Echocardiography in nonclinical studies: Where are we?

Abstract

Echocardiography is a powerful, noninvasive tool used both in clinical and nonclinical settings, including in drug development. When used appropriately, it can provide valuable translational information about pharmacodynamics, safety pharmacology, or toxicology, helping to define no-observed-adverse-effect levels and providing guidance for clinical monitoring and dose selection. Echocardiography is advantageous in conducting longitudinal studies and reducing the number of animals used in safety assessments. To this end, there has been no clear enunciation of what constitutes appropriate use of this imaging technology in a nonclinical drug development setting. In this review, we describe the use of echocardiography in nonclinical studies in regulatory submissions to the US Food and Drug Administration Center for Drug Evaluation and Research. In addition, we discuss three main areas: the operator, image acquisition, and image analysis, where variability may affect the reliability of information generated in an echocardiography study. As a path forward, our recommendation is for a multi-disciplinary expert working group to establish guidelines for education and credentialing of nonclinical echocardiographers as well as quality assurance standards for nonclinical echocardiography labs.