Skip to main content
SpringerLink
Log in

Validation of QT Interval Correction Methods When a Drug Changes Heart Rate

  • Drug Safety
  • Published:
Therapeutic Innovation & Regulatory Science Aims and scope Submit manuscript

Abstract

The QT interval is correlated with heart rate; therefore, the QT interval is usually corrected by heart rate when drug-induced QT effect is studied. Currently, there are many correction methods that use either fixed or data-driven approaches. The effectiveness of correction methods depends on many factors and varies from study to study. Statistical validation and comparisons need to be performed to determine the most appropriate correction method for each study. We examined different validation methods and explored a new approach to use when the testing drug changes heart rate.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. International Conference on Harmonisation. Guidance on E14 clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs: availability. Notice. Fed Regist. 2005;70:61134–61135.

    Google Scholar 

  2. Badilini F, Maison-Blanche P, Childers R, et al. QT interval analysis on ambulatory electrocardiogram recordings: a selective beat averaging approach. Med Biol Eng Comput. 1999;37:71–79.

    Article  CAS  Google Scholar 

  3. Fossa AA, Wisialowski T, Magnano A, et al. Dynamic beat-to-beat modeling of the QT-RR interval relationship: analysis of QT prolongation during alterations of autonomic state versus human ether a-go-go-related gene inhibition. J Pharmacol Exp Ther. 2005;312:1–11.

    Article  CAS  Google Scholar 

  4. Fossa AA, Zhou M. Assessing QT prolongation and electrocardiography restitution using a beat-to-beat method. Cardiol J. 2010;17(3):230–243.

    PubMed  Google Scholar 

  5. Hosmane B, Locke C, Morris D. QT interval: correction for heart rate. J Appl Res. 2006;6:288–299.

    Google Scholar 

  6. Malik M. Problems of heart rate correction in the assessment of drug-induced QT interval prolongation. J Cardiovasc Electrophysiol. 2001;12:411–420.

    Article  CAS  Google Scholar 

  7. Malik M, Färbom P, Batchvarov V, Hnatkova K, Camm AJ. Relation between QT and RR intervals is highly individual among healthy subjects: implications for heart rate correction of the QT interval. Heart. 2002;87:220–228.

    Article  CAS  Google Scholar 

  8. Malik M, Hnatkova K, Batchvarov V. Differences between study-specific and subject-specific heart rate corrections of the QT interval in investigations of drug induced QTc prolongation. Pacing Clin Electrophysiol. 2004;27 (6/1):791–800.

    Article  Google Scholar 

  9. Batchvarov V, Malik M, Färbom P. Individual patterns of QT/RR relationship. Cardiac Electrophysiol Rev. 2002;6:282–288.

    Article  Google Scholar 

  10. Ring A. Statistical models for heart rate correction of the QT interval. Stat Med. 2009;29:786–796.

    Article  Google Scholar 

  11. Dmitrienko A, Smith B. Repeated-measures models in the analysis of QT interval. Pharm Stat. 2003;2(3):175–190.

    Article  Google Scholar 

  12. Garnett CE, Beasley N, Atul Bhattaram V, et al. Concentration–QT relationships play a key role in the evaluation of proarrhythmic risk during regulatory review. J Clin Pharmacol. 2008;48(1):13–18.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Biometrics VI, Office of Biostatistics, Center of Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, 20903, USA

    Qianyu Dang PhD & Joanne Zhang PhD

Authors
  1. Qianyu Dang PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joanne Zhang PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qianyu Dang PhD.

Additional information

This article reflects the views of the authors and should not be construed to represent FDA’s views or policies.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dang, Q., Zhang, J. Validation of QT Interval Correction Methods When a Drug Changes Heart Rate. Ther Innov Regul Sci 47, 256–260 (2013). https://doi.org/10.1177/2168479012467018

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/2168479012467018

Keywords

Search

Navigation