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Regulatory Focus™ > News Articles > 2019 > 5 > FDA Officials Explain When Litigation Can Impact Drug Safety Signals

FDA Officials Explain When Litigation Can Impact Drug Safety Signals

Posted 20 May 2019 | By Zachary Brennan 

FDA Officials Explain When Litigation Can Impact Drug Safety Signals

The submission of litigation-associated adverse event reports (LARs) to the US Food and Drug Administration’s (FDA) Adverse Event Reporting System (FAERS) can have an impact on detecting safety signals, Monica Muñoz and Gerald del Pan of FDA’s Office of Surveillance and Epidemiology wrote recently in a research letter to the journal Drug Safety.

The letter came in response to a study in the same journal that found lawyer-submitted reports in FAERS did not meaningfully distort known safety signals for two specific drugs subject to high-profile litigation for other adverse events (AEs).

Del Pan and Muñoz used an algorithm to identify LARs received in FAERs through the end of 2018, finding that peaks in LARs “can be attributable to highly publicized drug safety regulatory actions.”

Of the 209,198 signals of disproportionate reporting (SDRs) identified from two FAERS datasets (one with and one without LARs), the authors found 90% of SDRs overlap. But about 4% of SDRs only became apparent when LARs were excluded.

“The most frequent unmasked SDR events included chronic kidney disease (n = 74), renal failure (n = 59), and acute kidney injury (n = 57). In contrast, the most frequent SDRs that only appear in the dataset that includes LARs were injury (n = 126), cerebrovascular accident (n = 112), and pain (n = 98),” they explained.

They also looked at the example of the gut motility stimulator metoclopramide, of which they found 65% of the 27,918 metoclopramide reports received through 2018 were classified as LARs.

“Drugs with a high proportion of LARs, particularly when concentrated on events not frequently reported to the FAERS, can create an environment resulting in significant masking of SDRs, both within the AE profile of the litigated product and with the AE(s) that are the subject of the litigation for other products. The LARs in the FAERS are predominantly from the US; however, these reports may also be found in other global spontaneous reporting databases, depending on the reporting requirements of individual countries,” Del Pan and Muñoz wrote.

“It is imperative for safety scientists using SDRs as a screening tool to be conscious of stimulated reporting sources. We expect to continue to receive reports disproportionately focused on particular drugs and AEs secondary to litigation. Similarly, other influences such as advocacy groups and industry-sponsored programs can also have significant impacts on timely signal identification and evaluation,” they added.

Further research is also necessary, they said, to better deal with the bias introduced by stimulated reporting on signal identification.

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