Inside the black box: current policies and concerns with the United States Food and Drug Administration's highest drug safety warning system

A Special Authors Introduction

By Paul Barash

The United States Food and Drug Administration (FDA) regulates goods accounting for twenty-five cents ($ 0.25) of every dollar spent by American consumers. One of the primary areas of responsibility is oversight of pharmaceuticals. As the watchdog for drug safety, the FDA uses a variety of methods to promote this objective. The black-box warning (BBW) is the highest level of warning promulgated by the agency. The BBW is used in three situations: (1) serious life-threatening adverse reactions, (2) the risk of a serious adverse event can be reduced by appropriate patient selection, withholding use of drug in certain clinical situations, laboratory monitoring, etc and (3) FDA approval is accompanied by restrictions on use and distribution. Although a laudable effort to decrease risk of pharmacologic treatment, the process of affixing a BBW to a given drug: (1) is subjective, (2) lacks a standardized protocol to identify high-risk drugs, and (3) does not require peer review. This procedure can lead inequities in applying BBWs in a universal and consistent fashion.

The use of BBW for droperidol is a case in point. In 2001, 31 years after the introduction of droperidol into clinical practice, the FDA issued a BBW for its use based upon reports of prolongation of the QT interval and the development of Torsades de Pointes. However, detailed expert analysis of the FDA data behind this decision does not appear to support applying a BBW to droperidol. The BBW for this drug resulted in marked decrease in its use for postoperative nausea and vomiting (PONV), causing clinicians to switch to more expensive alternatives with similar risk profiles. A consensus panel on the management of PONV stated that if it were not for BBW, droperidol would be the panel's primary choice for prophylaxis and treatment of this complication.

In conclusion, the use of BBW system to alert clinicians to complications related to high-risk drugs is meritorious. However, at present, significant limitations in its application and use render the BBW less potent as a means of improving drug safety.

This article was published in Current Opinion in Anesthesiology
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