A progress review of FDA’s ‘Sentinel Initiative’ was published online on JAMA’s website this Wednesday which stated that the huge data monitoring program is still in its maturation phase. The pilot phase, called the ‘Mini Sentinel’, was first published back in 2008, and has since then become a powerful collection, but it has still not reached its full potential in terms of accomplishments. The FDA’s Sentinel Program claims to be comprised of about 200 million patients and 5.5 billion patient encounters data from all over the US.
The original aim of the Sentinel was to act as an active drug safety monitoring system which provided access to data for analysis while protecting the patient privacy. The Sentinel is a creation of a public-private partnership with 18 data partners, majorly health insurers like Humana, Aetna, Kaiser Permanente, Blue Cross Blue Shield etc, which use a similar data model to add information from their systems to the main computer. Since the last year the program has evolved from the ‘Mini’ phase and queries data with the aim to become a national resource.
“Sentinel has become an important part of our routine safety surveillance,” said Janet Woodcock, MD, Director of the FDA’s Center for Drug Evaluation and Research (CDER) at the annual Sentinel Initiative Public Workshop.
However, the truth of the matter is that the Sentinel has been successful in only implementing a small number of its expected actions. The Sentinel has still not become the active drug safety surveillance system it was slated to be, as it is still unable to detect unknown safety problems which may arise from some drugs.
“It’s very ambitious, and I congratulate everyone working on it,” Doris Peter, PhD, Director of Consumer Reports Best Buy Drugs Project, said at the annual Sentinel Initiative Public Workshop. “The original use case of finding [drug safety problems]… hasn’t been delivered on yet, and we don’t want the FDA to lose sight of that.”
Currently, the FDA uses Sentinel for two major tasks: rapid queries and active protocol-based queries. Every week the Sentinel provides one or two rapid queries which consist of statistical data e.g., the number of people from a certain age receiving a specific type of treatment. The FDA is provided with such queries on the basis of urgency within a few days.
“Many of these questions were unanswerable or would have taken months or years to answer previously,” Richard Platt, MD, MSc, Sentinel’s Principal Investigator and Executive Director of the Harvard Pilgrim Health Care Institute, said at the annual Sentinel Initiative Public Workshop.
In the same way the active protocol-based queries answer drug safety questions; however, the Sentinel is still not able to provide few substantial answers due to unavailability of data on new drugs. For example, in 2010, the FDA was unable to find intussusception risks associated with new a rotavirus vaccine called RotaTeq and Rotarix, but the risks were found in a clinical trial basis. The Sentinel is still working on 17 active protocol-based queries for the FDA.
The paper also highlights a majority of the FDA staff at CDER still do not have enough knowledge on how to use Sentinel and if it cannot even be understood, then its use would poses a problem. In the same way, some at CDER, which manages Sentinel, believe the program is not getting enough funding. Only $10 million to $15 million per year is allocated to the Sentinel at CDER, even though a full time staff works on the program. Likewise, even though the Center for Biologics Evaluation and Research also uses Sentinel but allocates a fund of just $5 million to $7 million for the program.
So far Sentinel has only provided two label changes and three safety communications, with diagnosis of no medical product withdrawals or recalls and is only used as an additional tool for major inquiries. The Sentinel may be a powerful tool but it is still stored in the toolbox of FDA, with 50% of safety label changes decided by old-fashioned sources.
One of the reasons why Sentinel is still not being used as a primary source is some of its findings are being questioned. For instance, in 2011 Sentinel analyzed data on a new anticoagulant called dabigatran and only found 19 cases of gastrointestinal bleeding. However, serious and fatal bleeding was reported on using the drug. Moreover, a meta-analysis of clinical trial found the drug had increased risk of bleeding.
“[The experience with dabigatran] teaches us something about the dawn of the era of electronic surveillance,” said Thomas Moore, Senior Scientist at the Institute for Safe Medication Practices. The system is not yet reliable enough to become a primary source or to identify unknown safety problems.”
Recently, the FDA outlined how they are working on making Sentinel better and broaden its abilities, so it can provide answers to drug safety questions. Another requirement of the Sentinel was to be able to detect whether a new device is safe for monitoring, but for the concept to become reality safety surveillance devices would need to have a unique device identifier (UDI). The FDA is still working on inserting and formulating the requirement outline of UDIs in monitoring devices.
“It’s a good thing that FDA has invested heavily in learning what we can do with electronic health records at the present time,” Moore said. “Unfortunately, the lesson is not nearly as much as we’d hoped.”