Details of adverse drug reactions (ADRs) included in official product information differ significantly between the United States and Europe, according to research.
The study focused on branded anticonvulsants and antidepressants and showed that on average only 29% of ADRs were reported in both territories’ documents, while the number of reported ADRs was consistently higher in the United States.
“The information about side effects contained in these drug documents is inconsistently presented and the volume of ADRs included is often overwhelming,” says lead author Victoria Cornelius from King’s College London. “As a result it’s hard to see how this can be useful for prescribers and patients.”
The team compared the EU summary of product characteristics (SmPC) and its US equivalent — the US product insert (USPI) — for 12 drugs, or 24 paired documents, marketed in both regions. Among the drugs included were gabapentin, lamotrigine, pregabalin and fluoxetine.
Reporting their findings in BMJ Open
(online, 20 March 2016), the researchers found that the median number of ADRs reported in the USPI was 201 compared with 114 in the SmPC. But, for the most part, the documents did not include relevant information such as the duration, onset or reversibility of ADRs. They also found that US documents were more likely to report the source of the ADR; 10/12 USPIs reported the source of at least 80% of ADRs compared with 5/12 SmPCs.
But the researchers note that the data in US documents were not necessarily more useful and may be harder to absorb than the data contained in EU documents. It was also unclear whether the ADRs included in US documents were truly ADRs rather than adverse events (AEs), which can be unrelated to the drug itself.
Cornelius suggests the disparity between EU and US documents could be due to manufacturers being overcautious about reporting ADRs in the United States due to fear of litigation.
Stephen Evans, a pharmacoepidemiologist at the London School of Hygiene and Tropical Medicine, who was not involved in the study, says there have been efforts in the EU to try to distinguish ADRs from AEs. In the United States, it is often in the manufacturers’ interests to add ADRs to the label, he adds.
“While superficially US and EU guidelines may look similar, there does seem to be a lower threshold for inclusion of AEs in the US label,” he says. “It is not necessarily helpful for patients or health professionals to have a very long list of possible ADRs.”
The researchers say that better approaches to identify, select and summarise harm data are needed to inform prescribers and patients about drug safety.
“For example, we could use more power approaches underpinned by statistical methodology to flag signals for potential ADRs in clinical trials, rather than relying on rule-based methods such as ‘adverse events in the active arm that are twice the placebo rate’,” suggests Cornelius.
“ADR information should not vary depending on the location of prescribers and patients — regulators should encourage international consistency,” she adds.
The European Commission is currently conducting a review of the information provided to patients and prescribers and plans to report to the European Parliament on the “current shortcomings in the summary of product characteristics and the package leaflet”.
 Cornelius VR, Liu K, Peacock J et al. Variation in adverse drug reactions listed in product information for antidepressants and anticonvulsants, between the USA and Europe: a comparison review of paired regulatory documents. BMJ Open 2016;6:e010599. doi: 10.1136/bmjopen-2015-010599