ReviewAnnals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc2014
The IQ-CSRC prospective clinical Phase 1 study: "Can early QT assessment using exposure response analysis replace the thorough QT study?".
Review in Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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
40 citing papers in PubMed, 99 citations in OpenAlex.
- Assessment of QT Interval Prolongation Using Concentration-QT Modeling for Iptacopan, an Oral Complement Factor B Inhibitor, in Healthy Individuals.Clinical and translational science · 2025Trial
- Evaluation of the Effect of Loperamide on the Cardiac Repolarization Interval Using Exposure-Response Analysis.Clinical and translational science · 2025Trial
- No QT interval prolongation effect of sepiapterin: a concentration-QTc analysis of pooled data from phase 1 and phase 3 studies in healthy volunteers and patients with phenylketonuria.Journal of pharmacokinetics and pharmacodynamics · 2025Trial
- Abemaciclib does not increase the corrected QT interval in healthy participants.Clinical and translational science · 2023Trial
- Evaluation of the potential effect of dacomitinib, an EGFR tyrosine kinase inhibitor, on ECG parameters in patients with advanced non-small cell lung cancer.Investigational new drugs · 2020Trial
- Evaluation of the Cardiac Safety of Long-Acting Endectocide Moxidectin in a Randomized Concentration-QT Study.Clinical and translational science · 2018Trial
- Assessing QT/QTc interval prolongation with concentration-QT modeling for Phase I studies: impact of computational platforms, model structures and confidence interval calculation methods.Journal of pharmacokinetics and pharmacodynamics · 2018Trial
- Palbociclib has no clinically relevant effect on the QTc interval in patients with advanced breast cancer.Anti-cancer drugs · 2018Trial
- Lack of QT Prolongation for 2'-O-Methoxyethyl-Modified Antisense Oligonucleotides Based on Retrospective Exposure/Response Analysis of Ten Phase 1 Dose-Escalation Placebo-Controlled Studies in Healthy Subjects.Nucleic acid therapeutics · 2017Trial
- Evaluation of the QT effect of a combination of piperaquine and a novel anti-malarial drug candidate OZ439, for the treatment of uncomplicated malaria.British journal of clinical pharmacology · 2015Trial
- Safety, pharmacokinetics, pharmacogenomics and QT concentration-effect modelling of the SirT1 inhibitor selisistat in healthy volunteers.British journal of clinical pharmacology · 2015Trial
- Trial
- Platform Assessment of Concentration-QTc Relationship Across GalNAc-siRNA Molecules.Clinical pharmacokinetics · 2026Article
- ECG Evaluation as Part of the Clinical Pharmacology Strategy in the Development of New Drugs: A Review of Current Practices and Opportunities Based on Five Case Studies.Journal of clinical pharmacology · 2022Review
- Exposure-response analysis of adverse events associated with molibresib and its active metabolites in patients with solid tumors.CPT: pharmacometrics & systems pharmacology · 2022Article
- The New S7B/E14 Question and Answer Draft Guidance for Industry: Contents and Commentary.Journal of clinical pharmacology · 2021Review
- QTc interval analysis-an ever-evolving endeavor.Journal of pharmacokinetics and pharmacodynamics · 2021Article
- Application of Trial Simulation in the Design of a Prospective Study for Concentration-QTc Analysis in Support of a Thorough QT Study Waiver.The AAPS journal · 2020Article
- First-in-Human, Healthy Volunteers Integrated Protocol of ETC-206, an Oral Mnk 1/2 Kinase Inhibitor Oncology Drug.Clinical and translational science · 2020Article
- Cardiac risk assessment based on early Phase I data and PK-QTc analysis is concordant with the outcome of thorough QTc trials: an assessment based on eleven drug candidates.Journal of pharmacokinetics and pharmacodynamics · 2019Article
Corrections and comments
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Authors and funding
14 authors at 11 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A collaboration between the Consortium for Innovation and Quality in Pharmaceutical Development and the Cardiac Safety Research Consortium has been formed to design a clinical study in healthy subjects demonstrating that the thorough QT (TQT) study can be replaced by robust ECG monitoring and exposure-response (ER) analysis of data generated from First-in-Man single ascending dose (SAD) studies. Six marketed drugs with well-characterized QTc effects were identified in discussions with FDA; five have caused QT prolongation above the threshold of regulatory concern. Twenty healthy subjects will be enrolled in a randomized, placebo-controlled study designed with the intent to have similar power to exclude small QTc effects as a SAD study. Two doses (low and high) of each drug will be given on separate, consecutive days to 9 subjects. Six subjects will receive placebo. Data will be analyzed using linear mixed-effects ER models. Criteria for QT-positive drugs will be the demonstration of an upper bound (UB) of the 2-sided 90% confidence interval (CI) of the projected QTc effect at the peak plasma level of the lower dose above the threshold of regulatory concern (currently 10 ms) and a positive slope of ER relationship. The criterion for QT-negative drug will be an UB of the CI of the projected QTc effect of the higher dose <10 ms. It is expected that a successful outcome in this study will provide evidence supporting replacement of the TQT study with ECG assessments in standard early clinical development studies for a new chemical entity.
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.