title: Ethical and Practical Considerations in Removing Black Box Warnings from Drug Labels.
abstract: Boxed warnings-also known as "black box" warnings-can be a powerful tool in communicating drug risks to physicians and patients. The overall number of boxed warnings has grown in recent years as the US Food and Drug Administration (FDA) has approved more drugs on the basis of limited pre-marketing information and as new safety issues for marketed drugs have been identified. Two recent manufacturers' petitions to remove boxed warnings on the drugs rosiglitazone (Avandia) and varenicline (Chantix) have led to divergent FDA decisions and revealed different considerations involved in boxed warning imposition and removal. For ethical and practical reasons, the FDA is justified in applying a higher standard for boxed warning removal than for imposition, as removal of a boxed warning may have unintended effects on physician and patient behavior. However, no guidelines on boxed warning removal currently exist. To promote safe use of approved prescription drugs, the FDA should adopt a uniform and transparent process governing decisions to impose or remove boxed warnings.
authors.affiliation: Program on Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 1620 Tremont Street, Suite 3030, Boston, MA, 02120, USA. jsyeh@partners.org.
authors.forename: James S
authors.identifier: 0000-0003-3549-6096
authors.initials: JS
authors.lastname: Yeh
authors.affiliation: Program on Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 1620 Tremont Street, Suite 3030, Boston, MA, 02120, USA.
authors.forename: Ameet
authors.initials: A
authors.lastname: Sarpatwari
authors.affiliation: Program on Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 1620 Tremont Street, Suite 3030, Boston, MA, 02120, USA.
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Kesselheim
mesh_terms: D017277:Drug Approval; D004345:Drug Industry; D004348:Drug Labeling / Q000941:ethics / Q000331:legislation & jurisprudence*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000517:prevention & control; D006801:Humans; D007880:Legislation, Drug; D055553:Prescription Drugs / Q000008:administration & dosage / Q000009:adverse effects*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000009:adverse effects; D014481:United States; D014486:United States Food and Drug Administration; D000068580:Varenicline / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D055553:Prescription Drugs; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000068580:Varenicline