News | Ultrasound Imaging | March 07, 2019

Ultrasound Societies Urge FDA to Remove Black Box Warning on Echo Contrast Agents

Citizen petition argues that current research has demonstrated ultrasound contrast agents safe and effective

Ultrasound Societies Urge FDA to Remove "Black Box" on Ultrasound Contrast Agents

March 7, 2019 — National and international ultrasound societies are urging the U.S. Food and Drug Administration to remove the “black box” from ultrasound contrast agent (UCA) labels.

“UCAs are among the safest diagnostic imaging products available,” according to a citizen petition filed by the International Contrast Ultrasound Society (ICUS).

UCAs are used worldwide to enhance diagnostic ultrasound scans, according to the petition, which cited an extensive body of favorable safety data that was not available in 2007 when the boxed warnings were first mandated by the FDA.

“It is clear to all who work in the field on a daily basis that the black box harms patient care by misrepresenting risk and inappropriately deterring the use of UCAs when they are medically indicated,” said Steven Feinstein, M.D., co-president of ICUS and professor of medicine at Rush University Medical Center in Chicago. “There is now a strong consensus from across the adult and pediatric medical ultrasound community that ultrasound contrast agents are extremely safe and do not warrant boxed warnings,” he added.

Medical societies supporting the ICUS Petition include:

  • The American Institute of Ultrasound in Medicine (AIUM);
  • The World Federation of Ultrasound in Medicine and Biology (WFUMB);
  • The Society of Radiologists in Ultrasound (SRU);
  • The Society of Diagnostic Medical Sonography (SDMS);
  • The Society for Pediatric Radiology (SPR);
  • The American Society of Echocardiography (ASE); and
  • The Liver Imaging Reporting and Data System (LI-RADS) contrast-enhanced ultrasound (CEUS) working group.

Numerous individual physicians also submitted letters supporting the ICUS petition.

“We are disappointed that ‘black box warnings’ are still mandated for ultrasound contrast agents, despite extensive scientific research and practice demonstrating their safety,” according to Brian Coley, M.D., AIUM president, professor of medicine and radiologist-in-chief at Cincinnati Children’s Hospital.

According to the ICUS Petition, UCAs are injected into a patient’s arm vein during a diagnostic ultrasound scan to help diagnose heart disease, pinpoint and characterize cancers, monitor chronic gastro-intestinal diseases, detect vascular disease, evaluate other serious medical conditions and monitor therapy. By improving the reliability of real-time ultrasound scans, UCAs often reduce the need for unnecessary downstream tests and related costs, speed up the time to diagnosis and access to appropriate therapy, reduce the length of hospital stays, and improve patient care, outcomes and experiences.

UCAs do not contain radioactive material or dye, present no known risk of kidney or liver damage, and do not require sedation. The agents are metabolized and expelled from the body, primarily through the lungs, within minutes.

“Our collective experience shows that UCAs are exceedingly safe and beneficial, and they can change patient outcomes and improve patient experiences,” according to a statement submitted by the SRU on behalf of American radiologists with expertise in ultrasound.

The SRU statement added that CEUS is often “equivalent to or superior to CT [computed tomography] and MRI [magnetic resonance imaging], yet it is less expensive, more patient-friendly, more widely available and completely radiation-free.”

According to the ICUS Petition, a “black box” warning is appropriate only as an indicator of the very highest level risk associated with FDA-approved products, and studies now show “no increased safety signal even among the sickest patients.” The petition describes safety studies undertaken after 2007 at the request of the FDA, as well as other independent studies recently published in peer-reviewed journals.

"The data now clearly and consistently show that UCAs are extremely safe — even in the sickest patients,” according to Michael Main, M.D., a cardiologist at Saint Luke’s Mid America Heart Institute in Kansas City. Main is a vice president of ICUS and the principal author of recent studies examining the safety of UCAs.

Richard Barr, M.D., a radiologist in Youngstown, Ohio, wrote that his physician group has used CEUS in more than 3,000 patients over more than 10 years, without a single significant adverse event. Barr is also the editor-in-chief of the Journal of Ultrasound in Medicine and stated that he supports the ICUS petition.

In addition, Barr said that CEUS prevented a large number of biopsies and surgeries, and allowed his group to confirm benign lesions with confidence and detect other lesions at an earlier stage so that appropriate therapy could be provided more quickly. He noted that CEUS is also an important tool for patients who are unable to tolerate contrast CT or MR, such as patients with kidney insufficiency.

CEUS also offers a “huge advantage” for pediatric patients, according to Kassa Darge, M.D., Ph.D., radiologist-in-chief at Children’s Hospital of Philadelphia. He said CEUS can reduce or eliminate radiation exposure, avoid sedation or anesthesia, avoid gadolinium contrast deposits — and ultimately is “much more sensitive or depicts the pathology clearer” in many pediatric ultrasound scans.

Darge said that the “high safety profile” of CEUS in children has now been documented in scientific publications encompassing thousands of children, and there are “no real scientific reasons for having this label.”

Yet because of the black box, some physicians are unduly reluctant to refer patients for CEUS and some patients are apprehensive about receiving UCAs, according to Barr and other experts who weighed in on the petition.

