ReviewBritish journal of pharmacology2010
Update on the evaluation of a new drug for effects on cardiac repolarization in humans: issues in early drug development.
Review in British journal of pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 citations in OpenAlex.
- Losmapimod concentration-QT relationship in healthy volunteers: meta-analysis of data from six clinical trials.European journal of clinical pharmacology · 2013Pooled it
- A Randomized, Double-Blinded, Placebo-Controlled QTc Study to Evaluate BIA 28-6156 Effect on Cardiac Repolarization in Healthy Volunteers.Clinical pharmacology in drug development · 2026Trial
- A Thorough QT Study to Assess the Effects of Milvexian on Cardiac Repolarization in Healthy Participants.Clinical pharmacology in drug development · 2026Trial
- Thorough QT Study To Evaluate the Effect of Zoliflodacin, a Novel Therapeutic for Gonorrhea, on Cardiac Repolarization in Healthy Adults.Antimicrobial agents and chemotherapy · 2021Trial
- Comparing the consistency of electrocardiogram interval measurements by resting ECG versus 12-lead Holter.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2021Trial
- Evaluation of the Effect of Contezolid (MRX-I) on the Corrected QT Interval in a Randomized, Double-Blind, Placebo- and Positive-Controlled Crossover Study in Healthy Chinese Volunteers.Antimicrobial agents and chemotherapy · 2020Trial
- Effect of Therapeutic and Supratherapeutic Doses of Vonoprazan on the QT/QTc Interval in a Phase I Randomized Study in Healthy Subjects.Clinical and translational science · 2017Trial
- No Apparent Cardiac Conduction Effects of Acute Treatment with Risperidone in Children with Autism Spectrum Disorder.Journal of child and adolescent psychopharmacology · 2016Trial
- Detecting moxifloxacin-induced QTc prolongation in thorough QT and early clinical phase studies using a highly automated ECG analysis approach.British journal of pharmacology · 2016Trial
- A thorough QT study to assess the effects of tbo-filgrastim on cardiac repolarization in healthy subjects.Drug design, development and therapy · 2015Trial
- Model-based evaluation of drug-induced QTc prolongation for compounds in early development.British journal of clinical pharmacology · 2015Trial
- A repeat-dose thorough QT study of inhaled fluticasone furoate/vilanterol combination in healthy subjects.British journal of clinical pharmacology · 2014Trial
- Thorough QT study of the effect of oral moxifloxacin on QTc interval in the fed and fasted state in healthy Japanese and Caucasian subjects.British journal of clinical pharmacology · 2014Trial
- Effects of atomoxetine on the QT interval in healthy CYP2D6 poor metabolizers.British journal of clinical pharmacology · 2013Trial
- Case report: Phosphoinositide 3-kinase inhibitor with fulvestrant in a patient with ER+/HER2- metastatic breast carcinoma induced fatal arrhythmias: a preventable event?Frontiers in oncology · 2024Article
- Characterizing complex and competing drug-drug interactions between the antiviral regimen of glecaprevir and pibrentasvir with rifampin or carbamazepine.Clinical and translational science · 2023Article
- QTc Interval Reference Values and Their (Non)-Maturational Factors in Neonates and Infants: A Systematic Review.Children (Basel, Switzerland) · 2022Review
- Exposure-response analysis of adverse events associated with molibresib and its active metabolites in patients with solid tumors.CPT: pharmacometrics & systems pharmacology · 2022Article
- Management of Adverse Events Associated with Cabozantinib Treatment in Patients with Advanced Hepatocellular Carcinoma.Targeted oncology · 2020Article
- Combining an in silico proarrhythmic risk assay with a tPKPD model to predict QTc interval prolongation in the anesthetized guinea pig assay.Toxicology and applied pharmacology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Following reports of death from cardiac arrhythmias with drugs like terfenadine and cisapride, the International Conference for Harmonization formulated a guidance (E14) document. This specifies that all new drugs must undergo a 'thorough QT/QTc' (TQT) study to detect drug-induced QT prolongation, a surrogate marker of ventricular tachycardia, especially torsades de pointes (TdPs). With better understanding of data from several completed TQT studies, regulatory requirements have undergone some changes since the E14 guidance was implemented in October 2005. This article reviews the implications of the E14 guidance and the changes in its interpretation including choice of baseline QT, demonstration of assay sensitivity, statistical analysis of the effect of new drug and positive control, and PK-PD modelling. Some issues like use of automated QT measurements remain unresolved. Pharmaceutical companies too are modifying Phase 1 studies to detect QTc liability early in order to save time and resources. After the E14 guidance, development of several drugs that prolong QTc by >5 ms is being abandoned by sponsors. However, all drugs that prolong the QT interval do not increase risk of TdP. Researchers in regulatory agencies, academia and industry are working to find better biomarkers of drug-induced TdP which could prevent many useful drugs from being prematurely abandoned. Drug-induced TdP is a rare occurrence. With fewer drugs that prolong QT interval reaching the licensing stage, knowing which of these drugs are torsadogenic is proving to be elusive. Thus, paradoxically, the effectiveness of the E14 guidance itself has made prospective validation of new biomarkers difficult.
Indexed as
Identifiers
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.