Concerns Raised Regarding Delays in Mandatory Drug Death Reporting
One in every 10 serious adverse drug events, including deaths, was not reported to the FDA within regulation timelines.
Drug manufacturers delayed reporting serious adverse drug events in the last decade in nearly one of every 10 cases, according to reports submitted to the U.S. Food and Drug Administration (FDA) published online ahead of print in JAMA.
Kaplan-Meier estimates of nearly 1.6 million adverse events (AEs) determined that the FDA did not receive nearly 10% of the required documents within the mandatory 15-day window, a total of 160,383, of which 40,464 involved patient deaths.
“Strikingly,” the authors noted, “AEs with patient death were more likely to be delayed.”
The study's authors—Paul Ma, PhD, of the University of Minnesota Carlson School of Management in Minneapolis MN; Pinar Karaca-Mandic, PhD, of the university's Division of Health Policy and Management in the School of Public Health; and Ivan Marinovic, PhD, of Stanford University's Graduate School of Business, in Stanford CA,—found that nearly half of the delayed reports were received more than 90 days late.
And that, they wrote, probably missed an untold number.
“Our findings are likely an underestimate of overall underreporting or misreporting, given the anecdotal evidence of FDA warning letters to manufacturers alleging downward misclassification of serious adverse events.”
Timely reporting is important because the FDA uses this information to update drug warnings and a delay has important implications for patient safety.
“Interestingly, these were not just a few days of delay, and that to me personally was very surprising,” said Karaca-Mandic in a telephone interview with Cancer Therapy Advisor.
“If we had just a few days of delay then it would be harder, maybe, to argue that this would have important safety implications. But what we were finding is that about 6% of these reports were recorded within the 16- to 90-day window, but 6% were delayed even further. So these are important delays.”
The paper's authors suggested that it is possible for manufacturers to spend additional time in verifying reports concerning deaths, “but this discretion is outside the scope of the current regulatory regime.”
A stern editor's note accompanying the paper called for stricter measures to compel compliance.
“Such reporting delays should never occur, as they mean that more patients are exposed to potentially avoidable serious harm, including death,” wrote JAMA Internal Medicine's chief editor, Rita F. Redberg, MD, MSc.
“However, no disciplinary actions have been taken when companies fail to submit reports to the FDA in the time frame required. Clearly, the lack of consequences contributes to a lack of deterrence for these illegal and dangerous delays.”
She suggested the FDA consider a tough regulatory option.
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“There is another enforcement tool that the FDA could begin to deploy immediately: suspending drug sales or withdrawing drug approval.”
The authors suggested that one possible solution might be achieved by encouraging direct reporting by doctors, hospital administrators, and other health officials, thereby circumventing manufacturer involvement in the initial report process.
That way, Karaca-Mandic said, the FDA could update its database even as manufacturers continue their private investigations into events.
- Ma P, Marinovic I, Karaca-Mandic P. Drug manufacturers' delayed disclosure of serious and unexpected adverse events to the US Food and Drug Administration. [published online ahead of print July 27, 2015] JAMA Intern Med. doi:10.1001/jamainternmed.2015.3565.