ArticleBioMed research international2015
The Power of Phase I Studies to Detect Clinical Relevant QTc Prolongation: A Resampling Simulation Study.
Article in BioMed research international, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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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.
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Who cites it
11 citing papers in PubMed.
- Population pharmacokinetic/pharmacodynamic modeling of nifekalant injection with varies dosing plan in Chinese volunteers: a randomized, blind, placebo-controlled study.Journal of pharmacokinetics and pharmacodynamics · 2024Trial
- A randomized, double-blind, placebo- and positive-controlled crossover study of the effects of durlobactam on cardiac repolarization in healthy subjects.Clinical and translational science · 2021Trial
- Trial
- Estimation of the Power of the Food Effect on QTc to Show Assay Sensitivity.Journal of clinical pharmacology · 2018Trial
- Sample size determination for cardiodynamic ECG assessment using the Concentration-QTc analysis method.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- A comprehensive regulatory and industry review of modeling and simulation practices in oncology clinical drug development.Journal of pharmacokinetics and pharmacodynamics · 2023Review
- 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
- Scientific white paper on concentration-QTc modeling.Journal of pharmacokinetics and pharmacodynamics · 2018Review
- Effect of ulixertinib, a novel ERK1/2 inhibitor, on the QT/QTc interval in patients with advanced solid tumor malignancies.Cancer chemotherapy and pharmacology · 2018Article
- Evaluating cardiac risk: exposure response analysis in early clinical drug development.Drug, healthcare and patient safety · 2018Review
- 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
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Concentration-effect (CE) models applied to early clinical QT data from healthy subjects are described in the latest E14 Q&A document as promising analysis to characterise QTc prolongation. The challenges faced if one attempts to replace a TQT study by thorough ECG assessments in Phase I based on CE models are the assurance to obtain sufficient power and the establishment of a substitute for the positive control to show assay sensitivity providing protection against false negatives. To demonstrate that CE models in small studies can reliably predict the absence of an effect on QTc, we investigated the role of some key design features in the power of the analysis. Specifically, the form of the CE model, inclusion of subjects on placebo, and sparse sampling on the performance and power of this analysis were investigated. In this study, the simulations conducted by subsampling subjects from 3 different TQT studies showed that CE model with a treatment effect can be used to exclude small QTc effects. The number of placebo subjects was also shown to increase the power to detect an inactive drug preventing false positives while an effect can be underestimated if time points around t max are missed.
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