Postmarket Drug Safety: The View From the FDA

Laurie E. Scudder, DNP, NP


May 19, 2017

Editorial Collaboration

Medscape &

Maintaining Vigilance in the Postmarket Period

Medscape: The FDA's Sentinel Initiative is a national electronic monitoring system used to identify postmarket risk. Can you describe this initiative? What are the benefits and limitations of Sentinel? What is the role of prescribers in this system?

Dr Dal Pan: Sentinel is one of our bigger drug safety initiatives and was begun in 2007 following the passage of the FDAAA, which required us to put together a system with data on 25 million lives by 2010 and 100 million lives by 2012. We met and exceeded those goals. During the initial work between 2009 and 2014, we launched the mini-Sentinel pilot through a contract with the Harvard Pilgrim Health Care Research Institute in Boston. They then subcontracted with multiple other data partners. These organizations are mainly large health insurers that have significant amounts of electronic healthcare data on defined populations. These data include medical diagnoses and information on dispensed prescriptions, including when a medication was started, and things that might have happened with that patient afterward.

This effort required that the partners develop a common data model for all necessary information so that it is all essentially written in the same language. When a drug safety question arises, we determine whether Sentinel might be an appropriate tool to answer the question. We then form a team with the operating center in Boston, discuss the question, and specify exactly what the query will look like. This way, we have a common understanding of the question and we know what data are needed to provide an answer. The operating center writes a statistical, analytical program using the language of this common data model to share with these data partners. The data partners run the data behind their own firewalls. It's an important part of the system that each data partner retain control of its data and that individual patient-level data do not go outside of the data partner's firewall.

The data partners then generate summary statistics which are returned to the Sentinel operating center in Boston. The Sentinel operating system aggregates those data and shares them with FDA for interpretation and analysis.

The Sentinel system does have some limitations. Like all data based on prescriptions claims, it doesn't include over-the-counter (OTC) medicines because they are not included in prescription databases. It doesn't have a linkage to mortality records, although we're working on adding that capability. Because it deals with primarily a privately insured population, it has underrepresentation of people over 65. To get around that, we're working to integrate the Centers for Medicare & Medicaid Services into that so that the system will include Medicare data.

One feature of postmarket safety is having systems to detect the unexpected. MedWatch is the system that allows us to do that.

Medscape: Sentinel, then, is a passive system in that it's collecting data that already exist and doesn't require active reporting on the part of the public. It sounds like the MedWatch and Sentinel initiatives complement each other, but Sentinel does not supplant the MedWatch system—correct?

Dr Dal Pan: That's exactly right. We've always said that Sentinel is another tool in the toolbox. One feature of postmarket safety is having systems to detect the unexpected. MedWatch is the system that allows us to do that. Right now, our use of Sentinel is limited to evaluation of signals of safety. It does not generate signals. These are complementary approaches and we don't expect Sentinel—or anything else, for that matter—to supplant the MedWatch program. Slightly over half of the safety reports that we generate are the result of adverse event reports.