Article
Differences between QT and RR intervals in digital and digitized paper electrocardiograms: contribution of the printer, scanner, and digitization process.
Research Section, Quintiles ECG Services, Mumbai, India.
Journal of electrocardiology (impact factor:
1.08).
06/2008;
41(5):370-5.
DOI:10.1016/j.jelectrocard.2008.02.026
Source: PubMed
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Citations (0)
- Cited In (1)
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Article: Update on the evaluation of a new drug for effects on cardiac repolarization in humans: issues in early drug development.
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ABSTRACT: Following reports of death from cardiac arrhythmias with drugs like terfenadine and cisapride, the International Conference for Harmonization formulated a guidance (E14) document. This specifies that all new drugs must undergo a 'thorough QT/QTc' (TQT) study to detect drug-induced QT prolongation, a surrogate marker of ventricular tachycardia, especially torsades de pointes (TdPs). With better understanding of data from several completed TQT studies, regulatory requirements have undergone some changes since the E14 guidance was implemented in October 2005. This article reviews the implications of the E14 guidance and the changes in its interpretation including choice of baseline QT, demonstration of assay sensitivity, statistical analysis of the effect of new drug and positive control, and PK-PD modelling. Some issues like use of automated QT measurements remain unresolved. Pharmaceutical companies too are modifying Phase 1 studies to detect QTc liability early in order to save time and resources. After the E14 guidance, development of several drugs that prolong QTc by >5 ms is being abandoned by sponsors. However, all drugs that prolong the QT interval do not increase risk of TdP. Researchers in regulatory agencies, academia and industry are working to find better biomarkers of drug-induced TdP which could prevent many useful drugs from being prematurely abandoned. Drug-induced TdP is a rare occurrence. With fewer drugs that prolong QT interval reaching the licensing stage, knowing which of these drugs are torsadogenic is proving to be elusive. Thus, paradoxically, the effectiveness of the E14 guidance itself has made prospective validation of new biomarkers difficult.British Journal of Pharmacology 09/2009; 159(1):34-48. · 4.41 Impact Factor
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Keywords
2 different manufacturers
2 prints
2 readings
2 scanned files
21 milliseconds
50 digital ECGs
50 digitized ECGs
50 prints
50 scanned files
50 volunteers
Digital ECGs
digital format
digitization process account
digitization software
digitized ECGs
intrareader variability
machine 1
machine 2. Contributions
reader variability
RR interval measurement