Incomplete AERs compromise drug safety monitoring

When a drug causes unexpected harm to patients, one way FDA learns of it is through adverse event reports submitted to the agency either by patients or indirectly through drug manufacturers. While manufacturers are required to report serious side effects or adverse events to the FDA, reporting by physicians and patients is voluntary.

But a recent study from the Institute for Safe Medication Practices (ISMP) revealed that the government’s reporting system is hampered by incomplete reports submitted by manufacturers. “It seems clear that this drug safety monitoring system is in need of modernization,” wrote Thomas J. Moore, QuarterWatch Project Director, ISMP, the lead study author, and his colleagues. “It suffers from a flood of low quality reports from drug manufacturers and has not yet been updated for the changing environment in which drugs are marketed to health professionals and consumers.”

See also: FDA moves to full-scale Sentinel program

Manufacturers report lack of data

The study examined more than 847,000 case reports received in the year prior to March 2014. The reports of adverse drug events (AERs) are supposed to include a patient’s age, sex, and the date of the incident. While 85% of the reports submitted by patients directly to the FDA were considered “reasonably” complete, fewer than half the reports sent by manufacturers could be similarly characterized. Reports from drug manufacturers make up 97% of all AERs.

“While drug manufacturers are now reporting adverse drug events in unprecedented numbers from around the world, we judged that the overall completeness of adverse event report[s] was poor,” Moore and his co-authors wrote. “The weakest performance was seen in four companies that submitted reasonably complete reports in only 15% or fewer cases; not one manufacturer equaled the FDA 85% record for complete reports; and only [7% of] manufacturers reported at least age and gender in 90% or more serious reports.”

Complete vs. incomplete reporting

The study noted manufacturers who submitted the “most reasonably complete” reports. They were Ariad (77.7%), GE Healthcare (77.1%), Vertex (73.7%), United Therapeutics (73.1%), and Biogen (72%).  According to the study, the weakest performers were Par (0.9%), Cubist (8.1%), Roxane (10.2%), Millennium (15.3%), and Westward (16.2%).

“We can’t think of a good reason why the quality and completeness of serious adverse event reports collected by drug manufacturers is so much worse than for those collected online at the FDA,” wrote Moore and his co-authors. “And does the system really need thousands of non-serious reports of the sniffles or that an injection was painful? Providing FDA feedback to companies submitting large numbers of reports with missing data is elementary quality assurance in the digital data era.”

The study recommends several changes to the adverse event reporting process, including the inclusion of new data elements, specific lists of questions for manufacturers to ask, and improvement of patient death reports.

“There is no point in manufacturers submitting thousands of reports of deaths in which a possible drug role was never alleged, ascertained, or investigated,” Moore and his co-authors wrote. “In all of these situations, much could be gained from requiring a simple critical question in company-initiated contacts that asked: ‘Was this drug suspected of contributing to the event?’”

The study concluded that, despite its flaws, FDA’s adverse reporting system is an “invaluable asset” and that its improvement should be a high priority.

See also: ISMP calls for FDA action on dabigatran bleeding risk