Evidence map›Paper›PMID 38642292›Full record

ArticleDrug safety2024

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

Bereket Tesfaldet, Tejas Patel, Minjun Chen, Frank Pucino, Lilliam Rosario, Paul Hayashi, Eileen Navarro Almario

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Drug safety, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Bereket TesfaldetU.S. FDA, Center for Food Safety and Nutrition, Office of Analytics and Outreach, College Park, MD, USA. Bereket.tesfaldet@fda.hhs.gov.ORCID http://orcid.org/0000-0001-7642-0755
Tejas PatelU.S. FDA, Center for Drug Evaluation and Research, Office of New Drugs, Silver Spring, MD, USA.
Minjun ChenU.S. FDA, Office of the Chief Scientist, National Center for Toxicology Research, Division of Bioinformatics and Biostatistics, Jefferson, AR, USA.
Frank PucinoU.S. FDA, Center for Drug Evaluation and Research, Office of New Drugs, Silver Spring, MD, USA.
Lilliam RosarioU.S. FDA, Center for Drug Evaluation and Research, Office of Translational Sciences, Office of Computational Science, Silver Spring, MD, USA.
Paul HayashiU.S. FDA, Center for Drug Evaluation and Research, Office of New Drugs, Silver Spring, MD, USA.
Eileen Navarro AlmarioU.S. FDA, Center for Drug Evaluation and Research, Office of New Drugs, Silver Spring, MD, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionOn-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.

objectiveThe 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.

methodsThe 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.

resultsThe 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.

conclusionFor 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.

Indexed as

BilirubinChemical and Drug Induced Liver InjuryLiver Function TestsClinical Trials as TopicHumansTransaminasesBilirubinTransaminases

Identifiers

PMID38642292
PMCPMC11182847

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.