Another important step in FDA’s journey towards enhanced safety through full-scale “active surveillance”

By: Janet Woodcock, M.D.

They say the longest journey begins with a single step. In 2008, FDA launched the Sentinel Initiative and thus began a long journey toward the challenging goal of developing a full-scale medical product safety monitoring program using an important scientific technique called “active surveillance,” which complements our FDA Adverse Event Reporting System (FAERS). FAERS is already well developed and uses the equally important technique of “passive surveillance.” Today, I’d like to recognize our progress along the way.

Janet WoodcockAfter a successful five-year pilot program, which began in 2009, FDA’s Mini-Sentinel program is now transitioning, as planned, to the full-scale Sentinel System. I’d like to share with you the success of our Mini-Sentinel pilot program and some of FDA’s visions for our new leg of the journey toward full-scale “active surveillance” under the new Sentinel System.

First, a quick discussion of the importance of “active surveillance”: Over many years, FDA’s program that we now call FAERS has been our main tool for assessing the safety of medical products. This system relies on patients, medical professionals, and product manufacturers to report to us potential safety issues of the products FDA regulates.

FAERS is an invaluable asset, and we’re not seeking to replace it. However, the Sentinel System offers us the exciting possibility of not waiting for safety information to come to us in the form of reports, but rather it enables us to go out and get that information, adding greatly to our safety monitoring capability. This is active surveillance.

Over the past five years, the Mini-Sentinel pilot program has established secure access to the electronic healthcare data of more than 178 million patients across the country, enabling researchers to evaluate a great deal of valuable safety information. While protecting the identity of individual patients we can get valuable information from Mini-Sentinel that helps us better understand potential safety issues, and share with you information on how to use medicines safely. We have used Mini-Sentinel to explore many safety issues, helping FDA enhance our safety surveillance capabilities, and giving us valuable input in decision-making on drugs and vaccines.

We’re now well on our way to developing a nationwide rapid-response electronic active surveillance system, Sentinel System, for monitoring the safety of FDA-regulated drugs and other medical products.

So where does our journey take us from here?

  • FDA will build on the successes of the Mini-Sentinel Pilot. We have a variety of safety assessments ongoing under Mini-Sentinel that will continue and we will seek to expand our reach and capabilities with the Sentinel System;
  • Mini-Sentinel gave us an important start, but it is essential to continue to develop and refine existing scientific methods to evaluate the data we access through the Sentinel System;
  • We see Sentinel as a potentially valuable national resource for other safety researchers, besides those at FDA. Looking even further ahead, our hope is that, working with other scientific groups, we will be able to create a National Data Infrastructure that would enable other users (e.g., other governmental agencies, researchers from academia or industry) to access the Sentinel infrastructure for multiple purposes (e.g., medical product research, quality improvement);
  • Not only will such access directly serve the public health, it will also help sustain these programs because stakeholders will have an incentive to provide support (financial and otherwise) for its maintenance and growth.

From the outset, the goals of the Sentinel Initiative have been large and of ground-breaking scale. We knew it would be years in the making, but Mini-Sentinel’s successful completion marks important progress. We look forward to continuing and expanding our active surveillance capabilities as we now transition to the full-scale Sentinel program.

Janet Woodcock, M.D., is the Director of FDA’s Center for Drug Evaluation and Research

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