Pediatric contrast-enhanced ultrasound: shedding light on the pursuit of approval in the United States

Abstract

For two decades, pediatric contrast US has been well accepted throughout Europe and other parts of the world outside the United States because of its high diagnostic efficacy and extremely favorable safety profile. This includes intravenous (IV) administration, contrast-enhanced US (CEUS) and the intravesical application, contrast-enhanced voiding urosonography (ceVUS). However, the breakthrough for pediatric contrast US in the United States did not come until 2016, when the U.S. Food and Drug Administration (FDA) approved the first pediatric indication for a US contrast agent. This initial approval covered the use of Lumason (Bracco Diagnostics, Monroe Township, NJ) for the evaluation of focal liver lesions via IV administration in children. A second pediatric indication followed shortly thereafter, when the FDA extended the use of Lumason for assessing known or suspected vesicoureteral reflux via intravesical application in children. Both initial pediatric approvals were granted without prospective pediatric clinical trials, based instead on published literature describing favorable safety and efficacy in children. Three years later, in 2019, the FDA approved Lumason for pediatric echocardiography following a clinical trial involving a total of 12 subjects at 2 sites. The story of how we achieved these FDA approvals spans more than a decade and involves the extraordinary dedication of two professional societies, namely the International Contrast Ultrasound Society (ICUS) and the Society for Pediatric Radiology (SPR). Credit also must be given to the FDA staff for their commitment to the welfare of children and their openness to compelling evidence that contrast US is a safe, reliable, radiation-free imaging option for our pediatric patients. Understanding the history of this approval process will impact the practical application of US contrast agents, particularly when expanding off-label indications in the pediatric population. This article describes the background of the FDA's approval of pediatric contrast US applications to better illuminate the potential pathways to approvals of future indications.

Keywords: Children; Drug approval; International Contrast Ultrasound Society; Legislation; Lumason; Society for Pediatric Radiology; Ultrasound; Ultrasound contrast agent; United States Food and Drug Administration.