Evidence map›Paper›PMID 31328865›Full record

ArticleClinical and translational science2019

Clinical Trial in a Dish: Personalized Stem Cell-Derived Cardiomyocyte Assay Compared With Clinical Trial Results for Two QT-Prolonging Drugs.

Ksenia Blinova, Derek Schocken, Dakshesh Patel, Chathuri Daluwatte, Jose Vicente, Joseph C Wu, David G Strauss

Open access · goldAbstract readClinical Trial, Phase IComparative Study
In one paragraph

Article in Clinical and translational science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 10% 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

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Single-cell ionic current phenotyping explains stem cell-derived cardiomyocyte action potential morphology.American journal of physiology. Heart and circulatory physiology · 2024
    Article
  15. Toward Digital Twin Technology for Precision Pharmacology.JACC. Clinical electrophysiology · 2024
    Review
  16. Article
  17. Review
  18. Article
  19. Leak current, even with gigaohm seals, can cause misinterpretation of stem cell-derived cardiomyocyte action potential recordings.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2023
    Article
  20. 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

7 authors at 5 institutions in 1 country.

Ksenia BlinovaCenter for Devices and Radiological Health, Office of Science and Engineering Laboratories, US Food and Drug Administration, Silver Spring, Maryland, USA.
Derek SchockenCenter for Devices and Radiological Health, Office of Science and Engineering Laboratories, US Food and Drug Administration, Silver Spring, Maryland, USA.
Dakshesh PatelCenter for Devices and Radiological Health, Office of Science and Engineering Laboratories, US Food and Drug Administration, Silver Spring, Maryland, USA.
Chathuri DaluwatteCenter for Drug Evaluation and Research, Office of Clinical Pharmacology, US Food and Drug Administration, Silver Spring, Maryland, USA.
Jose VicenteCenter for Drug Evaluation and Research, Office of New Drugs, US Food and Drug Administration, Silver Spring, Maryland, USA.
Joseph C WuStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA.
David G StraussCenter for Drug Evaluation and Research, Office of Clinical Pharmacology, US Food and Drug Administration, Silver Spring, Maryland, USA.
Office of Science · USUnited States Food and Drug Administration · USCenter for Devices and Radiological Health · USCenter for Drug Evaluation and Research · USStanford University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Induced pluripotent stem cells (iPSCs) have shown promise in investigating donor-specific phenotypes and pathologies. The iPSC-derived cardiomyocytes (iPSC-CMs) could potentially be utilized in personalized cardiotoxicity studies, assessing individual proarrhythmic risk. However, it is unclear how closely iPSC-CMs derived from healthy subjects can recapitulate a range of responses to drugs. It is well known that QT-prolonging drugs induce subject-specific clinical response and that all healthy subjects do not necessarily develop arrhythmias or exhibit similar amounts of QT prolongation. We previously reported this variability in a study of four human ether-a-go-go-related gene (hERG) potassium channel-blocking drugs in which each subject underwent intensive pharmacokinetic and pharmacodynamic sampling such that subjects had 15 time-matched plasma drug concentration and electrocardiogram measurements throughout 24 hours after dosing in a phase I clinical research unit. In this study, iPSC-CMs were generated from those subjects. Their drug-concentration-dependent QT prolongation response from the clinic was compared with in vitro drug-concentration-dependent action potential duration (APD) prolongation response to the same two hERG-blocking drugs, dofetilide and moxifloxacin. Comparative results showed no significant correlation between the subject-specific APD response slopes and clinical QT response slopes to either moxifloxacin (P = 0.75) or dofetilide (P = 0.69). Similarly, no significant correlation was found between baseline QT and baseline APD measurements (P = 0.93). This result advances our current understanding of subject-specific iPSC-CMs and facilitates discussion into factors obscuring correlation and considerations for future studies of subject-specific phenotypes in iPSC-CMs.

Indexed as

Primary Cell CultureAction PotentialsAdultCardiotoxicityCell DifferentiationCells, CulturedCross-Over StudiesDose-Response Relationship, DrugElectrocardiographyFemaleHumansInduced Pluripotent Stem CellsLong QT SyndromeMaleMoxifloxacinMyocytes, CardiacdofetilideMoxifloxacinPhenethylaminesSulfonamides

Identifiers

PMID31328865
PMCPMC6853144
OpenAlexW2964172723

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.