As a prelude to a fully operational real-time Sentinel System, FDA has established a mini Sentinel pilot to test scientific
methodologies for investigating drug use issues, explained Judy Racoosin, CDER's scientific lead for Sentinel. A main goal
set by FDAAA is to access data on at least 100 million individuals by July 1, 2012, building on its success in tapping into
drug use information on more than 25 million patients seen last July (see Pharm Exec, March 2010). FDA also has formed a drug surveillance collaboration with other federal agencies, including the Centers for
Medicaid and Medicare Services, the Veterans Administration, and the Department of Defense, to query these health data banks
on safety issues of mutual interest.
Over the past three years, Sentinel has established basic principles and policies, including a Common Data Model, core safety
surveillance methods, and Health Outcomes of Interest (HOIs) that deserve evaluation. A Sentinel Coordinating Center operated
by Richard Platt of the Harvard Pilgrim Healthcare Institute can send out queries to databases operated by Kaiser Permanente,
WellPoint, and the HMO Research Network, among others, and then evaluate resulting responses. Because the Sentinel Initiative
involves public health operations, as opposed to research, its query-and-analysis process can proceed without waiting for
institutional review board approval.
Sentinel will test several key protocols this year. One project will assess whether certain postmarketing regulatory initiatives
such as REMS (risk evaluation and mitigation strategies) enhance the safe use of medicines. An active surveillance project
is monitoring certain outcomes associated with rotavirus and human papillomavirus vaccines. An important study will examine
cardio events in users of diabetes drugs by comparing the incidence of myocardial infarction in patients prescribed saxagliptin
(Bristol-Myers Squibb's Onglyza) to those taking other diabetes treatments.
The importance of building a solid methodological foundation for interpreting results also was discussed at a symposium sponsored
by the Observational Medical Outcomes Partnership (OMOP), a collaboration of industry, FDA, and the Foundation for the NIH
(FNIH). OMOP is examining how well different methods and data sources can identify valid safety signals and whether meaningful
information can be gleaned from disparate observational data sources that use varying terminologies. The program has identified
ways to assess the strength of associations between drug exposure and specific adverse events, such as liver failure or bleeding,
and is examining the impact of missing patient information and how well alternative study designs can deal with variations
in patient demographics, comorbidities, and drug exposures.
OMOP's success in identifying methods and tools through an open, collaborative process has prompted the participants to extend
the partnership beyond its initial two-year time frame. The group also plans to expand into methods that could apply to medical
devices and biologics, in addition to drugs, and to assess approaches for CER and healthcare quality measures.
As Sentinel moves forward, sponsors and researchers are looking at the broader implications of dealing with early drug safety
signals in ways to avoid alarming the public. The mini Sentinel study on diabetes treatments and cardiac events, for example,
raises questions about when and how FDA will make public any findings, noted GlaxoSmithKline general counsel Daniel Troy at
the Sentinel workshop. Even if FDA says it won't release early results prior to full analysis, outside lawyers and policymakers
may try to compel disclosure, which could lead to liability for failure to warn. This applies not just to pharma companies,
but also to data partners that hold safety information in their systems, Troy pointed out.
Behrman acknowledged that liability is very much on the agency's mind because it could drive companies away from the Sentinel
project. Realistic expectations about what an active drug surveillance system can do is important, said Troy. Sentinel is
not the "be-all and end-all" information system, and FDA needs to make it clear to the public that Sentinel signals are based
on observational data, which has limitations in making informed judgments about medical safety issues.
Jill Wechsler is Pharmaceutical Executive's Washington correspondent. She can be reached at email@example.com