Drug makers must report side effects to regulators, but the amount of useful information can vary depending upon which regulator gets the data, according to a new analysis.
A team of researchers examined a dozen brand-name drugs used to treat depression and seizures and found that, on average, the manufacturers filed 77 more side effects reports with the US Food and Drug Administration than with the European Medicines Agency.
On average, 71 percent of the side-effect terms listed in the reports submitted to the FDA were not filed with the EMA, or vice versa. And in 86 percent of reports submitted to the FDA, there was more information on the source of the report — such as a spontaneous patient report during treatment or if it occurred during a trial — than what was provided to the EMA.
The upshot: On average, only 29 percent of the side effects were reported to both agencies. Moreover, most of the reports lacked information on duration and seriousness of the side effects, as well as the extent to which the reactions were reversible.
The researchers, whose analysis appeared earlier this month in BMJ Open, argued that the inconsistent approach drug makers take to filing side effect reports about the same drugs to different regulators does a disservice to patients.
Side effect information for a drug “should not vary depending on the location of prescribers and patients,” wrote Dr. Victoria Cornelius, one of the researchers, who is deputy head of statistics at the Imperial College of London School of Public Health, in a note to us. “Without this information, prescribers cannot appropriately inform patients on the totality of the risks of taking a medicine.”
Like any study, there are limitations. In this instance, the researchers note that findings may vary depending upon the therapeutic area and the year in which the drugs were approved. Another factor is that coding differences used by drug makers might have accounted for some discrepancies. Also, this was a rather small sample of medicines.
One safety expert noted a possible explanation for some differences may be due to regulatory practice for reporting adverse events in clinical trials. The FDA demands a table of more frequently reported side effects with a column for a drug and a comparative medicine, said Thomas Moore, a senior scientist with the Institute for Safe Medicine Practices, a nonprofit that tracks drug safety issues. There is no information about causality and readers are left to make inferences.
In any event, the researchers write that side effect reports by the same drug maker should be similar in the US and Europe, with any differences due to regulatory recommendations. From their analysis, the researchers argue that drug makers are filing an adverse event that is actually not related to a drug, which can make it difficult to know whether the medicine somehow created an issue for patients.
“It becomes that you can’t see the wood for the trees,” Cornelius wrote us.
She also noted that, since the increased regulation in clinical trials in the early 1990s, the ability to collect “good quality adverse event data” has improved. But the approaches taken to identifying side effects reported in clinical trials, and then summarizing this information, are “lagging behind.”
Moore agreed that reporting needs to be improved.
“This study shows that the reporting of drug adverse effects on product information is fragmentary and inconsistent,” said Moore. “In this sample, neither the FDA nor the EMA versions provided much information about the onset, duration, and severity of drug side effects. Instead they provided just lists that were not necessarily in agreement.”