Study: Drug manufacturers delay reporting serious adverse events to the FDA

Monday, July 27, 2015

A new study published today found drug manufacturers delay reporting serious and unexpected adverse events to the U.S. Food and Drug Administration (FDA). In particular, adverse events with a patient death were more likely to be delayed relative to non-death outcomes.

The research was published in JAMA Internal Medicine and was a partnership between the University of Minnesota and Stanford Graduate School of Business.

Federal regulations define adverse events as those “associated with the use of a drug in humans whether or not considered drug related.”  The Federal regulation requires that reports for serious and unexpected adverse events received by the manufacturers have to be reported to the FDA within 15 calendar days. The study examined such reports subject to the 15-day rule for the period of January 2004 through June 2014.

Pharmaceutical companies have long been accused of withholding important safety information as evidenced by FDA warning letters and recent media coverage. This report is the first study to systematically find evidence for delayed reporting of adverse events to the FDA, especially for events that involve a patient death.

The study was co-authored by Pinar Karaca-Mandic, Ph.D., associate professor of health policy management in the School of Public Health at the University of Minnesota, Ivan Marinovic, Ph.D., assistant professor of accounting at the Stanford Graduate School of Business and Paul Ma, Ph.D., assistant professor of accounting in Carlson School of Management at the University of Minnesota.

“Our findings are even more concerning because they are likely an underestimate of the overall underreporting or misreporting of serious or adverse events,” said Karaca-Mandic. “Our study analysis is limited to the events that are reported to the FDA and there could be cases in which drug manufacturers fail to report serious or unexpected events at all by downward classifying serious reports as non-serious.”

Furthermore, the authors conclude that if the drug manufacturer does not accurately report the date it received the report then the true fraction of delayed events will also be underestimated.

Timely reporting of adverse events is crucial to the FDA because they use this information to update drug warnings and these delays could potentially have important public health consequences.

"Our study suggests that direct submission of reports to the FDA, in lieu of submitting to an intermediary such as the drug manufacturer, may help reduce reporting delays,” said Ma. “While it is possible that drug manufacturers spend additional time in verifying reports with more serious patient outcomes – the delays are not just by a few days, but can be several months or years. Future research is needed to help understand the mechanisms behind the drug manufacturer’s decision to delay which could help policymakers such as the FDA in determining the optimal reporting rule.”