January / February 2012
A Closer Look at FDA’s Adverse Event Reporting System
The U.S. Food and Drug Administration (FDA) is responsible for safeguarding patients and protecting public health by assuring the safety, efficacy, and security of medications. In order to accomplish this, the FDA’s primary monitoring process in preventing adverse drug events that occur with marketed drugs is the Adverse Event Reporting System (AERS), a computerized information database. The FDA defines an adverse event as any undesirable experience associated with the use of a medical product. Its focus is on serious adverse events, which are adverse events with a patient outcome of any of the following: death, life-threatening injury, hospitalization, disability or permanent damage, congenital anomaly or birth defect, and other serious outcomes.
The FDA uses the information collected in AERS to identify new drug safety concerns, which then may trigger a regulatory action to protect patients. When patients experience an adverse drug event, they can report the problem to their physician, the FDA, or the drug manufacturer. Healthcare providers have the option to voluntarily submit reports of adverse drug events to either the FDA or the manufacturer of the drug. Drug manufacturers, once informed of a qualifying adverse event by any reporter, are required to report the adverse events to the FDA.
More than 525,000 unique patient reports were submitted to AERS in 2010, with 9.6% of those adverse events resulting in patient deaths and nearly 21% resulting in patient hospitalization. Therefore, the FDA’s availability to monitor these reports quickly and accurately is fundamental to the FDA’s drug safety mission.
However, a number of insufficiencies appear when reviewing AERS. The fragmented and voluntary process of FDA adverse events reporting can be inaccurate and time-delayed. Drug safety professionals estimate that only 10% of adverse events are reported to the FDA every year, grossly underestimating the number of actual adverse events associated with a medication (Heinrich, 2000). Patients are exposed to the potential risk of adverse drug events until enough reports are submitted to the FDA. Given that AERS is updated just once per quarter, the public is typically alerted to new adverse events months after they occur. Such underreporting and delays make it extremely difficult for the FDA or any other interested party to effectively identify and publicize current adverse event risks. Furthermore, within the publicly available database, there is no standardization of drug names or other important clinical terminology, making searching and accessing information in regards to medications and their side effects nearly impossible. While the FDA has embarked on the Sentinel Initiative, a multi-year project to improve its drug safety oversight process, its ongoing reliance on AERS remains, as do the concerns about patient safety and timeliness of adverse drug events reporting.
What does this all mean? While the wheels of bureaucracy turn slowly and academics argue in journals about the utility of using AERS data to accurately calculate incidence rates, patients and healthcare providers are stuck in an information vacuum. There is no readily available, authoritative source of information on adverse event incidence and outcome rates. Simply put, there is no way to know how often a particular adverse event occurs and what happens to the patients who experience those adverse events. Currently, the available information on side effects is limited to a drug’s label. That information consists of a list of potential side effects and/or incidence rates of side effects from small, controlled clinical trials. As drugs are approved for sale and become widely used, the patient population increases exponentially, as does the potential for side effect problems.
What can be done to improve patient safety from this system? We propose three concurrent solutions: 1) make AERS data readily available and searchable through a website front-end, 2) increase physicians and other healthcare provider adverse event reporting, 3) include supplemental adverse event information disclosed in social media and online discussion forums.
At AdverseEvents, we have already addressed the first issue and are working on solutions for the other two. Our website at www.AdverseEvents.com includes all AERS data since January 1, 2004. Using RxFilter, our proprietary data refinement processes, we’ve standardized and normalized the AERS data and made it readily searchable by drug name, condition, and adverse event type. More than three million adverse event reports can now be queried and searched in every imaginable combination. Already this step alone is revealing important patient safety data that we expect will lead to further study and review in the academic community. For example, in a report published October 20, 2011, we examined 150,000 adverse event reports of serious muscle and tendon problems associated with statins. Contrary to previously held views, the study showed that there may be material safety differences within the class, with AstraZeneca’s Crestor having a significantly higher report rate that the other statins.
Credible reporting continues to limit the utility of AERS data. Since 2004, only 23% of AERS reports have come from physicians, 6% from pharmacists, and 16% from other health professionals. These rates have remained flat every year for the past 7 years. By contrast, the rate of consumer reporting has doubled from 22% in 2004 to 45% during the first two quarters of 2011. While the input from informed consumers is valuable, it is the trained, professional expertise contained in the reports from physicians, pharmacist, and other healthcare providers that is most vital, especially in proving a causal link between a particular drug and a particular adverse event (or group of adverse events).
Unfortunately, there is no requirement for reporting at the healthcare provider level, nor is there any incentive to promote reporting. The FDA’s current reporting process is clumsy and time consuming, limiting the practicality of reporting by busy healthcare professionals. Moreover, the FDA itself discounts the value of AERS data:
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. Therefore, AERS cannot be used to calculate the incidence of an adverse event in the U.S. population.
This creates a general belief by healthcare providers that submitting adverse event reports is essentially a waste of time, that the information goes into a black hole and serves no patient safety purpose. While we do not advocate a new burdensome requirement for adverse event reporting by healthcare professionals, we urge the FDA to make the reporting process frictionless, and we encourage more education and acknowledgment of the importance of AERS reporting among healthcare professionals. At AdverseEvents, we have simplified the reporting process by offering a single online form with simple drop-down fields. Upon reviews for accuracy, that data is then made immediately available online along with the AERS data, eliminating the black hole effect of the current system.
AdverseEvents makes a limited amount of data available for free on its website for all users. Full access to the data and the proprietary searching and alerting tools AdverseEvents has designed for the database are sold on a subscription basis to pharmaceutical, insurance, financial and other healthcare companies. The company will soon be launching a number of premium services for patients and healthcare providers to enable them to better understand and use the data.
Finally, we support efforts to utilize the immense trove of side effect and adverse events data currently residing in social media and other online destinations. While the rate of consumer reporting to the FDA has doubled over the past 7 years, the vast majority of consumers are not reporting their side effect problems to the FDA–they are discussing them online. The FDA has been slow to issue formal guidance for pharmaceutical companies on monitoring social media, but that should not negate the value of the information that resides there. While perhaps not as individually valuable as healthcare professional reporting, the sheer volume of consumer information being communicated online should be included in some way in the data used for monitoring drug safety. At AdverseEvents, we enable direct patient reporting of adverse events and are actively monitoring social media and other online outlets for information that can be used to supplement the AERS data and portray a more accurate view of drug safety.
No comprehensive discussion of patient safety is complete without addressing the void in accurate and reliable side effect information on prescription and over-the-counter medications. While the FDA’s AERS database is not a comprehensive solution, we believe that certain corrections to the data, improvements in reporter behavior, and utilizing consumer data available online will lead to a much more comprehensive understanding of patients’ side effect risks.
Brian Overstreet is founder and CEO of AdverseEvents, Inc. He is also chairman of the board of Sagient Research Systems, Inc., publisher of specialized research and data, a company he co-founded and served as president and CEO of the company for 10 years, More recently, Overstreet co-founded Bruliam Wines with his wife, Dr. Kerith Overstreet. A boutique California winery that has earned a number of 90+ point scores from Wine Enthusiast magazine, Bruliam Wines donates 100 percent of all profits to charity. Overstreet holds a bachelor’s degree in political science from the University of California at Berkeley. He may be contacted at