FDA Aims To Tap Sentinel Data Network For Drug Effectiveness Studies

New ‘Guardian’ program to monitor post-market effectiveness through the Sentinel electronic data network will take five years to build, FDA’s Woodcock says.

FDA is planning to develop ways of using its Sentinel electronic data network to conduct post-market studies on drug effectiveness in addition to the safety surveillance it is already being used for, Center for Drug Evaluation and Research Director Janet Woodcock announced.

The planned drug effectiveness research program is being called Guardian, Woodcock told the eighth annual Sentinel public workshop Feb. 3. The workshop was convened by the recently-formed Duke Margolis Center for Health Policy under Director Mark McClellan. McClellan, a former FDA commissioner and former CMS administrator, recently left the Brookings Institution to join the Duke organization.

With the drug effectiveness program, FDA expects to gain a more complete picture of the way drugs perform in the real world at a lower cost than is now possible with stand-alone epidemiology studies. Woodcock said FDA will work over the next five years to put together a system that can support randomized studies, observational studies, long-term cohort studies or registries to answer questions about effectiveness.

“We are at the very early stages of developing what we call the Guardian system,” Woodcock said. “Guardian would be a use of the Sentinel infrastructure for slightly different aims – to actively gather information about the performance of regulated medical products out in the health care system beyond the safety questions that are being asked Sentinel. And it would rely on the Sentinel infrastructure for part of its operations.”

Woodcock noted when a medical product reaches the market, “there are many, many unanswered questions about its use, not only about its safety performance but about its general performance and what populations it could be expanded to and what uses.” Safety involves a benefit-risk balance and “we need to be able rapidly and inexpensively to find out about the actual performance of the product both for ill and for good,” she pointed out.

“It’s really two sides of the same coin. We started with safety, that’s our statutory mandate but clearly there’s interest in generating evidence [on effectiveness] in a much more efficient manner than what we’re able to do now.”

In terms of the cost savings that could be achieved by using Sentinel, Woodcock explained: “the money we’ve put into Sentinel has been a substantial investment but nonetheless it is an enduring product, rather than these stand-alone studies which answered one question, or sometimes – not infrequently – you were left with a lot of unanswered questions after you spent the $10m and did a stand-alone epidemiology study.”

The agency also hopes its efforts to broaden the uses of the data network will lead the way for other stakeholders interested in leveraging Sentinel for effectiveness research.

“This would be our piece of what we foresee many parties doing, utilizing this infrastructure for various purposes,” Woodcock pointed out. “This would help us all. We’re constantly racked by questions about the performance of medical products that are answerable in a fast enough time to get the answers we need. And many of the parties and stakeholders in this audience have the same objectives.”

FDA has long promoted the idea that Sentinel could be used as a national resource by a variety of different stakeholders inside and outside the government as a way of establishing ongoing funding streams to support the program.

CDER devotes about $10m to $15m a year to Sentinel, Woodcock estimated. The Center for Biologics Evaluation and Research contributes another $5m to $8 m a year, CBER Office of Biostatistics and Epidemiology Director Steven Anderson said at the meeting. FDA is seeking continued funding for Sentinel through user fees as part of the Prescription Drug User Fee Act reauthorization process (Also see "PDUFA VI: FDA Proposes Expanding Sentinel, Real-World Safety Data Sources" - Pink Sheet, 18 Nov, 2015.).

A Five-Year Project

At this point, the Sentinel network has access to data, mainly from insurance company and health care system claims, covering 193 million individuals. The system also houses some electronic health records and recently expanded its reservoir of EHRs by bringing in the Hospital Corporation of America as a data partner. HCA includes a network of 168 hospitals and 113 surgery centers.

Over the past year, FDA has transitioned the management of Sentinel to the CDER Office of Safety and Epidemiology from the Office of Medical Policy as the program has matured and become part of the agency’s routine safety surveillance activities (Also see "FDA Sentinel Transition Will Involve Expanding Rx Safety Data Sources" - Pink Sheet, 23 Feb, 2015.).

The agency has also formed an Active Risk Identification and Analysis program (ARIA) within Sentinel that will continue to conduct post-market safety surveillance. The organizational move is designed to pave the way for moving Sentinel beyond its initial purpose to cover a range of additional applications, Woodcock explained.

One new use for the system in the safety arena might be to anticipate problems before a drug is approved, Office of Safety and Evaluation Director Gerald Dal Pan told the workshop. However, he emphasized that FDA staff will need to become much more familiar with Sentinel first.

“Within CDER, we really have to educate lots of people about what these data are and how they can use them,” Dal Pan pointed out.

“This isn’t just the province of a small group of epidemiologists and statisticians who focus on Sentinel all day… We’ve had to provide training to all our pharmacists who look at adverse event reports and to the physicians in the Office of New Drugs who are responsible for safety in review divisions so we can fully integrate this,” he explained.