Over 10 years, nearly 10% of all serious, or previously unlisted, adverse events, and more than 40,000 drug reactions resulting in the death of a patient, were not reported by drug manufacturers to the FDA within the 15-day requisite window, researchers reported.
Out of 1,613,079 adverse event reports in the FDA’s tracking system, 90.06% were reported in a timely fashion, but the remaining 9.94% took anywhere from 16 days to over 180 days to be submitted, and those delayed reports were more likely to involve a patient death than adverse events reported during the appropriate threshold of 15 days, Paul Ma, PhD, of the University of Minnesota, and colleagues, reported in a research letter in JAMA Internal Medicine.
“Such reporting delays should never occur, as they mean that more patients are exposed to potentially avoidable serious harm, including death,” Rita F. Redberg, MD, MSc, of the University of California San Francisco, wrote in an editorial in JAMA Internal Medicine. “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.”
Redberg suggested an enforcement tool the FDA could immediately deploy: “suspending drug sales or withdrawing drug approval.” She also suggested streamlining the process so that adverse events could be reported directly to the FDA as opposed to going through the manufacturer, a recommendation also made by Ma and colleagues.
“This would address the delay problem, although additional efforts to make the data available and take appropriate actions are still necessary,” Redberg wrote. “Physicians and their patients must be knowledgeable of benefits, harms, and alternatives for a wide choice of treatments, especially those recently approved for which clinical experience is limited.”
Standard side-effects in accordance with those listed on a medication’s label don’t have to be reported to the FDA. However, serious adverse events resulting in a patient being admitted to the hospital, or causing a congenital anomaly in offspring, must be reported to the FDA. Unexpected adverse events, any side effect not listed in the current labeling of the drug, must also be reported.
These reports must be filed by the drug maker “‘as soon as possible but in no case later than 15 calendar days of the initial receipt of the information.'” the authors referenced the FDA.
Ma’s team looked at quarterly data from the FDA adverse event reporting system from 2004 to 2014. Only about 5% of those reports were direct from patients, which Ma’s team removed from the analysis in order to focus on the actions of drug manufacturers.
The researchers categorized reports as occurring within the 15-day requisite window, and by from time frames after the patient’s healthcare provider reported the event to the drug maker, 16-90 days, 91 to 180 days, or more than 180 days.
Overall, they included 1,613,079 adverse event reports, of which 160,383, or 9.94%, were not submitted within the 15-day threshold. Out of those, 40,464 involved a patient death.
“Strikingly, AEs [adverse events] with patient death were more likely to be delayed,” the authors wrote.
Ma’s team reported that more adverse events without patient death were reported to the FDA within the 15-day window compared to those with patient death, 90.71% versus 88.25%, respectively (difference -2.46%).
But, after the 15-day window, adverse event reporting was more likely to include patient deaths. In the 16 to 90 day window, 6.42% of events had a patient death, and 5.19% of events did not (difference 1.23%). For the 91 to 180 day window, 2.53% included patient deaths compared with 1.98% that did not, representing a difference of 0.55%.
Ha and colleagues suspected that their findings were likely an underestimate of underreporting or misreporting, “given the anecdotal evidence of FDA warning letters to manufacturers alleging downward misclassification of serious AEs [adverse events].”
The authors argued that healthcare professionals should begin directly reporting adverse events to the FDA, bypassing initial reports to the drug maker.
None of the authors reported any relevant financial relationships with industry.
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