ArticleDrug safety2019
Implications of Individual QT/RR Profiles-Part 1: Inaccuracies and Problems of Population-Specific QT/Heart Rate Corrections.
Article in Drug safety, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- A Thorough QT Study to Assess the Effects of Milvexian on Cardiac Repolarization in Healthy Participants.Clinical pharmacology in drug development · 2026Trial
- Impact of Daridorexant, a Dual Orexin Receptor Antagonist, on Cardiac Repolarization Following Bedtime Dosing: Results from a Thorough QT Study Using Concentration-QT Analysis.Clinical drug investigation · 2021Trial
- Effect of Clofazimine Concentration on QT Prolongation in Patients Treated for Tuberculosis.Antimicrobial agents and chemotherapy · 2021Trial
- Randomized, Double-Blind, Placebo- and Positive-Controlled Crossover Study of the Effects of Omadacycline on QT/QTc Intervals in Healthy Subjects.Antimicrobial agents and chemotherapy · 2019Trial
- Intra-subject covariates of QT variability indices: influence of ECG noise.Frontiers in physiology · 2026Article
- Concentration QTc analysis of giredestrant: Overcoming QT/heart rate confounding in the presence of drug-induced heart rate changes.Clinical and translational science · 2023Article
- Pharmacometric and Electrocardiographic Evaluation of Chloroquine and Azithromycin in Healthy Volunteers.Clinical pharmacology and therapeutics · 2022Article
- Influence of heart rate correction formulas on QTc interval stability.Scientific reports · 2021Article
- Problems with Bazett QTc correction in paediatric screening of prolonged QTc interval.BMC pediatrics · 2020Article
- Implications of Individual QT/RR Profiles-Part 2: Zero QTc/RR Correlations Do Not Prove QTc Correction Accuracy in Studies of QTc Changes.Drug safety · 2019Article
- Correcting QT for Heart Rate When Both are Affected by a Drug.Drug safety · 2019Article
- Individually Rate Corrected QTc Intervals in Children and Adolescents.Frontiers in physiology · 2019Article
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
6 authors.
Funding
Abstract
introductionUniversal QT correction formulas are potentially problematic in corrected QT (QTc) interval comparisons at different heart rates. Instead of individual-specific corrections, population-specific corrections are occasionally used based on QT/RR data pooled from all study subjects.
objectiveTo investigate the performance of individual-specific and population-specific corrections, a statistical modeling study was performed using QT/RR data of 523 healthy subjects.
methodsIn each subject, full drug-free QT/RR profiles were available, characterized using non-linear regression models. In each subject, 50 baseline QT/RR readings represented baseline data of standard QT studies. Using these data, linear and log-linear heart rate corrections were optimized for each subject and for different groups of ten and 50 subjects. These corrections were applied in random combinations of heart rate changes between - 10 and + 25 beats per minute (bpm) and known QTc interval changes between - 25 and + 25 ms.
resultsBoth the subject-specific and population-specific corrections based on the 50 baseline QT/RR readings tended to underestimate/overestimate the QTc interval changes when heart rate was increasing/decreasing, respectively. The result spread was much wider with population-specific corrections, making the estimates of QTc interval changes practically unpredictable.
conclusionSubject-specific heart rate corrections based on limited baseline drug-free data may lead to inconsistent results and, in the presence of underlying heart rate changes, may potentially underestimate or overestimate QTc interval changes. The population-specific corrections lead to results that are much more influenced by the combination of individual QT/RR patterns than by the actual QTc interval changes. Subject-specific heart rate corrections based on full profiles derived from drug-free baseline recordings with wide QT/RR distribution should be used when studying drugs expected to cause heart rate changes.
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