From a Clinical Perspective
Drug safety -- past, present and the future
A conversation with Dr. Gerald Dal Pan, director, Office of Surveillance and Epidemiology in FDA’s Center for Drug Evaluation and Research
FDA's Adverse Event Reporting System (FAERS)
Tell me a little bit about FAERS. It recently replaced the old AERS system – what are the advantages of the new system?
Dal Pan: FAERS is FDA's Adverse Event Reporting System and as you said, it recently replaced the Adverse Event Reporting System. FAERS is a system in which we enter, manage, analyze and review adverse event reports that we receive from either regulated industry or from the public. Regulated industry is required to submit reports. The public can also submit reports to us voluntarily.
About 95 percent of the reports come from regulated industry -- although the companies receive those reports from the point of care, such as physicians, nurses, pharmacists, patients and caregivers. The other five percent of the reports come directly to FDA through our MedWatch program.
We entered a little more than 900,000 adverse event reports in 2012. The entire database has more than 6 million reports. It's important that our safety evaluators and other drug safety staff have a database system they can query efficiently. They can use FAERS to find cases, and use different informatics tools and statistical techniques to identify safety signals.
(NOTE: an adverse event can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medical product, whether or not it is related to the medical product.)
Under FAERs have you seen an increase in the number and quality of reports?
Dal Pan: FAERS is an informatics system that allows us to manage and analyze the reports efficiently. It doesn't change the nature of the reports we get. Nor does it increase or decrease the number we get. For the last 10 years, the number of reports has been increasing every year. It's doubled in the last four or five years, making it more important to have good, efficient informatic systems. Finding drug safety signals is a lot like finding a needle in a haystack. FAERS is a good tool to sift through that haystack efficiently.
Signal detection and data mining are important aspects of drug safety -- briefly describe each
Dal Pan: Signal detection is finding that needle in the haystack. We have these 6 million reports. In those data, there is information that tells us something new about an adverse event. Sifting through that information and finding what it’s telling us about the adverse event is signal detection. Data mining is the use of computerized methods to look at the data in an organized way; to find patterns that a human being couldn't find, especially if they have to go through 6 million reports.
The Sentinel Initiative
CDER Director Janet Woodcock recently talked about the Sentinel network. She said it now covers millions of people. What is this network and what type of results are you seeing from the data?
Dal Pan: The Sentinel Initiative is a broad initiative that FDA launched in 2008. It is comprised of two parts: the Mini-Sentinel Initiative and the federal partner collaborations. The Mini Sentinel Initiative involves the participation of many different data partners. Each data partner has electronic health care information about the medicines people take and their medical diagnoses; the entire system covers more than 130 million people.
When FDA has a query, the query goes to an operations center which writes a statistical program to answer the query. That program is sent to all the data partners. Each of them runs it on their own data, behind their own firewall to protect personal privacy, and sends summary data back to the operations center. For the system to run efficiently, all the data partners structure their data in the same way, which goes by the name “common data model.” The operations center collects these summary data from the data partners, aggregates them and sends a final report back to FDA.
The Mini-Sentinel was launched a few years ago and has become part of our safety evaluation process; it’s one more item in our toolkit. It doesn't replace anything else we have; it’s one more way of looking at safety data.
The second part of the Sentinel Initiative involves collaborations with our federal partners. These include the Center for Medicare and Medicaid Services, the Veterans Administration and the Department of Defense. Each of them either administers or runs a health care system and each has data that link medicines people take to their medical diagnoses. Our epidemiologists and other safety staff here work with epidemiologists and safety staff at these agencies across the government and we can perform drug safety analyses. Again, we only see aggregated data, so personal privacy is maintained.
So before the Sentinel Initiative, what type of system was used?
Dal Pan: We've been using electronic health care data for about 20 years. But 20 years ago, there wasn't as much of it available as there is today, and the computing power to crunch all the numbers wasn't there. Each of the Sentinel intiatives integrates multiple sources of data into a single, large networks; the capacity for such a large network wasn’t there years ago. Previously we relied heavily on the spontaneous reports that we had in FAERS and AERS before it. However, while Sentinel and our federal partners are very important and provide useful data, they don't replace the good, spontaneous reports that we have in FAERS. Rather, they complement FAERS data.
Drug Safety Communications
Let's talk about drug safety communications. DSCs seem to be a proactive way to send the latest information to the public – are you pleased with this effort; how can it be improved?
Dal Pan: Our drug safety communication program has really grown a lot in the last five years. In my opinion, it has really been one of the best things we've done at FDA. The public wants to know about drug safety information; they want to know things early; they want good, useful data, and they want the facts to enable them to make informed decisions. We and our colleagues in the Office of Communications have worked to improve this program over the last few years. The type of safety communication we have has evolved as we have refined our thinking on communication. We now have a high quality, single document that's useful for multiple stakeholders. And it’s a very integral part of our transparency efforts.
There have been discussions about the impact of social media in drug safety. If a drug manufacturer tracks chatter about a possible adverse event with its product, is the company obligated to report this information to FDA?
Dal Pan: There is a lot of interest regarding social media and its potential use in drug safety surveillance and detecting adverse events. While CDER does not have specific guidance for industry about social media and adverse event reporting, there is guidance about adverse event reporting in general and information received from the Internet. The principals of adverse event reporting apply regardless of the forum in which industry learns about it. We recognize that there are certain aspects of social media that are different from telephone calls, letters and traditional emails. We are working to see exactly how those differences may require more refined guidance on our part.
Risk Evaluation and Mitigation Strategy (REMS)
How's the REMS effort going?
Dal Pan: That effort is going well. REMS has consumed plenty of our time since the amendments act (Food and Drug Administration Amendments Act) was passed in 2007. That work has crossed multiple offices and divisions in CDER and FDA. We have a lot of information out there about REMS and our thinking has evolved over the years. We are going to work on guidance for industry that sets forth our current thinking about when a REMS is required and other aspects of the program. Because we have the REMS provision, it allows us to make some prescription drug products available to the public that otherwise wouldn't be available.
Changes in drug safety
What are the most important changes you would like to see in drug safety in the next 5 years – changes that CDER can make?
Dal Pan: I think one would be a better understanding of the pharmacologic and biologic basis of adverse events -- especially those that are not related to the pharmacology that underlies a product's therapeutic effects. I would like to see better integration of risk management into the health care system – though such an effort would go well beyond FDA’s purview. I think that would benefit patients and practitioners. I would like expanded sources of data, especially related to how medicines are used in ways that may not promote the safest possible use of those medicines. Finally, I would like more education on medication safety for patients and practitioners. For practitioners, I’d like to see this start early in their training.
Gerald J. Dal Pan became director of the Office of Surveillance and Epidemiology (known then as the Office of Drug Safety) in November 2005. Before that, he was the director of the Division of Surveillance, Research, and Communication Support in CDER's Office of Drug Safety, a position he held since December 2003.
He received his medical degree from Columbia University, and his Master's degree in clinical epidemiology from Johns Hopkins University. He trained in internal medicine at the Hospital of the University of Pennsylvania, and in neurology at Johns Hopkins Hospital.