Echocardiography in nonclinical studies: Where are we?

Area of Science:

• Cardiovascular imaging
• Pharmacology
• Drug Development

Background:

• Echocardiography is a noninvasive imaging technique with significant applications in clinical and nonclinical settings.
• Its utility in drug development includes assessing pharmacodynamics, safety pharmacology, and toxicology, aiding in dose selection and safety assessments.
• However, clear guidelines for its appropriate use in nonclinical drug development are lacking.

Purpose of the Study:

• To review the application of echocardiography in nonclinical studies submitted to the US Food and Drug Administration (FDA).
• To identify key areas of variability that may impact the reliability of echocardiography data in nonclinical drug development.
• To propose recommendations for standardizing nonclinical echocardiography practices.

Main Methods:

• Review of echocardiography use in regulatory submissions to the FDA's Center for Drug Evaluation and Research.
• Discussion of critical factors influencing data reliability: operator expertise, image acquisition protocols, and image analysis methodologies.
• Identification of variability sources in nonclinical echocardiography.

Main Results:

• Echocardiography provides valuable translational data for drug development, including safety and efficacy endpoints.
• Variability in operator skill, image acquisition, and analysis can compromise data integrity.
• Standardization is needed to ensure the reliability and reproducibility of nonclinical echocardiography studies.

Conclusions:

• Establishing clear guidelines for the education, credentialing, and quality assurance of nonclinical echocardiography is essential.
• A multi-disciplinary expert working group should be formed to develop these standards.
• Implementing standardized practices will enhance the translational value and regulatory acceptance of nonclinical echocardiography data.