Chapter 8
Cardiovascular toxicity, especially QT/QTc prolongation
Arne Ring Ph.D.,
Robert Schall Ph.D.,
Arne Ring Ph.D.
Leicester Clinical Trials Unit, University of Leicester, LE5 4PW, UK
Department of Mathematical Statistics and Actuarial Science, University of the Free State, 205 Nelson Mandela Drive, Bloemfontein, 9301, South Africa
Search for more papers by this authorRobert Schall Ph.D.
Department of Mathematical Statistics and Actuarial Science, University of the Free State, 205 Nelson Mandela Drive, Bloemfontein, 9301, South Africa
Quintiles Biostatistics, Bloemfontein 9301, South Africa
Search for more papers by this authorArne Ring Ph.D.,
Robert Schall Ph.D.,
Arne Ring Ph.D.
Leicester Clinical Trials Unit, University of Leicester, LE5 4PW, UK
Department of Mathematical Statistics and Actuarial Science, University of the Free State, 205 Nelson Mandela Drive, Bloemfontein, 9301, South Africa
Search for more papers by this authorRobert Schall Ph.D.
Department of Mathematical Statistics and Actuarial Science, University of the Free State, 205 Nelson Mandela Drive, Bloemfontein, 9301, South Africa
Quintiles Biostatistics, Bloemfontein 9301, South Africa
Search for more papers by this authorBook Editor(s):A. Lawrence Gould,
A. Lawrence Gould
Merck Research Laboratories, 770 Sumneytown Pike, West Point, PA 19486, USA
Search for more papers by this authorFirst published: 12 December 2014
Summary
The cardiovascular safety of drugs has always been an important aspect of drug development. In the assessment of QT interval prolongation, an effect of the drug on the QT interval as such must be distinguished from an effect of the drug on the QT interval that is explained by the drug's effect on the heart rate. This chapter discusses the statistical methods that can make this distinction. It outlines how assessments of QT prolongation can be implemented in clinical drug development. The chapter also describes the design of “thorough QT” (TQT) trials, and discusses practical examples from the literature. It focuses on healthy volunteer trials with non-cytotoxic drugs. It finally discusses a number of trial designs and analyses that have been performed. These examples provide insight into typical options and considerations when planning new TQT trials.
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