Evidence map›Paper›PMID 30257217›Full record

ArticleCell reports2018

International Multisite Study of Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Drug Proarrhythmic Potential Assessment.

Ksenia Blinova, Qianyu Dang, Daniel Millard, Godfrey Smith, Jennifer Pierson, Liang Guo, Mathew Brock, Hua Rong Lu, Udo Kraushaar, Haoyu Zeng and 12 more

Abstract readMulticenter StudyValidation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 197 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
197citing papers in PubMed, 2 pooled it
–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

197 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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137 more citing papers are in PubMed but not listed here.

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

22 authors.

Ksenia BlinovaDivision of Biomedical Physics, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, MD 20993, USA. Electronic address: ksenia.blinova@fda.hhs.gov.
Qianyu DangOffice of Biostatistics, Office of Translational Science, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 20993, USA.
Daniel MillardAxion BioSystems, Atlanta, GA 30309, USA.
Godfrey SmithUniversity of Glasgow, Glasgow G12 8QQ, Scotland, UK; Clyde Biosciences, Newhouse ML1 5UH, Scotland, UK.
Jennifer PiersonHealth and Environmental Sciences Institute, Washington, DC 20005, USA.
Liang GuoInvestigative Toxicology, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Frederick, MD 21702, USA.
Mathew BrockGenentech, San Francisco, CA 94080, USA.
Hua Rong LuDiscovery Sciences, R&D, Janssen Pharmaceutical (JNJ), Beerse, Belgium.
Udo KraushaarNMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany.
Haoyu ZengMerck, Safety & Exploratory Pharmacology Department, West Point, PA 19486, USA.
Hong ShiBristol-Myers Squibb, New York, NY 10154, USA.
Xiaoyu ZhangACEA Biosciences, San Diego, CA 92121, USA.
Kohei SawadaEisai, Tsukuba, Ibaraki 300-2635, Japan; The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Tomoharu OsadaLSI Medience, Chiyoda-ku, Tokyo 101-8517, Japan.
Yasunari KandaDivision of Pharmacology, National Institute of Health Sciences, Kawasaki, Kanagawa 210-9501, Japan.
Yuko SekinoThe University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan; Division of Pharmacology, National Institute of Health Sciences, Kawasaki, Kanagawa 210-9501, Japan.
Li PangDivision of Biochemical Toxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA.
Tromondae K FeasterCellular Dynamics International-A FUJIFILM Company, Madison, WI 53711, USA.
Ralf KettenhofenNcardia, Cologne 50829, Germany.
Norman StockbridgeDivision of Cardiovascular and Renal Products, Office of Drug Evaluation I, Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 20993, USA.
David G StraussDivision of Applied and Regulatory Science, Office of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 20993, USA.
Gary GintantAbbVie, North Chicago, IL 60064-6118, USA. Electronic address: gary.gintant@abbvie.com.

Funding

CCR NIH HHS HHSN261200800001CIntramural FDA HHS FD999999NCI NIH HHS HHSN261200800001E
6 · The paper itself

Abstract

To assess the utility of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as an in vitro proarrhythmia model, we evaluated the concentration dependence and sources of variability of electrophysiologic responses to 28 drugs linked to low, intermediate, and high torsades de pointes (TdP) risk categories using two commercial cell lines and standardized protocols in a blinded multisite study using multielectrode array or voltage-sensing optical approaches. Logistical and ordinal linear regression models were constructed using drug responses as predictors and TdP risk categories as outcomes. Three of seven predictors (drug-induced arrhythmia-like events and prolongation of repolarization at either maximum tested or maximal clinical exposures) categorized drugs with reasonable accuracy (area under the curve values of receiver operator curves ∼0.8). hiPSC-CM line, test site, and platform had minimal influence on drug categorization. These results demonstrate the utility of hiPSC-CMs to detect drug-induced proarrhythmic effects as part of the evolving Comprehensive In Vitro Proarrhythmia Assay paradigm.

Indexed as

CardiotoxicityCell LineCellular ReprogrammingDrug Evaluation, PreclinicalElectrophysiologyHumansInduced Pluripotent Stem CellsMembrane PotentialsMyocytes, CardiacTorsades de PointesCiPAcomprehensive in vitro proarrhythmia assaydrug-induced ventricular arrhythmia Torsade de PointeshiPSC-CMhuman-induced pluripotent stem cell-derived cardiomycotesmicroelectrode arrayvoltage-sensitive dyes

Identifiers

PMID30257217
PMCPMC6226030

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.