Sentinel: Harnessing the Power of Databases to Evaluate Medical Products

By: Michael D. Nguyen, MD

Clinical trials are designed to evaluate the safety and effectiveness of medications. But the number of participants in clinical trials represents only a fraction of the number of people who will ultimately use the product after FDA approves it. Occasionally, rare and unexpected health problems (which we call “adverse events”) become apparent only after a medical product is on the market and many more people use it. That’s why it’s so important for FDA to continue to monitor the safety of medical products, a practice called surveillance.

Michael NguyenMost safety surveillance systems are passive: They rely on health care professionals and consumers to notice and report adverse events. Although these passive systems remain essential, they have certain limitations. For example, health care professionals and consumers might not recognize that the product is the cause of an adverse effect and not report it to FDA. Or, they might report a suspected adverse event that’s not truly the cause of a problem the consumer experiences.

Now imagine if we could actively search more than 100 million health insurance records to uncover possible adverse events, rather than relying on doctors and patients to report them. Such a system would enable us to get continuous feedback on the use of medicines under real-world conditions – feedback that might help us to discover unexpected patient reactions or unexpected drug interactions.

FDA scientists have partnered with the Harvard Pilgrim Healthcare Institute to create such a surveillance system, called Sentinel. Within Sentinel, FDA has supported the development of software that analyzes information from health insurance and health record databases to search for evidence that certain products are linked to specific adverse effects. Although these data are protected behind tight firewalls and remain under the control of the original health insurance plans that created them, the software makes it possible to analyze the information without disclosing identifying information in order to strictly maintain patient privacy.

FDA and Harvard Pilgrim Healthcare Institute are using this surveillance system to determine whether a certain type of immune therapy is associated with heart attacks or strokes, and to better define the true rate of acute lung injury after transfusions of certain blood components.

More recently, FDA completed its first study using the Sentinel system, which evaluated the safety of the two current vaccines (RotaTeq and Rotarix) that prevent rotavirus infection (the leading cause of severe diarrhea and dehydration in infants). The new study revealed that these rotavirus vaccines slightly raise the risk of a rare bowel problem (intussusception) that previously caused a prior rotavirus vaccine (Rotashield ) to be voluntarily withdrawn from the market by its manufacturer. But the Sentinel study showed that the newer vaccines have a much lower rate of this bowel problem and are safer, with the benefits outweighing the risks, including the risk of intussusception, associated with vaccination.

The Sentinel rotavirus vaccine and immune therapy studies are examples of how FDA scientists are harnessing the power of big electronic databases to ensure the safety of the medical products we use every day.

Michael D. Nguyen, MD, is the Acting Director of the Division of Epidemiology in FDA’s Center for Biologics Evaluation and Research

FDA’s Mini-Sentinel exceeds 100 million lives (and counting)… A major milestone in developing a nationwide rapid-response electronic medical product safety surveillance program

By: CDR Melissa Robb

Having secure access to the electronic healthcare data of patients is an essential 21st Century tool for detecting potential safety problems with medical products once they are in common use.

This is because studies conducted prior to approval may not be able to detect rare problems or problems that might emerge following long-term use of a product.

Congress recognized this need for additional information in the FDA Amendments Act (FDAAA) of 2007 when it authorized FDA to develop a nationwide rapid-response electronic surveillance system for monitoring the safety of FDA-regulated medical products such as drugs, vaccines, other biologics, and medical devices.  FDA calls this the Sentinel System.

Now FDA is proud to report that it has met and EXCEEDED the legislation’s goal of achieving secure access to data from 100 million patients by July 1, 2012. In fact, FDA met that goal in December, 2011, and currently has secure access to data concerning approximately 126 million patients nationwide derived from 17 different data partners.

To better understand how the Sentinel System will work, FDA has been conducting a pilot program, dubbed “Mini-Sentinel,” that incorporates access to these 100 million-plus records. So far FDA has used Mini-Sentinel to conduct more than 120 data requests to gather safety information on various medical products.

As an example of the promise of this system, consider FDA’s recent use of the Mini-Sentinel pilot to help inform our ongoing safety analysis of the blood pressure drug olmesartan. FDA had received reports through our Adverse Event Reporting System (AERS) suggesting that olmesartan was associated with more cases of celiac disease than other “sartan” drugs in its class (losartan, irbesartan, telmisartan, valsartan). Celiac disease is a potentially dangerous condition in which the small intestine is damaged and the patient cannot absorb nutrients. FDA, through Mini-Sentinel, submitted a query request to the data partners for specific information on the number of patients with celiac disease who had taken these drugs.  The resulting data report allowed FDA to determine that celiac disease did not occur significantly more often with patients who had taken olmesartan than with those who had taken other “sartan” drugs.

While the Sentinel System holds much promise, it is intended to supplement, not replace, FDA’s existing safety surveillance tools, including AERS, which relies on individual reports filed by manufacturers, health care providers and patients. When weighing risk against benefit of a medical product, FDA compiles information from a variety of sources before making a regulatory decision.

FDA is committed to maintaining the highest world-wide standards of safety surveillance capabilities. The Sentinel System  is our next step forward towards that goal.  Stay tuned. As always, we’ll keep you informed on progress.

CDR Melissa Robb is FDA’s Associate Director for Regulatory Affairs, Office of Medical Policy Initiatives