A Cardiovascular and Renal Drugs Advisory Committee to the FDA held a public meeting last week to discuss safety considerations in the development of ultrasound contrast agents. Briefing information from the FDA found here.
The meeting comes in the midst of litigation concerning this important type of medical product. For example, about 70 cases have been filed in more than a dozen jurisdictions alleging that gadolinium-based injectable contrast agents cause serious health problems. Plaintiffs claim that gadolinium in contrast solutions used in magnetic imaging causes Nephrogenic Systemic Fibrosis. The federal suits were consolidated in February into an MDL in the U.S. District Court for the Northern District of Ohio. IN RE: GADOLINIUM BASED CONTRAST AGENTS PRODUCTS LIABILITY LITIGATION, MDL No. 1909. The parties made science presentations to the the Court in April, 2008.
Representatives for the makers told panelists this week that the agents are not unduly unsafe and noted that many patients given the agents are already very sick. A number of physicians speaking to the panel urged further study, but said medical information gathered through use of the contrast agents outweighed their side effects. The agents give life-saving information.
Ultrasound contrast agents are “microbubble” (or “microsphere”) drugs that are injected into the vascular system in order to improve the diagnostic information obtained from ultrasound-based images. The ultrasound contrast agents approved by the FDA are used in ultrasounds, such as echocardiography, and assist in the diagnosis of various conditions. The uniqueness of the physical and chemical properties of the ultrasound contrast agents, the technicalities of the ultrasound field and its rapid technical advances, combined with the unique design considerations for clinical studies of diagnostic imaging agents have all presented special challenges in the clinical development and optimal use of these agents.
The advisory committee was created to provide a public forum for review of the history of the currently marketed ultrasound contrast agents, to obtain opinions from the advisors regarding safety considerations in the development of these agents, and to begin to familiarize the committee members with the review of diagnostic imaging agents.
According to the FDA, post-marketing reports and new animal data prompted label changes for certain of these products in October, 2007. These changes included a black-box warning and contraindication for use of the products in certain patients with underlying cardiopulmonary conditions.
FDA has most recently been working with the manufacturers to develop a risk assessment and management program. In addition to physician education and enhanced oversight of clinical studies, this program consists of two studies. One is an observational study to be conducted using an administrative database in which mortality will be compared between critically ill patients who receive a contrast-enhanced echocardiogram and critically ill patients who undergo echocardiography without contrast. The second study will obtain pulmonary hemodynamic data from patients who are undergoing right heart catheterization as well as contrast-enhanced echocardiography.