ArticleClinical pharmacology and therapeutics2019
Thorough QT/QTc in a Dish: An In Vitro Human Model That Accurately Predicts Clinical Concentration-QTc Relationships.
Article in Clinical pharmacology and therapeutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
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- Incorporating new approach methods (NAMs) data in dose-response assessments: The future is now!Journal of toxicology and environmental health. Part B, Critical reviews · 2025Review
- Clinical trials in-a-dish for cardiovascular medicine.European heart journal · 2024Review
- Characterizing PFAS hazards and risks: a human population-based in vitro cardiotoxicity assessment strategy.Human genomics · 2024Article
- Informing Hazard Identification and Risk Characterization of Environmental Chemicals by Combining Transcriptomic and Functional Data from Human-Induced Pluripotent Stem-Cell-Derived Cardiomyocytes.Chemical research in toxicology · 2024Article
- Predicting oncology drug-induced cardiotoxicity with donor-specific iPSC-CMs-a proof-of-concept study with doxorubicin.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Evaluating scientific confidence in the concordance of in vitro and in vivo protective points of departure.Regulatory toxicology and pharmacology : RTP · 2024Article
- Article
- Beyond pharmaceuticals: Fit-for-purpose new approach methodologies for environmental cardiotoxicity testing.ALTEX · 2023Review
- Decision-Making with New Approach Methodologies: Time to Replace Default Uncertainty Factors with Data.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Integrating nonlinear analysis and machine learning for human induced pluripotent stem cell-based drug cardiotoxicity testing.Journal of tissue engineering and regenerative medicine · 2022Article
- Model systems and organisms for addressing inter- and intra-species variability in risk assessment.Regulatory toxicology and pharmacology : RTP · 2022Review
- Identifying Acute Cardiac Hazard in Early Drug Discovery Using a Calcium Transient High-Throughput Assay in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes.Frontiers in physiology · 2022Article
- Potential Human Health Hazard of Post-Hurricane Harvey Sediments in Galveston Bay and Houston Ship Channel: A Case Study of UsingInternational journal of environmental research and public health · 2021Article
- Cardiotoxicity Hazard and Risk Characterization of ToxCast Chemicals Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes from Multiple Donors.Chemical research in toxicology · 2021Article
- Key Characteristics of Cardiovascular Toxicants.Environmental health perspectives · 2021Article
- Relationships between constituents of energy drinks and beating parameters in human induced pluripotent stem cell (iPSC)-Derived cardiomyocytes.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2021Article
- Risk Characterization and Probabilistic Concentration-Response Modeling of Complex Environmental Mixtures Using New Approach Methodologies (NAMs) Data from OrganotypicEnvironmental health perspectives · 2021Article
- A Bayesian Method for Population-wide Cardiotoxicity Hazard and Risk Characterization Using an In Vitro Human Model.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
Corrections and comments
- Commented on by
- Erratum issuedCORRIGENDUM: Thorough QT/QTc in a Dish: An In Vitro Human Model That Accurately Predicts Clinical Concentration-QTc Relationships.2019 · Dalaijamts, Chimedullam [corrected to Dalaijamts, Chimeddulam]
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
"Thorough QT/corrected QT (QTc)" (TQT) studies are cornerstones of clinical cardiovascular safety assessment. However, TQT studies are resource intensive, and preclinical models predictive of the threshold of regulatory concern are lacking. We hypothesized that an in vitro model using induced pluripotent stem cell (iPSC)-derived cardiomyocytes from a diverse sample of human subjects can serve as a "TQT study in a dish." For 10 positive and 3 negative control drugs, in vitro concentration-QTc, computed using a population Bayesian model, accurately predicted known in vivo concentration-QTc. Moreover, predictions of the percent confidence that the regulatory threshold of 10 ms QTc prolongation would be breached were also consistent with in vivo evidence. This "TQT study in a dish," consisting of a population-based iPSC-derived cardiomyocyte model and Bayesian concentration-QTc modeling, has several advantages over existing in vitro platforms, including higher throughput, lower cost, and the ability to accurately predict the in vivo concentration range below the threshold of regulatory concern.
Indexed as
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What OpenQuestion holds
Registered trials
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.