Evidence map›Paper›PMID 36922938›Full record

ArticleCancer research communications2022

An Informatics Bridge to Improve the Design and Efficiency of Phase I Clinical Trials for Anticancer Drug Combinations.

Lei Wang, Lai Wei, Shijun Zhang, Lijun Cheng, Aditi Shendre, Williams Carson, James L Chen, Dwight Owen, Megan Gregory, Lang Li

Open access · goldFull text read
In one paragraph

Article in Cancer research communications, 2022. 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, top 91% of its field
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, 0 citations in OpenAlex.

  1. Article
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

10 authors at 2 institutions in 1 country.

Lei Wang *Department of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, Ohio.
Lai Wei *Department of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, Ohio.ORCID 0000-0002-7248-3828
Shijun ZhangDepartment of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, Ohio.
Lijun ChengDepartment of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, Ohio.
Aditi ShendreDepartment of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, Ohio.
Williams CarsonDivision of Surgical Oncology, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.
James L ChenDepartment of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, Ohio.
Dwight OwenDivision of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.ORCID 0000-0002-6598-4886
Megan GregoryDepartment of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, Ohio.
Lang LiDepartment of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, Ohio.ORCID 0000-0002-0746-1809
The Ohio State University · USThe Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute · US

Funding

The Indiana University-Ohio State University Maternal and Pediatric Precision in Therapeutics Data, Model, Knowledge, and Research Coordination Center (IU-OSU MPRINT DMKRCC)P30HD106451 · NICHD · INDIANA UNIVERSITY INDIANAPOLIS · PI Lang Li, Sara K Quinney · 2021 to 2026
$24.1M
Machine learning drives translational research from drug interactions to pharmacogeneticsR01LM014199 · NLM · OHIO STATE UNIVERSITY · PI You Chen, Lang Li · 2023 to 2026
$2.5M
Evidence-based Drug-Interaction Discovery: In-Vivo, In-Vitro and ClinicalR01LM011945 · NLM · INDIANA UNIVERSITY INDIANAPOLIS · PI LI, LANG, ROCHA, LUIS M · 2014 to 2017
$1.8M
An informatics bridge over the valley of death for cancer Phase I trials of drug-combination therapiesU01CA248240 · NCI · OHIO STATE UNIVERSITY · PI LI, LANG · 2021 to 2023
$1.1M
NCI NIH HHS U01 CA248240NICHD NIH HHS P30 HD106451NLM NIH HHS R01 LM011945NLM NIH HHS R01 LM014199
6 · The paper itself

Abstract

In this study, we summarized critical databases of drug combination toxicity and pharmacokinetics. We further conducted a feasibility and utility study that demonstrates how different data sources can contribute to and assist phase I trial designs. Single-drug and drug combination toxicity and pharmacokinetic data were primarily reviewed from several databases. We focused on the MTD, dose-limiting toxicity (DLT), toxicity, and pharmacokinetic profiles. To demonstrate the feasibility and utility of these data sources in improving trial designs, phase I studies reported in ClincalTrials.gov from January 1, 2018 to December 31, 2018 were used as examples. We evaluated whether and how these studies could have been designed differently given toxicity and pharmacokinetic data. None of the existing pharmacokinetic and toxicity databases contain either MTD or DLT. Among 268 candidate trials, four drug combinations were studied in other phase I trials before 2018; 185 combinations had complete or partial information on drug interactions or overlapping toxicity, and 79 combinations did not have available information. Two drug combination trials were selected as case studies. The nivolumab-axitinib trial could have been designed as a dose deescalating study, and the vinorelbine-trastuzumab emtansine trial could have been designed with a lower dose of either drug. Public data sources contain significant knowledge of the drug combination phase I trial design. Some important data (MTD and DLT) are not available in existing databases but in the literature. Some phase I studies could have been designed more efficiently with additional preliminary data. Significance: Prior preclinical and clinical knowledge is critical for designing effective and efficient cancer drug combinatory trials. We reported results on the feasibility and utility of different informatics resources for contributing to and assisting phase I trial designs based on our designed classification approach. We also found that public data sources contained significant knowledge for drug combination phase I trial design, but some critical data elements (MTD and DLT) were missing.

Indexed as

Antineoplastic AgentsClinical Trials, Phase I as TopicAntineoplastic Combined Chemotherapy ProtocolsVinorelbineAntineoplastic AgentsVinorelbine

Identifiers

PMID36922938
PMCPMC10010310
OpenAlexW4292401729

What OpenQuestion holds

Textfull text, public
LicenceCC BY
measurements read25
identifiers read3
Read underepoch 390

Registered trials

None linked

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.