Drug Industry’s Unacceptable Delays in Reporting Adverse Events To the FDA

A study published in the September issue of JAMA Internal Medicine revealed that pharmaceutical companies too often fail to promptly report to the Food and Drug Administration (FDA) unexpected serious adverse events associated with use of their products. Delays in reporting such events undermine a key component of our nation’s system for monitoring the safety of prescription drugs.

Before a new drug is approved by the FDA, it undergoes testing in clinical trials. But these trials typically involve relatively few patients; last only months, if not weeks; and enroll patients healthier than those seen in the average clinical practice. Because of these limitations, serious but uncommon adverse events caused by prescription drugs routinely are not detected until after the drugs have been on the market for years and used by hundreds of thousands or millions of patients. Uncovering these adverse events quickly and reliably requires a robust, well-functioning postmarketing surveillance system.

Thus, to protect patients, FDA regulations for decades have required that manufacturers report to the agency any unexpected serious adverse events associated with use of their drug products within 15 days of initial receipt of the information from health care providers or other sources.[1] Serious adverse events include those resulting in death, life-threatening effects, hospitalization, disability or birth defects.

In the recent JAMA Internal Medicine study, researchers analyzed over 1.6 million reports of unexpected serious adverse events submitted to the FDA from 2004 to 2014.[2] They found that 10 percent of these reports, including approximately 40,000 that involved a patient death, were not reported to the FDA within the required 15-day window. Nearly 25 percent of the delinquent reports were submitted more than 180 days after the companies initially received the information. Strikingly, reports of fatal adverse events were more likely to be delayed than reports of nonfatal events.

As Rita Redberg, editor-in-chief of JAMA Internal Medicine, observed in a note about the study, "Such reporting delays should never occur, as they mean more patients are exposed to potentially avoidable serious harm, including death."[3]

The FDA has the authority to withdraw approval of a drug and prohibit its marketing if the manufacturer fails to report adverse events as required by regulations.[4] Given the evidence of widespread illegal delays in reporting adverse events, the agency should start invoking that authority. Making an example of even a couple of the worst offending companies would send seismic signals throughout the entire pharmaceutical industry and prompt all manufacturers to become more compliant. So what is the FDA waiting for?

References

[1] 21 C.F.R. § 314.80.

[2] Ma P, Marinovic I, Karaca-Mandic P. Drug manufacturers’ delayed disclosure of serious and unexpected adverse events to the US Food and Drug Administration. JAMA Intern Med. 2015;175(9):1565-1566.

[3] Redberg RF. Improving manufacturer reporting of adverse events to the US Food and Drug Administration (editor’s note). JAMA Intern Med. 2015;175(9):1566-1567.

[4] 21 C.F.R. § 314.80(k).