“Product Safety” Compromises Patient Safety (an Unjustified Black Box Warning on Ultrasound Contrast Agents by the Food and Drug Administration)

Abstract

a In October 2007, the United States Food and Drug Adinistration (FDA)1 issued an alert requesting “black-box” arnings on the perflutren-based ultrasound contrast agents efinity (Bristol-Myers Squibb Medical Imaging, North illerica, Massachusetts) and Optison (Amersham Health, mersham, UK). Additionally, the FDA recommended that hese agents “be contraindicated in patients with unstable ardiopulmonary status, including patients with unstable ngina, acute myocardial infarction (MI), respiratory failre, or recent worsening congestive heart failure.” Accordng to the FDA’s Web site, there have been postmarketing eports of 10 deaths after the administration of Definity and after the administration of Optison. At least 6 of these ccurred 1 to 12 hours after dosing and were attributed to erious underlying conditions and/or other medications. our fatal cases, however, occurred 30 minutes after the dministration of Definity: 1 after a stress test, 2 in patients ith severe heart failure, and 1 in a ventilated patient with evere respiratory failure, sepsis, and multiple pulmonary mboli. These 4 deaths occurred over a 6-year period. Durng that period, 2 million doses were administered (Brisol-Myers Squibb Medical Imaging, personal communicaion). Thus, the fatal event rate was approximately 1 in 00,000. This rate is far less than the fatal event rate of a readmill exercise test (1 in 2,500)2 or a transesophageal chocardiogram (1 in 10,000).3 In fact, this extremely low vent rate testifies to the safety of these agents, considering hat they are frequently used in critically ill patients. It is lmost certain that the 4 fatal cases were consequences of evere underlying cardiovascular disease and were not aused by the contrast agent.4 According to the FDA’s Web site, the FDA “has the reponsibility for assuring the safety and efficacy of all regulated arketed medical products.” Product safety is not the same as atient safety. The FDA is concerned with whether a regulated rug or medical device has a potential adverse safety profile. hus, the FDA focuses on the term “product safety.” Patient afety lies within the domain of the physician-patient relationhip and is not the concern of the FDA. For example, consider he case of an elderly, debilitated patient with symptomatic, evere aortic stenosis. After extensive evaluation, her cardiolgist determines that although aortic valve replacement with an DA-approved bioprosthesis would relieve the aortic stenosis,