ReviewJournal of pharmacokinetics and pharmacodynamics2018
Scientific white paper on concentration-QTc modeling.
Review in Journal of pharmacokinetics and pharmacodynamics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 2 registered trials, which are not on this map. Cited by 140 papers, 3 of them syntheses 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.
A Phase 1, Two-Part Study in Healthy Volunteers to Evaluate The Effect of Psilocybin on Cardiac Repolarization and The Effect of Food on Psilocybin Pharmacokinetics
Clinical ECG Study to Evaluate Electrophysiological Effects of Potential QT Prolonging Drugs With Novel ECG Biomarkers With Exposure-Response Analysis
Who cites it
140 citing papers in PubMed, 3 syntheses or guidelines pooled it, 250 citations in OpenAlex.
- QT Prolongation Risk of Antibody-Drug Conjugates.Drug safety · 2026Pooled it
- Effects of Nacubactam and Its Metabolites on QTc Interval: A Pooled Analysis of Two Randomized Phase 1 Studies.Clinical and translational science · 2026Pooled it
- Evaluation of the potential for QTc prolongation with avelumab.Cancer chemotherapy and pharmacology · 2019Pooled it
- Concentration-QTc Analysis Supporting Thorough QT Study Waiver for Forvisirvat: Electrocardiogram Assay Sensitivity Demonstrated via Meal Effect.Journal of clinical pharmacology · 2026Trial
- Safety, Tolerability, Pharmacokinetics, Food Effect of Ribitol, and Its Effect on QTcF in Healthy Adults: First-in-Human, Randomized, Double-Blind (Sponsor Unblinded), Placebo-Controlled Studies.Clinical pharmacology in drug development · 2026Trial
- Thorough QT/QTc Clinical Study to Evaluate the Effect of Remdesivir on Cardiac Repolarization in Healthy Participants.Clinical and translational science · 2026Trial
- 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
- Cardiodynamic evaluation of sorfequiline (TBAJ-876): results from a first-in-human study.Antimicrobial agents and chemotherapy · 2026Trial
- Thorough QT Study on the Effect of Therapeutic and Supratherapeutic Dosing of Givinostat in Healthy Volunteers.Clinical pharmacology in drug development · 2026Trial
- Evaluation of clinical cardiac safety of zilurgisertib, an activin receptor-like kinase-2 (ALK2) inhibitor, in healthy participants.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
- Pharmacokinetics, Tolerability, and Biomarker Profile of the Neurokinin 3 Receptor Antagonist Fezolinetant in Healthy Japanese Individuals: A 2-Part, Randomized, Phase 1 Study.Clinical pharmacology in drug development · 2025Trial
- Assessment of the Effects of Fruquintinib on Cardiac Safety in Patients with Metastatic Colorectal Cancer.Journal of clinical pharmacology · 2025Trial
- No Evidence of QTc Interval Prolongation With Baxdrostat Treatment: Concentration-QTc Modeling Assessment.Pharmacology research & perspectives · 2025Trial
- 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
- Establishing the Exposure-QT Relationship During Bedaquiline Treatment Using a Time-Varying Tuberculosis-Specific Correction Factor (QTcTBT).CPT: pharmacometrics & systems pharmacology · 2025Trial
- Concentration-Response Analysis of the Combination of Pyronaridine and Piperaquine on Corrected QT Interval From a Randomized, Double-Blind, Placebo-Controlled Study in Healthy Adults of African Sub-Saharan Origin.Clinical and translational science · 2025Trial
- Quantifying Risk of Delayed QT Prolongation of Ipatasertib in Preclinical and Clinical Studies in Cancer Patients.Clinical and translational science · 2025Trial
- Clinical Evaluation of the Effect of Aficamten on QT/QTc Interval in Healthy Participants.Clinical and translational science · 2025Trial
- Single- and multiple-dose pharmacokinetics and safety of the SARS-CoV-2 3CL protease inhibitor RAY1216: a phase 1 study in healthy participants.Antimicrobial agents and chemotherapy · 2025Trial
80 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The International Council for Harmonisation revised the E14 guideline through the questions and answers process to allow concentration-QTc (C-QTc) modeling to be used as the primary analysis for assessing the QTc interval prolongation risk of new drugs. A well-designed and conducted QTc assessment based on C-QTc modeling in early phase 1 studies can be an alternative approach to a thorough QT study for some drugs to reliably exclude clinically relevant QTc effects. This white paper provides recommendations on how to plan and conduct a definitive QTc assessment of a drug using C-QTc modeling in early phase clinical pharmacology and thorough QT studies. Topics included are: important study design features in a phase 1 study; modeling objectives and approach; exploratory plots; the pre-specified linear mixed effects model; general principles for model development and evaluation; and expectations for modeling analysis plans and reports. The recommendations are based on current best modeling practices, scientific literature and personal experiences of the authors. These recommendations are expected to evolve as their implementation during drug development provides additional data and with advances in analytical methodology.
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.