Abstract
The prospective exclusion of unacceptable cardiac and cardiovascular risk has become a critical component of drug safety evaluation in new drug development. At the end of Chapter 4 we discussed the cardiac safety evaluations conducted in a nonclinical research program that are specifically focused on assessing if the drug molecule may impact the hERG current flowing through hERG ion channels and hence lead to QT interval prolongation (or shortening). In this chapter discussions focus on analogous evaluations in humans if a sponsor decides to move the drug molecule into clinical trials. At this point, the term investigational drug can be adopted.
A useful approach to prospectively excluding unacceptable cardiac and cardiovascular risks can be conceptualized in a three-component model comprising clinical, regulatory, and statistical science.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Further Readings
Beasley CM Jr, Dmitrienko A, Mitchell MI, 2008, Design and analysis considerations for thorough QT studies employing conventional (10s, 12-lead) ECG recordings, Expert Review in Clinical Pharmacology, 1:815–839.
Caveney E, Turner JR, 2010, Regulatory landscapes for future antidiabetic drug development (Part I): FDA guidance on assessment of cardiovascular risk. Journal for Clinical Studies, January issue, 34–36.
Turner JR, Durham, 2009, Integrated Cardiac Safety: Assessment Methodologies for Non-cardiac Drugs in Discovery, Development, and Postmarketing Surveillance. Hoboken, NJ: Wiley.
Vaibhav S, Karnard DR, Panicker GP, Kothari S, 2009, Update on the evaluation of a new drug for effects on cardiac repolarization in humans: Issues in early drug development. British Journal of Pharmacology, 159:34–38.
Turner JR, Durham TA, 2009, Integrated Cardiac Safety: Assessment Methodologies for Noncardiac Drugs in Discovery, Development, and Postmarketing Surveillance. Hoboken, NJ: Wiley.
Nissen SE, Wolski K, 2007, Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. New England Journal of Medicine, 356: 2,457–2,471.
Rock EP, Finkle J, Fingert HJ, et al., 2009, Assessing proarrhythmic potential of drugs when optimal studies are infeasible. American Heart Journal, 157:827–836.
Borer JS, Pouleur H, Abadie E, et al., 2007, Cardiovascular safety of drugs not intended for cardiovascular use: Need for a new conceptual basis for assessment and approval. European Heart Journal, 28:1904–1909.
Whitehead A, 2002, Meta-analysis of Controlled Clinical Trials. Hoboken, NJ: Wiley.
Brass EP, Lewis RJ, Lipicky R, Murphy J, Hiatt WR, 2006, Risk assessment in drug development for symptomatic indications: A framework for the prospective exclusion of unacceptable cardiovascular risk. Clinical Pharmacology and Therapeutics, 75:165–172.
De Ponti F, 2008, Pharmacological and regulatory aspects of QT prolongation. In Vaz RJ, Klabunde T (Eds), Antitargets: Prediction and Prevention of Drug Side Effects. Weinheim, Germany: Wiley-VCH.
Morganroth J, Brozovich FV, McDonald JT, Jacobs RA, 1991, Variability of the QT measurement in health men: With implications for selection of an abnormal QT value to predict drug toxicity and proarrhythmia. American Journal of Cardiology, 67:774–776.
Diamond GA, Bax L, Kaul S, 2007, Perspective: Uncertain effects of rosiglitazone on the risk for myocardial infarction and cardiovascular death. Annals of Internal Medicine, 147:578–581.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
Copyright information
© 2011 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Turner, J.R. (2011). Cardiac and Cardiovascular Safety Assessments. In: New Drug Development. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6418-2_14
Download citation
DOI: https://doi.org/10.1007/978-1-4419-6418-2_14
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4419-6417-5
Online ISBN: 978-1-4419-6418-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)