ReviewBritish journal of clinical pharmacology2013
Early QT assessment--how can our confidence in the data be improved?
Review in British journal of clinical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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
23 citing papers in PubMed.
- Population pharmacokinetics and electrocardiographic effects of dihydroartemisinin-piperaquine in healthy volunteers.British journal of clinical pharmacology · 2017Trial
- Comparison of Digital 12-Lead ECG and Digital 12-Lead Holter ECG Recordings in Healthy Male Subjects: Results from a Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2016Trial
- Can an early phase clinical pharmacology study replace a thorough QT study? Experience with a novel H3-receptor antagonist/inverse agonist.European journal of clinical pharmacology · 2016Trial
- Establishing assay sensitivity in QT studies: experience with the use of moxifloxacin in an early phase clinical pharmacology study and comparison with its effect in a thorough QT study.European journal of clinical pharmacology · 2015Trial
- 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
- Risks encountered when not adjusting for diurnal variation and food effect in QTcF analysis based on phase I data.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- Pridopidine Does Not Significantly Prolong the QTc Interval at the Clinically Relevant Therapeutic Dose.Neurology and therapy · 2023Article
- 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
- 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
- Nonclinical cardiovascular safety of pitolisant: comparing International Conference on Harmonization S7B and Comprehensive in vitro Pro-arrhythmia Assay initiative studies.British journal of pharmacology · 2017Article
- Estimation of QT interval prolongation through model-averaging.Journal of pharmacokinetics and pharmacodynamics · 2017Article
- Comparing QT interval variability of semiautomated and high-precision ECG methodologies in seven thorough QT studies-implications for the power of studies intended for definitive evaluation of a drug's QT effect.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2017Article
- Implications of the IQ-CSRC Prospective Study: Time to Revise ICH E14.Drug safety · 2015Article
- Detection of QTc effects in small studies--implications for replacing the thorough QT study.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2015Article
- The Power of Phase I Studies to Detect Clinical Relevant QTc Prolongation: A Resampling Simulation Study.BioMed research international · 2015Article
- Evaluating the Use of Linear Mixed-Effect Models for Inference of the Concentration-QTc Slope Estimate as a Surrogate for a Biological QTc Model.CPT: pharmacometrics & systems pharmacology · 2015Article
- The role of concentration-effect relationships in the assessment of QTc interval prolongation.British journal of clinical pharmacology · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exposure-response (ER) analysis has emerged as an important tool to interpret QT data from thorough QT (TQT) studies and allows the prediction of effects in the targeted patient population. Recently, ER analysis has also been applied to data from early clinical pharmacology studies, such as single and multiple ascending dose studies, in which high plasma concentrations are often achieved. In line with this, there is an on-going discussion between sponsors, academicians and regulators on whether 'early QT assessment' can provide sufficiently high confidence in assessment of QT prolongation to replace the TQT study. In this article, we discuss how QT assessment can be applied to early clinical studies ('early QT assessment') and what we believe is needed to achieve the same high confidence in the data as we currently obtain from data from the TQT study. The power to exclude a QTc effect exceeding 10 ms in small sample sizes using ER analysis will be discussed and compared with time-matched analysis, as described in the ICH E14 guidance. Two examples of early QT assessment are shared; one negative and one positive, and the challenge in terms of demonstrating assay sensitivity in the absence of a pharmacological positive control will be discussed. Finally, we describe a recent research proposal, which may generate data to support the replacement of the TQT study with data from QT assessment in early phase 1 studies.
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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.