FDA’s Adverse Event Reporting System (AERS) is a database that allows physicians, patients, and others to call attention to post-marketing drug safety issues. Reporting in AERS is voluntary, and thus data far from reliable. Still, the statistics are used by FDA as a means of determining potential safety concerns of drugs on the market.
Increasingly, those who submit AE reports are lawyers—one would assume class-action lawyers and others with a stake in the results. For most drugs, lawyer submissions do not represent a significant portion of the reports. For others, however, they do, and this “lawyer over-reporting” could be significantly skewing results, causing “signal inflation” and potentially creating false signals about safety concerns, say Nicholas Schluterman and Sheila Weiss Smith of the University of Maryland, Baltimore.
Schluterman and Smith have been researching lawyer reporting in AERS, and Schluterman presented their findings at the DIA 2011 conference in Chicago this week. View the poster PDF here.
Schluterman explains that lawyer input may be biasing the Proportional Reporting Ratio (PRR) derived from AERS data. “The number 2 is an important cutoff for signal inflation,” he says. “A PRR of 2 is a commonly-accepted threshold dividing weak from strong associations; a ‘signal’ occurs when the PRR is over 2. If lawyer bias has caused a signal inflation of over 2.0, then that means that there is so much bias that it could have created a signal when there was no true association to begin with.”
PRR is a measure of a drug-reaction association, Schluterman notes, so the signal inflation also refers to the drug with a specific reaction. For Celecoxib (Celebrex) with cardiac disorders, for instance, lawyer reporting may have created a signal inflation of 2.86, the researchers found. For Alosetron (Lotronex) with GI atonic and hypomotility disorders, it was 2.19.
According to the AERS information page on FDA’s website, the data should be taken with a grain of salt: “AERS data do have limitations. First, there is no certainty that the reported event was actually due to the product. FDA does not require that a causal relationship between a product and event be proven, and reports do not always contain enough detail to properly evaluate an event. Further, FDA does not receive all adverse event reports that occur with a product. Many factors can influence whether or not an event will be reported, such as the time a product has been marketed and publicity about an event.”
Schluterman and Smith note that “lawyer-originated reports represent a small but persistent proportion of all AERS reports,” and that “a large proportion of lawyer reports are for a small number of drugs.” This should be cause for concern.