TY - JOUR AU - Begosh,Allan AU - Goldsmith,John AU - Hass,Ed AU - Lutter,Randall W. AU - Nardinelli,Clark AU - Vernon,John A. TI - Black Box Warnings and Drug Safety: Examining the Determinants and Timing of FDA Warning Labels JF - National Bureau of Economic Research Working Paper Series VL - No. 12803 PY - 2006 Y2 - December 2006 UR - http://www.nber.org/papers/w12803 L1 - http://www.nber.org/papers/w12803.pdf N1 - Author contact info: Allan Begosh Suite 15-36 Office of the Commissioner Food and Drug Administration 5600 Fishers Lane Rockville, MD 20857 E-Mail: allan.begosh@FDA.gov John Goldsmith Suite 15-36 Office of the Commissioner Food and Drug Administration 5600 Fishers Lane Rockville, MD 20857 E-Mail: jcgoldsm@erols.com Ed Hass Suite 15-36 Office of the Commissioner U.S. Food and Drug Administration 5600 Fishers Lane Rockville, MD 20857 E-Mail: Ed.Hass@FDA.HHS.GOV Randall Lutter Suite 15-36 Office of the Commissioner Food and Drug Administration 5600 Fishers Lane Rockville, MD 20857 E-Mail: Rlutter@oc.fda.gov Clark Nardinelli Suite 15-36 Office of the Commissioner Food and Drug Administration 5600 Fishers Lane Rockville, Maryland 20857 E-Mail: Clark.Nardinelli@FDA.HHS.GOV John Vernon University of North Carolina at Chapel Hill Department of Health Policy & Management 1101C McGavran-Greenberg Hall Chapel Hill, NC 27599-7411 Tel: 919/966-8930 E-Mail: vernon@email.unc.edu AB - Comparing the safety of prescription drugs over time is difficult due to the paucity of reliable quantitative measures of drug safety. Both the academic literature and popular press have focused on drug withdrawals as a proxy for breakdowns in the drug safety system. This metric, however, is problematic because withdrawals are rare events, and they may be influenced by factors beyond a drug's safety profile. In the current paper, we propose a new measure: the incidence and timing of Black Box Warnings (BBWs). BBWs are warnings placed on prescription drug labels when a drug is determined to carry a significant risk of a serious or life-threatening adverse event. Using a unique data set, one that includes all new molecular entities (NMEs) submitted to the FDA between May 1981 and February 2006, and subsequently approved and marketed, we analyze the timing and incidence of BBWs. Our analyses also use data on several drug characteristics likely to affect the probability a new drug will receive a BBW. We draw several conclusions from our analyses. For example, drugs receiving priority FDA review are more likely to have BBWs at the time of approval than NMEs receiving standard review. We also find that early prescription volume and orphan drug status are associated with an increased likelihood of receiving a BBW. We do not, however, find a significant difference in the rate of BBWs across time cohorts. A comparison of NMEs approved before and after the 1992 Prescription Drug User Fee Act (PDUFA), which authorized the payment of user fees from drug manufacturers to the FDA in an effort to expedite new drug application (NDAs) review times, did not reveal a statistically significant difference in the rate of BBWs. Critics of PDUFA maintain that reduced FDA-approval times under PDUFA have compromised drug safety. We do not find empirical support for this contention. ER -