant for the efficacy and safety assessment of drug products and biologics. Existing visualization and analysis tools do not efficiently provide an integrated view of these excursions when baseline liver tests are abnormal.

Objective: The aim of this study was to develop a composite plot that enables visualization of on-treatment changes in liver test results both as multiples of the upper limit of normal defined by each laboratory's reference population (×ULN) and multiples of the subjects' baseline (×BLN) values.

Methods: The composite plot approach combines biochemical evaluation for drug-induced severe hepatotoxicity (eDISH) plots sequentially applied to subjects' baseline and peak on-treatment liver test results normalized by ULN and integrates them into a four-panel shift plot of peak on-treatment values normalized by BLN.

Results: The composite plot enabled efficient assessment of improvement in liver test values during treatment compared with pretreatment in subjects treated with the investigational drug (or the natural history of placebo-treated subjects) and identified outlier subjects for potential drug-induced liver injury.

Conclusion: For studies in subjects with abnormal baseline values, the composite plot has potential application in the assessment of beneficial and concerning on-treatment modifications in liver test values in reference to the individual subject's baseline and population threshold values.

Citing Articles

Emerging Tools to Support DILI Assessment in Clinical Trials with Abnormal Baseline Serum Liver Tests or Pre-existing Liver Diseases.

Amirzadegan J, Tesfaldet B, Pei Y, Navarro Almario E, Avigan M, Hayashi P Drug Saf. 2025; .

PMID: 39932652 DOI: 10.1007/s40264-024-01511-8.

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