Science and Law
17th January 2013

Adverse Drug Reactions in Pharmaceutical Litigation

Pharmaceutical litigation is characterized by complex scientific studies of various types, including randomized controlled clinical trials and analytical epidemiological studies of varying levels of rigor (usually cohort or case control study designs).

Adverse Drug Reactions in Pharmaceutical Litigation

Pharmaceutical litigation is characterized by complex scientific studies of various types, including randomized controlled clinical trials and analytical epidemiological studies of varying levels of rigor (usually cohort or case control study designs). These studies evaluate relationships between a drug exposure and adverse event outcomes as a function of a number of conditions. A rigorous assessment of these studies is critical to the success of the case.

However, there is another type of evaluation or assessment that often gets overlooked: a systematic evaluation of adverse drug reactions (ADRs). These medical events are collected in a database maintained by the Food and Drug Administration (FDA) called the adverse event response system, also known as AERS (there is also a special reporting system specifically designed for medical events linked to vaccine exposure, known as VAERS). Medical events are reported to AERS by health care professionals as well as directly by patients.

On September 10, 2012, AERS was converted over to a related, but more advanced database called FAERS (FDA Adverse Event Database). However, most of the fundamental principles of AERS have been maintained.

The data contained in AERS has a number of limitations, including the following:

FAERS is a Spontaneous Reporting System

FAERS is known as a voluntary, “spontaneous reporting system,” which means that the medical events come in to the system spontaneously as opposed to through a systematic, protocol-driven process. This means that medical events reported through AERS or FAERS could be driven by many factors other than a causal relationship between the drug and the event. For example, physicians may report an event linked to a drug based on unsubstantiated media scrutiny allegedly linking the drug to the medical event. In this case, there may be no causal association between the drug and the event and yet there may be many drug-event combinations in the FAERS or AERS database.

No Independent Verification

Because there is no independent verification that the event actually occurred or that the patient even took the drug, the integrity of the data in FAERS or AERS is questionable. Because anyone can submit information to FAERS, it is even possible that plaintiff lawyers could be submitting information to FAERS that could artificially inflate or distort the case count.

At the end of the day, FAERS and AERS are elaborate case series linking drugs to a medical events. The information contained in the database can lead to hypotheses that must be tested using more controlled, protocol-driven methodologies using either randomized trials or controlled observational methodologies.

FDA enumerates the limitations of the FAERS database on its website:

“First, there is no certainty that the reported event (adverse event or medication error) 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 reports for every adverse event or medication error that occurs 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. Therefore, FAERS data cannot be used to calculate the incidence of an adverse event or medication error in the U.S. population.”

PRR Analysis

Despite the limitations of the AERS database, it is critical to be aware of the data contained in FAERS and AERS with a drug that is the subject of a personal injury lawsuit. For example, plaintiff experts may perform a crude analysis of AERS looking at the proportion of events attributed to the drug as a function of the proportion of events attributed to the entire AERS database or to a comparator drug. If the proportion of events for the drug is higher than the proportion of events for some comparator, the case can be made that there is some sort of relationship between the drug and the event. This analysis (known as a Proportional Risk Ratio or PRR) can be used by plaintiffs to make the assertion that there is a causal relationship between the drug and the event.

Quarterly Data Files

Since 2008, FDA has been performing quarterly assessments listing potential signals of serious risk. These signals have been identified by FDA as potential safety concerns, but inclusion on this list does not mean that FDA has causally linked the drug to the event. As FDA specifies on their site:

“The appearance of a drug on this list does not mean that FDA has concluded that the drug has this listed risk. It means that FDA has identified a potential safety issue, but does not mean that FDA has identified a causal relationship between the drug and the listed risk. If after further evaluation the FDA determines that the drug is associated with the risk, it may take a variety of actions including requiring changes to the labeling of the drug, requiring development of a Risk Evaluation and Mitigation Strategy (REMS), or gathering additional data to better characterize the risk.”

Nevertheless, because of the innuendo associated with this listing, it is extremely imporant for a defense lawyer to be aware of this list when trying pharmaceutical cases. The most recently compiled quarterly report of drug-event combinations can be found here for the period April – June 2012.

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