Drug Manufacturers’ Delayed Disclosure of Serious and Unexpected Adverse Events to the US Food and Drug Administration

Federal regulations define adverse drug events as those “associated with the use of a drug in humans whether or not considered drug related”. Health care professionals and consumers can voluntarily report adverse drug events directly to the US Food and Drug Administration (FDA) or the drug manufacturer. Serious adverse events (AEs) are defined by the regulation as those involving “death, a life-threatening adverse drug experience, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect.” Unexpected AEs are defined as those involving “any adverse drug experience that is not listed in the current labeling for the drug product.” Serious and unexpected events are classified as expedited, and manufacturers receiving any such reports are mandated to forward them to the FDA “as soon as possible but in no case later than 15 calendar days of the initial receipt of the information.” The regulation also requests that the manufacturer conduct an investigation and forward findings as follow-up reports to the FDA. Previous studies highlighted that reports by manufacturers to the FDA of serious adverse drug events have increased steadily during the past decade. Manufacturer compliance with the regulation to report serious and unexpected AEs to the FDA within 15 calendar days is unknown, although some media coverage has offered anecdotal examples of delays. As the FDA uses this information to update drug warnings, delays in reporting can have important public health consequences, particularly if manufacturers selectively delay reporting based on relevant patient outcomes. We investigated patient and event characteristics associated with manufacturers’ delayed submission of the expedited reports to the FDA.