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The clinical practice of pharmaceutical medicine includes contributions from physicians, pharmacists, nurse practitioners, and physician assistants. Drug safety considerations are of considerable importance. This article discusses drug-induced proarrhythmia, with a specific focus on Torsade de Pointes (Torsade), a polymorphic ventricular tachycardia that typically occurs in self-limiting bursts that can lead to dizziness, palpitations, syncope, and seizures, but on rare occasions can progress to ventricular fibrillation and sudden cardiac death. A dedicated clinical pharmacology study conducted during a drug's clinical development program has assessed its propensity to induce Torsade using prolongation of the QT interval as seen on the surface electrocardiogram (ECG) as a biomarker. Identification of QT-interval prolongation does not necessarily prevent a drug from receiving marketing approval if its overall benefit-risk balance is favorable, but, if approved, a warning is placed in its Prescribing Information. This article explains why drugs can have a proarrhythmic propensity and concludes with a case presentation.

A Cardiac Safety Research Consortium / Health and Environmental Sciences Institute / FDA-sponsored Think Tank Meeting was convened in Washington, DC, on May 21, 2018, to bring together scientists, clinicians, and regulators from multiple geographic regions to evaluate progress to date in the Comprehensive In Vitro Proarrhythmia Assay (CiPA) Initiative, a new paradigm to evaluate proarrhythmic risk. Study reports from the 4 different components of the CiPA paradigm (ionic current studies, in silico modeling to generate a Torsade Metric Score, human induced pluripotent stem cell-derived ventricular cardiomyocytes, and clinical ECG assessments including J-Tpeakc) were presented and discussed. This paper provides a high-level summary of the CiPA data presented at the meeting.

Sample size estimation is the process by which a researcher decides how many subjects to include in a given clinical trial. Sample size estimation is a critical part of the design of clinical trials, and, like all design issues, this must be addressed in the study protocol before the trial commences. However, discussion of this topic was intentionally delayed until this point in the book so that you could read the intervening chapters and acquire an understanding of important concepts, including statistical significance and clinical significance, before reading about sample size estimation. Addressing sample size estimation at this point also allows a whole (short) chapter to be dedicated to this topic, thereby acknowledging its importance in clinical research.