Translational models and tools to reduce clinical trials and improve regulatory decision making for QTc and proarrhythmia risk (ICH E14/S7B updates)
DG Strauss, WW Wu, Z Li, J Koerner… - Clinical Pharmacology …, 2021 - Wiley Online Library
After multiple drugs were removed from the market secondary to drug‐induced torsade de
pointes (TdP) risk, the International Council for Harmonisation (ICH) released guidelines in …
pointes (TdP) risk, the International Council for Harmonisation (ICH) released guidelines in …
The 'Digital Twin'to enable the vision of precision cardiology
J Corral-Acero, F Margara, M Marciniak… - European heart …, 2020 - academic.oup.com
Providing therapies tailored to each patient is the vision of precision medicine, enabled by
the increasing ability to capture extensive data about individual patients. In this position …
the increasing ability to capture extensive data about individual patients. In this position …
Creation and application of virtual patient cohorts of heart models
SA Niederer, Y Aboelkassem… - … of the Royal …, 2020 - royalsocietypublishing.org
Patient-specific cardiac models are now being used to guide therapies. The increased use
of patient-specific cardiac simulations in clinical care will give rise to the development of …
of patient-specific cardiac simulations in clinical care will give rise to the development of …
Assessment of an In Silico Mechanistic Model for Proarrhythmia Risk Prediction Under the CiPA Initiative
The International Council on Harmonization (ICH) S7B and E14 regulatory guidelines are
sensitive but not specific for predicting which drugs are pro‐arrhythmic. In response, the …
sensitive but not specific for predicting which drugs are pro‐arrhythmic. In response, the …
[HTML][HTML] Machine learning in drug development: Characterizing the effect of 30 drugs on the QT interval using Gaussian process regression, sensitivity analysis, and …
Prolonged QT intervals are a major risk factor for ventricular arrhythmias and a leading
cause of sudden cardiac death. Various drugs are known to trigger QT interval prolongation …
cause of sudden cardiac death. Various drugs are known to trigger QT interval prolongation …
Comprehensive in vitro proarrhythmia assay (CiPA) update from a cardiac safety research consortium/health and environmental sciences institute/FDA meeting
DG Strauss, G Gintant, Z Li, W Wu… - Therapeutic …, 2019 - journals.sagepub.com
A Cardiac Safety Research Consortium/Health and Environmental Sciences Institute/FDA-
sponsored Think Tank Meeting was convened in Washington, DC, on May 21, 2018, to bring …
sponsored Think Tank Meeting was convened in Washington, DC, on May 21, 2018, to bring …
Prediction of arrhythmia susceptibility through mathematical modeling and machine learning
At present, the QT interval on the electrocardiographic (ECG) waveform is the most common
metric for assessing an individual's susceptibility to ventricular arrhythmias, with a long QT …
metric for assessing an individual's susceptibility to ventricular arrhythmias, with a long QT …
Comprehensive uncertainty quantification and sensitivity analysis for cardiac action potential models
Recent efforts to ensure the reliability of computational model-based predictions in
healthcare, such as the ASME V&V40 Standard, emphasize the importance of uncertainty …
healthcare, such as the ASME V&V40 Standard, emphasize the importance of uncertainty …
Drug‐induced shortening of the electromechanical window is an effective biomarker for in silico prediction of clinical risk of arrhythmias
Background and Purpose Early identification of drug‐induced cardiac adverse events is key
in drug development. Human‐based computer models are emerging as an effective …
in drug development. Human‐based computer models are emerging as an effective …
[HTML][HTML] Digital twinning of the human ventricular activation sequence to Clinical 12-lead ECGs and magnetic resonance imaging using realistic Purkinje networks for …
Cardiac in silico clinical trials can virtually assess the safety and efficacy of therapies using
human-based modelling and simulation. These technologies can provide mechanistic …
human-based modelling and simulation. These technologies can provide mechanistic …