“The unnecessary presence of a black box results in unfounded fears of utilization of these extremely beneficial agents, and patients are thus exposed to potentially more harmful investigative procedures, or worse, have no information due to uninterpretable, or misinterpreted ultrasound studies, resulting in missed or wrong diagnoses,” according to Sharon Mulvagh, M.D., professor of medicine emeritus, Mayo Clinic in Rochester, Minn., and professor of medicine, Dalhousie University in Halifax, Canada.

Watch the VIDEO: Use of Ultrasound to Assess Heart Disease Risk, an interview with Mulvagh at ASE 2017.

“The Black Box serves no useful purpose,” according to a letter submitted by Yuko Kono, M.D., clinical professor of medicine and radiology at the University of California, San Diego; Stephanie Wilson, M.D., clinical professor of radiology and medicine at the University of Calgary; and Andrej Lyshchik, M.D., Ph.D., associate professor of radiology at Thomas Jefferson University Hospital in Philadelphia. Kono, Wilson and Lyshchik are members and chair of the CEUS LI-RADS Working Group.

According to Wilson, the United States is behind the rest of the world when it comes to using CEUS, which she described as a very patient-friendly, extremely reliable and easy-to-use imaging tool.

“We believe the boxed warning is not warranted and only discourages the use of CEUS,” according to Beth McCarville, M.D., and Peter Strouse, M.D., writing on behalf of SPR, the pediatric radiology organization. According to them, a growing body of literature now validates the excellent safety profile of UCAs, which offer a “safe, sedation-free and radiation-free, low-risk method of assessing a variety of conditions in children and should be embraced and supported by pediatric care providers.”

The ICUS petition notes that the FDA has steadily responded to the mounting evidence of UCA safety and efficacy by downgrading package insert contraindications three times since 2007, and removing a 30-minute monitoring requirement for patients with pulmonary hypertension or unstable cardiopulmonary conditions. More recently, the FDA approved new indications for use in adults and children.

Three UCAs are currently approved for use in the United States — Definity (Lantheus Medical Imaging), Lumason (Bracco) and Optison (GE Healthcare).

For more information: www.icus-society.org

 

Related Echo Contrast Content:

The Status and Future of Contrast Echocardiology

Recent Developments and Issues in Contrast Media

Watch the VIDEO: Therapeutic Applications for Contrast Ultrasound

Micro-Bubble Echo Contrast Procedures Rebounded in 2008

Busting Blood Clots in the Ambulance

Ultrasound-Activated Bubbles Aid Clot-Busters

Study Demonstrates Strain Imaging Utility With Contrast-Echo Studies

Study Says Usage of Ultrasound Contrast Agents in Echocardiography Declined

Ultrasound-activated Microbubbles Restore Blood Flow During Heart Attack

Trends and Advances in Echocardiography at ASE 2015

Related Content

EchoGo Pro automates cardiac ultrasound measurements for heart functions, but also empower physicians to predict the occurrence of coronary artery disease (CAD).

EchoGo Pro automates cardiac ultrasound measurements for heart functions, but also empower physicians to predict the occurrence of coronary artery disease (CAD).

News | Cardiovascular Ultrasound | September 25, 2020
September 25, 2020 — Based on its recent analysis of the global...
The Epiq CVxi being used for TEE imaging in the cath lab. The system brings together advanced image quality, quantification and intelligence specifically for the cardiologist.

The Epiq CVxi being used for TEE imaging in the cath lab. The system brings together advanced image quality, quantification and intelligence specifically for the cardiologist.

News | Cardiovascular Ultrasound | September 15, 2020
September 15, 2020 — Philips Healthcare recently introduced the latest addition to its portfolio of dedicated...
GE Healthcare Vscan with artificial intelligence (AI) automated left ventricular ejection fraction assessment with the Dia LVivo EF app. #ASE2020

GE Healthcare Vscan with artificial intelligence (AI) automated left ventricular ejection fraction assessment with the Dia LVivo EF app.

News | Cardiovascular Ultrasound | August 12, 2020
August 12, 2020 — GE focused on the latest innovations from the handheld ultrasound,...
TomTec offers innovations in cardiac ultrasound, including AI and auto quanitification of echo images.

TomTec offers innovations in cardiac ultrasound, including AI and auto quanitification of echo images.

News | Cardiovascular Ultrasound | August 04, 2020
August 4, 2020 — Imaging software company TomTec has released its new TomTec-Arena 2020 product, which offers new adv
Judy Hung, M.D., speaking with DAIC Editor Dave Fornell during a video interview at the 2019 American Society of Echocardiography (ASE) annual meeting. Hung took over as ASE President in June.

Judy Hung, M.D., speaking with DAIC Editor Dave Fornell during a video interview at the 2019 American Society of Echocardiography (ASE) annual meeting. Hung took over as ASE President in June.

News | Cardiovascular Ultrasound | July 09, 2020
July 8, 2020 – Judy W.
A Philips Healthcare transesophageal echocardiography (TEE) system in use in a hybrid OR.

A Philips Healthcare transesophageal echocardiography (TEE) system in use in a hybrid OR.

News | Cardiovascular Ultrasound | June 04, 2020
June 4, 2020 — Intra-operative...