Almost 1 in 10 serious adverse events linked to consumer medications are not reported promptly by drug manufacturers to the U.S. Food and Drug Administration, a University of Minnesota researcher reported Monday.
Drug companies are required to file reports with the FDA within 15 days when notified that their products were associated with serious or unexpected harm to patients, including death and disability. But the U's Pinar Karaca-Mandic and colleagues found that companies frequently fall short — especially when the incidents involve deaths — a finding that suggests serious gaps in federal drug-safety regulation.
"FDA uses the [reporting system] to monitor drug safety and to timely update drug warnings," Karaca-Mandic said. "This is why delays in reporting could have important consequences for patient safety."
The researchers analyzed 1.6 million adverse-event reports provided to the FDA between 2004 and 2014 regarding medications. Of that group, 160,383 were filed beyond the mandatory 15-day reporting window, including 40,464 reports that involved a patient death.
Karaca-Mandic said she was surprised by the length of delay in some of the fatality cases; 3 percent were reported within three to six months, and another 3 percent took six months or longer to report.
While new drugs are tested in animal and human clinical trials before federal approval, unexpected side effects can emerge once medications are used by a larger population.
An individual, unproven report of a medication side effect might not concern authorities, but a series of such reports to the federal database often prompts closer scrutiny of a medication.
Earlier this month, for example, the FDA raised concerns about a medication to control blood sugar after reviewing adverse-event reports that suggested it can cause high blood pressure in newborns and infants. Adverse-event reports since 2013 for certain antidepressants have prompted the FDA to monitor them for glaucoma risks, and have prompted the addition of heart attacks and death as potential side effects on the packaging for two drugs used in cardiac stress tests.
Why lags can occur
The reporting requirement starts when manufacturers are notified by doctors, pharmacists or patients of adverse events, which include hospitalizations, disabilities or birth defects potentially caused by prescription or over-the-counter medications.
Unexpected events are defined as problems that aren't listed in the federally approved warning labels on medications and are subject to the 15-day reporting requirement as well.
Manufacturers must report adverse events regardless of whether there is proof that a drug was the cause of patient harm.
Still, they are required to do some basic investigation, and that can cause delays in the filing of a report, said a spokesperson from PhRMA, the trade group that represents drug companies.
"Companies typically verify the accuracy of patient and physician reports and often contact adverse-event reporters to supplement the information that they provide to the FDA," the spokesperson said in an e-mailed statement.
The FDA can fine drugmakers that fail to comply with reporting requirements, and can restrict or withdraw drug approvals in extreme cases, though that is rare.
Karaca-Mandic, an associate professor in the U's School of Public Health, and colleagues published their findings in a medical journal, JAMA Internal Medicine. Further research could yield additional findings, such as whether certain manufacturers or types of drugs are more likely to be involved in delayed reporting.
A similar FDA reporting system exists for medical devices, and Karaca-Mandic said she intends to study the timeliness of device adverse-event reporting as well.
In an editorial accompanying the study, the journal's editor, Dr. Rita Redberg, said, "Such reporting delays should never occur, as they mean that more patients are exposed to potentially avoidable serious harm, including death."
She proposed changes to the federal reporting system, including bypassing manufacturers and having more adverse-event reports sent directly to the FDA by caregivers.