Cardiac imaging approaches to evaluate drug-induced myocardial dysfunction.

The ability to make informed benefit-risk assessments for potentially cardiotoxic new compounds is of considerable interest and importance at the public health, drug development, and individual patient levels. Cardiac imaging approaches in the evaluation of drug-induced myocardial dysfunction will likely play an increasing role. However, the optimal choice of myocardial imaging modality and the recommended frequency of monitoring are undefined.

Electrocardiographic assessment for therapeutic proteins--scientific discussion.

Electrocardiographic monitoring is an integral component of the clinical assessment of cardiac safety of all compounds in development. The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use E14 guideline recommends a dedicated study to evaluate drug-induced effects on cardiac repolarization ("thorough QT/QTc study"). There has been limited published information on QT interval changes secondary to therapeutic proteins; however, in theory, biologic therapies may affect cardiac electrical activity either directly or indirectly.

Planning the Safety of Atrial Fibrillation Ablation Registry Initiative (SAFARI) as a Collaborative Pan-Stakeholder Critical Path Registry Model: a Cardiac Safety Research Consortium "Incubator" Think Tank.

Atrial fibrillation (AF) is a major public health problem in the United States that is associated with increased mortality and morbidity. Of the therapeutic modalities available to treat AF, the use of percutaneous catheter ablation of AF is expanding rapidly. Randomized clinical trials examining the efficacy and safety of AF ablation are currently underway; however, such trials can only partially determine the safety and durability of the effect of the procedure in routine clinical practice, in more complex patients, and over a broader range of techniques and operator experience.

Current challenges in the evaluation of cardiac safety during drug development: translational medicine meets the Critical Path Initiative.

In October 2008, in a public forum organized by the Cardiac Safety Research Consortium and the Health and Environmental Sciences Institute, leaders from government, the pharmaceutical industry, and academia convened in Bethesda, MD, to discuss current challenges in evaluation of short- and long-term cardiovascular safety during drug development. The current paradigm for premarket evaluation of cardiac safety begins with preclinical animal modeling and progresses to clinical biomarker or biosignature assays. Preclinical evaluations have clear limitations but provide an important opportunity to identify safety hazards before administration of potential new drugs to human subjects.